Formulations for staphylococcus aureus vaccine

Abstract

NOT VISIBLE DUE TO STATUS OF PATENT

Description

FORMULATIONS FOR STAPHYLOCOCCUS AUREUS VACCINECROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No.: 63 / 620,746 filed on January 12, 2024 and U.S. Provisional Application No.: 63 / 620,747 filed on January 12, 2024, the disclosure of each of which is incorporated by reference herein in its entirety.SEQUENCE LISTING

[0002] This application contains an electronic Sequence Listing which has been submitted in XML file format with this application, the entire content of which is incorporated by reference herein in its entirety. The Sequence Listing XML file submitted with this application is entitled “14197-020-228_SEQLISTING.xml”, was created on January 8, 2025, and is 79,113 bytes in size.GOVERNMENT LICENSE RIGHTS

[0003] This invention was made with government support under IDSEP160030-02-00 awarded by Department of Health and Human Services, Administration for Strategic Preparedness and Response (HHS / ASPR). The government has certain rights in the invention.1. FIELD

[0004] The present invention relates to lyophilized and spray freeze-dried formulations of Staphylococcus aureus vaccine, which have comparable biophysical attributes as the liquid formulation, and have long-term stability.2. BACKGROUND OF THE INVENTION

[0005] Staphylococcus aureus is the leading cause of skin and soft tissue infections (SSTIs) in the U.S. as well as more serious invasive diseases, including bacteremia, sepsis, endocarditis, surgical site infections, osteomyelitis, and pneumonia. These infections are exacerbated by the emergence of antibiotic-resistant clinical isolates such as methicillin-resistant S. aureus (MRSA), highlighting the need for alternatives to antibiotics to treat bacterial infections. We have previously developed a multi-component toxoid vaccine (LTB-SA7, also referred as IBT-V02) in a liquid formulation with efficacy against multiple strains of Staphylococcus aureus prevalent in the industrialized world (Karauzum 2021, Front Immunol.; 12:624310). However, liquid vaccineformulations are not compatible with the paucity of cold chain storage infrastructure in many low-to-middle income countries (LMICs).3. SUMMARY OF THE INVENTION

[0006] The present disclosure is directed to lyophilized and spray freeze-dried formulations of Staphylococcus aureus vaccine. Both formulations have comparable biophysical attributes as the liquid formulation, and have long-term stability. The lyophilized and spray freeze-dried formulations of Staphylococcus aureus vaccine (e.g. LTB-SA7 vaccine) provided herein are effective alternative to liquid vaccine formulations of Staphylococcus aureus vaccine (e.g. LTB- SA7 vaccine) against S. aureus infections, which has important implications for vaccination of patients from LMICs.

[0007] In one aspect, provided herein is a lyophilized pharmaceutical composition comprising: (1) a multicomponent vaccine, (2) a buffer, (3) sucrose, and (4) polysorbate 80, wherein the multicomponent vaccine comprises: HlaH35LH48L, LukSmut9, LukFmuti, TBA225 and LukABmutso .

[0008] In some embodiments of the lyophilized pharmaceutical composition provided herein, the composition further comprises histidine-borate.

[0009] In some embodiments of the lyophilized pharmaceutical composition provided herein, the buffer is phosphate buffer.

[0010] In some embodiments of the lyophilized pharmaceutical composition provided herein, Hlau35LH48L comprises a Hla toxoid with H35L and H48L mutations, or comprises the amino acid sequence of SEQ ID NO: 1; LukSmut9 comprises the S subunit of a PVL toxoid with T28F, K97A, and S209A mutations, or comprises the amino acid sequence of SEQ ID NO: 2; LukFmuti comprises the F subunit of a PVL toxoid with K102A mutation, or comprises the amino acid sequence of SEQ ID NO: 3; LukABmutso comprises a dimeric toxoid form of LukAB with D39A mutation in LukA and R23E mutation in LukB, or comprises a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO:5; TBA225 comprises a fusion protein comprising: (1) a TSST-1 toxoid with L30R, D27A, and I46A mutations, (2) a SEB toxoid with L45R, Y89A, and Y94A mutations, and (2) a SEA toxoid with L48R, D70R, Y92A, and H225A mutations; or comprising the amino acid sequence of SEQ ID NO: 6.

[0011] In some embodiments of the lyophilized pharmaceutical composition provided herein, HlaH35LH48L consists of the amino acid sequence of SEQ ID NO: 1; LukSmut9 consists of the amino acid sequence of SEQ ID NO: 2; LukFmutl consists of the amino acid sequence of SEQ ID NO: 3; LukABmut50 comprises a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5; and TBA225 consists of the amino acid sequence of SEQ ID NO: 6.

[0012] In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about from 0.005 mg / ml to 10 mg / ml after reconstitution in a liquid formulation.

[0013] In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is about from 0.001 mg / ml to 2 mg / ml after reconstitution in a liquid formulation.

[0014] In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of sucrose is about from 2% (weight / volume, 20 g / L) to 10% (weight / volume, 100 g / L) after reconstitution in a liquid formulation.

[0015] In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of polysorbate 80 is about from 0.004% (weight / volume, 0.04 g / L) to 2% (weight / volume, 20 g / L) after reconstitution in a liquid formulation.

[0016] In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of histidine-borate is about from O.lmM to 25mM after reconstitution in a liquid formulation.

[0017] In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of phosphate buffer is about from 0.5mM to 20mM after reconstitution in a liquid formulation.

[0018] In some embodiments of the lyophilized pharmaceutical composition provided herein, the lyophilized pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 2: 400: 1 by weight. In some embodiments of the lyophilized pharmaceutical composition provided herein, the lyophilized pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 1 : 400: 1 by weight. In some embodiments of the lyophilized pharmaceutical composition provided herein, the lyophilized pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80at about a ratio of 0.5: 400: 1 by weight. In some embodiments of the lyophilized pharmaceutical composition provided herein, the lyophilized pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 0.125: 400: 1 by weight. In some embodiments of the lyophilized pharmaceutical composition provided herein, the lyophilized pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 0.03125: 400: 1 by weight.

[0019] In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein is about 0.4 mg / ml, the concentration of the histidine-borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of the polysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5 after reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein is about 0.2 mg / ml, the concentration of the histidine-borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of the polysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5 after reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein is about 0.1 mg / ml, the concentration of the histidine-borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of the polysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5 after reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein is about 0.025 mg / ml, the concentration of the histidine-borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of the polysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5 after reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein is about 0.00625 mg / ml, the concentration of the histidine-borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of thepolysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5 after reconstitution in a liquid formulation.

[0020] In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein is about 200 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 40pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein is about 50 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 10 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein is about 12.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 2.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein is about 3.125 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 0.625 pg per dose.

[0021] In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein is 200 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 40pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein is 50 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 10 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein is 12.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 2.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein is 3.125 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 0.625 pg per dose.

[0022] In some embodiments of the lyophilized pharmaceutical composition provided herein, the multivalent vaccine has less than 15%, 10%, 5%, or 2% protein aggregation or degradation compared with a multivalent vaccine with the same components that is formulated at the same concentration in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the multivalent vaccine has at least about 2%, at least about 5%, atleast about 10%, at least about 15%, at least about 20%, at least about 25%, or at least about 50% less protein aggregation or degradation compared with a multivalent vaccine with the same composition that is formulated at the same concentration in a liquid formulation.

[0023] In some embodiments of the lyophilized pharmaceutical composition provided herein, the protein aggregation or degradation is measured by SEC-HPLC, SDS-PAGE or Western blot assay.

[0024] In some embodiments of the lyophilized pharmaceutical composition provided herein, the multivalent vaccine has similar immunogenic activity compared with a multivalent vaccine with the same components that is formulated at the same concentration in a liquid formulation.

[0025] In some embodiments of the lyophilized pharmaceutical composition provided herein, the immunogenic activity is measured by the levels of antibody titers production in a subject induced by administering to the subject the multivalent vaccine in a lyophilized or liquid formulation. In some embodiments, the immunogenic activity of the multivalent vaccine is measured by the immune respone elicted by the the multivalent vaccine in a subject. In some embodiments, the immunogenic activity of the multivalent vaccine can be assessed by measuring the B-cell response induced by the multivalent vaccine. In some embodiments, the immunogenic activity of the multivalent vaccine can be assessed by measuring the T-cell mediated protection against S. aureus infection induced by the multivalent vaccine.

[0026] In some embodiments of the lyophilized pharmaceutical composition provided herein, the increase in the amount of aggregated or degraded protein in the composition is less than 15%, 10%, 5%, or 2% after storage at -20°C for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.

[0027] In some embodiments of the lyophilized pharmaceutical composition provided herein, the increase in the amount of aggregated or degraded protein in the composition is less than 15%, 10%, 5%, or 2% after storage at room temperature (RT) for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.

[0028] In some embodiments of the lyophilized pharmaceutical composition provided herein, the increase in the amount of aggregated or degraded protein in the composition is less than 15%, 10%, 5%, or 2% after storage at 30°C for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.

[0029] In some embodiments of the lyophilized pharmaceutical composition provided herein, the multivalent vaccine retains at least 70% , 80%, 90% or 95% of its initial immunogenic activity after storage at -20°C for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.

[0030] In some embodiments of the lyophilized pharmaceutical composition provided herein, the multivalent vaccine retains at least 70% , 80%, 90% or 95% of its initial immunogenic activity after storage at RT for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.

[0031] In some embodiments of the lyophilized pharmaceutical composition provided herein, the multivalent vaccine retains at least 70% , 80%, 90% or 95% of its initial immunogenic activity after storage at 30°C for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.

[0032] In another aspect, provided herein is a method of generating the lyophilized pharmaceutical composition provided herein, comprising: (1) dissolving the multicomponent vaccine, sucrose, and polysorbate 80 in a suitable solvent to form a liquid composition; (2) freezing the liquid composition to form a frozen composition; (3) drying the frozen composition under a primary reduced pressure at a primary drying temperate for a period of time effective to reduce the moisture content of the composition; and (4) further drying the frozen composition under a second reduced pressure at a second drying temperature for a period of time effective to further reduce the moisture content of the composition, thereby producing the lyophilized composition.

[0033] In some embodiments provided herein, the method comprises: (1) dissolving the multicomponent vaccine, sucrose, and polysorbate 80 in a suitable solvent to form a liquid composition; (2) freezing the liquid composition at -40°C for 2 hours to form a frozen composition; annealing the frozen composition at -25°C for 2 hours; and further freezing the frozen composition at -40°C for 1 hour; (3) drying the frozen composition under a primary reduced pressure at -40°C for 0.5 hour to reduce the moisture content of the composition; and (4) further drying the frozen composition under a second reduced pressure at 10°C for 1 hour to further reduce the moisture content of the composition, thereby producing the lyophilized composition. In some embodiments, the primary reduced pressure is the same as the second reduced pressure. In some embodiments, the pressure of the lyophilization chamber for all drying stage is set at 50mTorr.

[0034] In some embodiments provided herein, the lyophilized pharmaceutical composition has a final moisture content of between 3% and 5%.

[0035] In another aspect, provided herein is spray freeze-dried pharmaceutical composition comprising: (1) a multicomponent vaccine, (2) a buffer, (3) sucrose, and (4) polysorbate 80, wherein the multicomponent vaccine comprises: HlaH35LH48L, LukSmut9, LukFmuti, TBA225 and LukABmutso .

[0036] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the composition further comprises histidine-borate.

[0037] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the buffer is phosphate buffer.

[0038] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, EHaH35LH48L comprises a Hla toxoid with H35L and H48L mutations, or comprises the amino acid sequence of SEQ ID NO: 1; LukSmut9 comprises the S subunit of a PVL toxoid with T28F, K97A, and S209A mutations, or comprises the amino acid sequence of SEQ ID NO: 2; LukFmuti comprises the F subunit of a PVL toxoid with K102A mutation, or comprises the amino acid sequence of SEQ ID NO: 3; LukABmutso comprises a dimeric toxoid form of LukAB with D39A mutation in LukA and R23E mutation in LukB, or comprises a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO:5; TBA225 comprises a fusion protein comprising: a TSST-1 toxoid with L30R, D27A, and I46A mutations, a SEB toxoid with L45R, Y89A, and Y94A mutations, and a SEA toxoid with L48R, D70R, Y92A, and H225A mutations; or comprising the amino acid sequence of SEQ ID NO: 6.

[0039] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, EHaH35LH48L consists of the amino acid sequence of SEQ ID NO: 1; LukSmut9 consists of the amino acid sequence of SEQ ID NO: 2; LukFmuti consists of the amino acid sequence of SEQ ID NO: 3; LukABmut50 comprises a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5; and TBA225 consists of the amino acid sequence of SEQ ID NO: 6.

[0040] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about from 0.005 mg / ml to 10 mg / ml after reconstitution in a liquid formulation.

[0041] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is about from 0.001 mg / ml to 2 mg / ml after reconstitution in a liquid formulation.

[0042] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of sucrose is from 2% (weight / volume, 20 g / L) to 10% (weight / volume, 100 g / L) after reconstitution in a liquid formulation.

[0043] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of polysorbate 80 is about from 0.004% (weight / volume, 0.04 g / L) to 2% (weight / volume, 20 g / L) after reconstitution in a liquid formulation.

[0044] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of histidine-borate is about from O.lmM to 25mM after reconstitution in a liquid formulation.

[0045] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of phosphate buffer is about from 0.5mM to 20mM after reconstitution in a liquid formulation.

[0046] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the spray freeze-dried pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 2: 400: 1 by weight. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the spray freeze-dried pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 1 : 400: 1 by weight. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the spray freeze-dried pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 0.5: 400: 1 by weight. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the spray freeze-dried pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 0.125: 400: 1 by weight. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the spray freeze-dried pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 0.03125: 400: 1 by weight.

[0047] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein is about 0.4 mg / ml, the concentration of the histidine-borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of the polysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5 after reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein is about 0.2 mg / ml, the concentration of the histidine-borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of the polysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5 after reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein is about 0.1 mg / ml, the concentration ofthe histidine-borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of the polysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5 after reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein is about 0.025 mg / ml, the concentration of the histidine-borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of the polysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5 after reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein is about 0.00625 mg / ml, the concentration of the histidine-borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of the polysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5 after reconstitution in a liquid formulation.

[0048] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein is about 200 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 40pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein is about 50 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 10 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein is about 12.5 pg per dose. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, each component of the vaccine is about 2.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein is about 3.125 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 0.625 pg per dose.

[0049] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein is 200 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 40pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, thetotal protein is 50 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 10 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein is 12.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 2.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein is 3.125 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 0.625 pg per dose.

[0050] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the multivalent vaccine has less than 15%, 10%, 5%, or 2% protein aggregation or degradation compared with a multivalent vaccine with the same components that is formulated at the same concentration in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the multivalent vaccine has at least about 2%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, or at least about 50% less protein aggregation or degradation compared with a multivalent vaccine with the same composition that is formulated at the same concentration in a liquid formulation.

[0051] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the protein aggregation or degradation is measured by SEC-HPLC, SDS-PAGE or Western blot assay.

[0052] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the multivalent vaccine has similar immunogenic activity compared with a multivalent vaccine with the same components that is formulated at the same concentration in a liquid formulation.

[0053] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the immunogenic activity is measured by the levels of antibody titers production in a subject induced by administering to the subject the multivalent vaccine in a spray freeze-dried or liquid formulation.

[0054] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the increase in the amount of aggregated or degraded protein in the composition is less than 15%, 10%, 5%, or 2% after storage at -20°C for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months,about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.

[0055] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the increase in the amount of aggregated or degraded protein in the composition is less than 15%, 10%, 5%, or 2% after storage at RT for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.

[0056] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the increase in the amount of aggregated or degraded protein in the composition is less than 15%, 10%, 5%, or 2% after storage at 30°C for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.

[0057] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the multivalent vaccine retains at least 70%, 80%, 90% or 95% of its initial immunogenic activity after storage at -20°C for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.

[0058] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the multivalent vaccine retains at least 70%, 80%, 90% or 95% of its initial immunogenic activity after storage at room temperature (RT) for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.

[0059] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the multivalent vaccine retains at least 70% , 80%, 90% or 95% of its initial immunogenic activity after storage at 30°C for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.

[0060] In another aspect, provided herein is a method of generating the spray freeze-dried pharmaceutical composition, comprising: dissolving the multicomponent vaccine, histidineborate, phosphate buffer, sucrose, and polysorbate 80 in a suitable solvent to form a liquid composition; atomizing the liquid formulation into specifically sized spherical droplets; immediately freezing the droplets and locking in the size and shape of each individual particle; collecting the particles and drying the particles in bulk in a lyophilization chamber.

[0061] In another aspect, provided herein is a reconstituted pharmaceutical composition comprising: (1) a multicomponent vaccine, (2) a buffer, (3) sucrose, (4) polysorbate 80, and (5) a reconstitution liquid, wherein the multicomponent vaccine comprises: EHaH35LH48L, LukSmut9, LukFmuti, TBA225 and LukABmutso.

[0062] In some embodiments of the reconstituted pharmaceutical composition provided herein, the composition further comprises histidine-borate.

[0063] In some embodiments of the reconstituted pharmaceutical composition provided herein, the buffer is phosphate buffer.

[0064] In some embodiments of the reconstituted pharmaceutical composition provided herein, EHaH35LH48L comprises a Hla toxoid with H35L and H48L mutations, or comprises the amino acid sequence of SEQ ID NO: 1; LukSmut9 comprises the S subunit of a PVL toxoid with T28F, K97A, and S209A mutations, or comprises the amino acid sequence of SEQ ID NO: 2; LukFmuti comprises the F subunit of a PVL toxoid with K102A mutation, or comprises the amino acid sequence of SEQ ID NO: 3; LukABmutso comprises a dimeric toxoid form of LukAB with D39A mutation in LukA and R23E mutation in LukB, or comprises a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO:5; TBA225 comprises a fusion protein comprising: (1) a TSST-1 toxoid with L30R, D27A, and I46A mutations, (2) a SEB toxoid with L45R, Y89A, andY94A mutations, and (3) a SEA toxoid with L48R, D70R, Y92A, and H225A mutations; or comprising the amino acid sequence of SEQ ID NO: 6.

[0065] In some embodiments of the reconstituted pharmaceutical composition provided herein, HlaH35LH48L consists of the amino acid sequence of SEQ ID NO: 1; LukSmut9 consists of the amino acid sequence of SEQ ID NO: 2; LukFmuti consists of the amino acid sequence of SEQ ID NO: 3; LukABmutso comprises a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5; and TBA225 consists of the amino acid sequence of SEQ ID NO: 6.

[0066] In some embodiments of the reconstituted pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about from 0.005 mg / ml to 10 mg / ml.

[0067] In some embodiments of the reconstituted pharmaceutical composition provided herein, the concentration of each component of the vaccine is about from 0.001 mg / ml to 2 mg / ml.

[0068] In some embodiments of the reconstituted pharmaceutical composition provided herein, the concentration of sucrose is about from 2% (weight / volume, 20 g / L) to 10% (weight / volume, 100 g / L).

[0069] In some embodiments of the reconstituted pharmaceutical composition provided herein, the concentration of polysorbate 80 is about from 0.004% (weight / volume, 0.04 g / L) to 2% (weight / volume, 20 g / L).

[0070] In some embodiments of the reconstituted pharmaceutical composition provided herein, the concentration of histidine-borate is about from O.lmM to 25mM.

[0071] In some embodiments of the reconstituted pharmaceutical composition provided herein, the concentration of phosphate buffer is about from 0.5mM to 20mM.

[0072] In some embodiments of the reconstituted pharmaceutical composition provided herein, the reconstituted pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 2: 400: 1 by weight. In some embodiments of the reconstituted pharmaceutical composition provided herein, the reconstituted pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 1 : 400: 1 by weight. In some embodiments of the reconstituted pharmaceutical composition provided herein, the reconstituted pharmaceutical composition comprises the total protein, sucrose, and polysorbate80 at about a ratio of 0.5: 400: 1 by weight. In some embodiments of the reconstituted pharmaceutical composition provided herein, the reconstituted pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 0.125: 400: 1 by weight. In some embodiments of the reconstituted pharmaceutical composition provided herein, the reconstituted pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 0.03125: 400: 1 by weight.

[0073] In some embodiments of the reconstituted pharmaceutical composition provided herein, the concentration of the total protein is about 0.4 mg / ml, the concentration of the histidine-borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of the polysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5. In some embodiments of the reconstituted pharmaceutical composition provided herein, the concentration of the total protein is about 0.2 mg / ml, the concentration of the histidine-borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of the polysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5. In some embodiments of the reconstituted pharmaceutical composition provided herein, the concentration of the total protein is about 0.1 mg / ml, the concentration of the histidine-borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of the polysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5. In some embodiments of the reconstituted pharmaceutical composition provided herein, the concentration of the total protein is about 0.025 mg / ml, the concentration of the histidine-borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of the polysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5. In some embodiments of the reconstituted pharmaceutical composition provided herein, the concentration of the total protein is about 0.00625 mg / ml, the concentration of the histidine-borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of the polysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5.

[0074] In some embodiments of the reconstituted pharmaceutical composition provided herein, the total protein is about 200 pg per dose. In some embodiments of the reconstituted pharmaceutical composition provided herein, each component of the vaccine is about 40pg per dose. In some embodiments of the reconstituted pharmaceutical composition provided herein, the total protein is about 50 pg per dose. In some embodiments of the reconstituted pharmaceutical composition provided herein, each component of the vaccine is about 10 pg per dose. In some embodiments of the reconstituted pharmaceutical composition provided herein, the total protein is about 12.5 pg per dose. In some embodiments of the reconstituted pharmaceutical composition provided herein, each component of the vaccine is about 2.5 pg per dose. In some embodiments of the reconstituted pharmaceutical composition provided herein, the total protein is about 3.125 pg per dose. In some embodiments of the reconstituted pharmaceutical composition provided herein, each component of the vaccine is about 0.625 pg per dose.

[0075] In some embodiments of the reconstituted pharmaceutical composition provided herein, the total protein is 200 pg per dose. In some embodiments of the reconstituted pharmaceutical composition provided herein, each component of the vaccine is 40pg per dose. In some embodiments of the reconstituted pharmaceutical composition provided herein, the total protein is 50 pg per dose. In some embodiments of the reconstituted pharmaceutical composition provided herein, each component of the vaccine is 10 pg per dose. In some embodiments of the reconstituted pharmaceutical composition provided herein, the total protein is 12.5 pg per dose. In some embodiments of the reconstituted pharmaceutical composition provided herein, each component of the vaccine is 2.5 pg per dose. In some embodiments of the reconstituted pharmaceutical composition provided herein, the total protein is 3.125 pg per dose. In some embodiments of the reconstituted pharmaceutical composition provided herein, each component of the vaccine is 0.625 pg per dose.

[0076] In another aspect, provided herein is a method of treating or preventing Staphylococcus aureus (SA) infection in a subject, comprising administering to the subject the reconstituted pharmaceutical composition provided herein.

[0077] In some embodiments of the method provided herein, the subject is a human subject.

[0078] In another aspect, provided herein is a composition suitable for lyophilization or spray-freeze drying, comprising: (1) a multicomponent vaccine, (2) a buffer, (3) sucrose, and (4)polysorbate 80, wherein the multicomponent vaccine comprises: HlamsuwsL, LukSmut9, LukFmuti, TBA225 and LukABmutso.

[0079] In some embodiments of the composition suitable for lyophilization or spray -freeze drying provided herein, the composition further comprises histidine-borate.

[0080] In some embodiments of the composition suitable for lyophilization or spray -freeze drying provided herein, the buffer is phosphate buffer.

[0081] In some embodiments of the composition suitable for lyophilization or spray -freeze drying provided herein, the concentration of the total protein is about 0.4 mg / ml, the concentration of the histidine-borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of the polysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5. In some embodiments of the composition suitable for lyophilization or spray -freeze drying provided herein, the concentration of the total protein is about 0.2 mg / ml, the concentration of the histidine-borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of the polysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5 after reconstitution in a liquid formulation. In some embodiments of the composition suitable for lyophilization or spray -freeze drying provided herein, the concentration of the total protein is about 0.1 mg / ml, the concentration of the histidine-borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of the polysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5 after reconstitution in a liquid formulation. In some embodiments of the composition suitable for lyophilization or spray-freeze drying provided herein, the concentration of the total protein is about 0.025 mg / ml, the concentration of the histidine-borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of the polysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5 after reconstitution in a liquid formulation. In some embodiments of the composition suitable for lyophilization or spray -freeze drying provided herein, the concentration of the total protein is about 0.00625 mg / ml, the concentration of the histidine- borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of thepolysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5 after reconstitution in a liquid formulation.

[0082] In some embodiments of the composition suitable for lyophilization or spray -freeze drying provided herein, the total protein is about 200 pg per dose. In some embodiments of the composition suitable for lyophilization or spray -freeze drying provided herein, each component of the vaccine is about 40pg per dose. In some embodiments of the composition suitable for lyophilization or spray-freeze drying provided herein, the total protein is about 50 pg per dose. In some embodiments of the composition suitable for lyophilization or spray -freeze drying provided herein, each component of the vaccine is about 10 pg per dose. In some embodiments of the composition suitable for lyophilization or spray -freeze drying provided herein, the total protein is about 12.5 pg per dose. In some embodiments of the composition suitable for lyophilization or spray-freeze drying provided herein, each component of the vaccine is about2.5 pg per dose. In some embodiments of the composition suitable for lyophilization or sprayfreeze drying provided herein, the total protein is about 3.125 pg per dose. In some embodiments of the composition suitable for lyophilization or spray -freeze drying provided herein, each component of the vaccine is about 0.625 pg per dose.

[0083] In some embodiments of the composition suitable for lyophilization or spray -freeze drying provided herein, the total protein is 200 pg per dose. In some embodiments of the composition suitable for lyophilization or spray -freeze drying provided herein, each component of the vaccine is 40pg per dose. In some embodiments of the composition suitable for lyophilization or spray-freeze drying provided herein, the total protein is 50 pg per dose. In some embodiments of the composition suitable for lyophilization or spray-freeze drying provided herein, each component of the vaccine is 10 pg per dose. In some embodiments of the composition suitable for lyophilization or spray-freeze drying provided herein, the total protein is12.5 pg per dose. In some embodiments of the composition suitable for lyophilization or sprayfreeze drying provided herein, each component of the vaccine is 2.5 pg per dose. In some embodiments of the composition suitable for lyophilization or spray -freeze drying provided herein, the total protein is 3.125 pg per dose. In some embodiments of the composition suitable for lyophilization or spray-freeze drying provided herein, each component of the vaccine is 0.625 pg per dose.

[0084] In another aspect, provided herein is a kit comprising one or more containers and instructions for use, wherein the one or more containers comprise the pharmaceutical composition provided herein.3.1 ILLUSTRATIVE EMBODIMENTS1. A lyophilized pharmaceutical composition comprising: a. a multicomponent vaccine, b. a buffer, c. sucrose, and d. polysorbate 80, wherein the multicomponent vaccine comprises: EHaH35LH48L, LukSmut9, LukFmuti, TBA225 and LukABmutso.2. The lyophilized pharmaceutical composition of paragraph 1, wherein the composition further comprises histidine-borate.3. The lyophilized pharmaceutical composition of paragraph 1 or 2, wherein the buffer is phosphate buffer.4. The lyophilized pharmaceutical composition of any one of paragraphs 1 to 3, wherein a. HlaH35LH48L comprises a Hla toxoid with H35L and H48L mutations, or comprises the amino acid sequence of SEQ ID NO: 1; b. LukSmut9 comprises the S subunit of a PVL toxoid with T28F, K97A, and S209A mutations, or comprises the amino acid sequence of SEQ ID NO: 2; c. LukFmuti comprises the F subunit of a PVL toxoid with K102A mutation, or comprises the amino acid sequence of SEQ ID NO: 3; d. LukABmutso comprises a dimeric toxoid form of LukAB with D39A mutation in LukA and R23E mutation in LukB, or comprises a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5; e. TBA225 comprises a fusion protein comprising: i. a TSST-1 toxoid with L30R, D27A, and 146 A mutations, ii. a SEB toxoid with L45R, Y89A, and Y94A mutations, and iii. a SEA toxoid with L48R, D70R, Y92A, and H225A mutations; orcomprising the amino acid sequence of SEQ ID NO: 6;5. The lyophilized pharmaceutical composition of paragraph 4, wherein a. Hlau35LH48L consists of the amino acid sequence of SEQ ID NO: 1; b. LukSmut9 consists of the amino acid sequence of SEQ ID NO: 2; c. LukFmuti consists of the amino acid sequence of SEQ ID NO: 3; d. LukABmutso comprises a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5; and e. TBA225 consists of the amino acid sequence of SEQ ID NO: 6.6. The lyophilized pharmaceutical composition of any one of paragraphs 1 to 5, wherein the concentration of the total protein of the vaccine is about from 0.005 mg / ml to 10 mg / ml after reconstitution in a liquid formulation.7. The lyophilized pharmaceutical composition of any one of paragraphs 1 to 6, wherein the concentration of each component of the vaccine is about from 0.001 mg / ml to 2 mg / ml after reconstitution in a liquid formulation.8. The lyophilized pharmaceutical composition of any one of paragraphs 1 to 7, wherein the concentration of sucrose is about from 2% (weight / volume, 20 g / L) to 10% (weight / volume, 100 g / L) after reconstitution in a liquid formulation.9. The lyophilized pharmaceutical composition of any one of paragraphs 1 to 8, wherein the concentration of polysorbate 80 is about from 0.004% (weight / volume, 0.04 g / L) to 2% (weight / volume, 20 g / L) after reconstitution in a liquid formulation.10. The lyophilized pharmaceutical composition of any one of paragraphs 1 to 7, wherein the concentration of histidine-borate is about from O.lmM to 25mM after reconstitution in a liquid formulation.11. The lyophilized pharmaceutical composition of any one of paragraphs 3 to 10, wherein the concentration of phosphate buffer is about from 0.5mM to 20mM after reconstitution in a liquid formulation.12. The lyophilized pharmaceutical composition of any one of paragraphs 1 to 5, wherein the lyophilized pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 2: 400: 1 by weight.13. The lyophilized pharmaceutical composition of any one of paragraphs 1 to 11, wherein the concentration of the total protein is about 0.4 mg / ml (0.2mg per dose), the concentration of the histidine-borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of the polysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5 after reconstitution in a liquid formulation.14. The lyophilized pharmaceutical composition of any one of paragraphs 1 to 9, wherein the total protein is about 200 pg per dose.15. The lyophilized pharmaceutical composition of any one of paragraphs 1 to 12, wherein the multivalent vaccine has at least about 2%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, or at least about 50% less protein aggregation or degradation compared with a multivalent vaccine with the same composition that is formulated at the same concentration in a liquid formulation.16. The lyophilized pharmaceutical composition of paragraph 15, wherein the protein aggregation or degradation is measured by SEC-HPLC, SDS-PAGE or Western blot assay.17. The lyophilized pharmaceutical composition of any one of paragraphs 1 to 14, wherein the multivalent vaccine has similar immunogenic activity compared with a multivalent vaccine with the same components that is formulated at the same concentration in a liquid formulation.18. The lyophilized pharmaceutical composition of paragraph 17, wherein the immunogenic activity is measured by the levels of antibody titers production in a subject induced by administering to the subject the multivalent vaccine in a lyophilized or liquid formulation.19. The lyophilized pharmaceutical composition of any one of paragraphs 1 to 18, wherein the increase in the amount of aggregated or degraded protein in the composition is less than 15%, 10%, 5%, or 2% after storage at -20°C for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.20. The lyophilized pharmaceutical composition of any one of paragraphs 1 to 18, wherein the increase in the amount of aggregated or degraded protein in the composition is lessthan 15%, 10%, 5%, or 2% after storage at 30°C for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.21. The lyophilized pharmaceutical composition of any one of paragraphs 1 to 18, wherein the multivalent vaccine retains at least 70% , 80%, 90% or 95% of its initial immunogenic activity after storage at -20°C for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.22. The lyophilized pharmaceutical composition of any one of paragraphs 1 to 18, wherein the multivalent vaccine retains at least 70% , 80%, 90% or 95% of its initial immunogenic activity after storage at 30°C for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.23. A method of generating the lyophilized pharmaceutical composition of any one of paragraphs 1 to 22, comprising: a. dissolving the multicomponent vaccine, sucrose, and polysorbate 80 in a suitable solvent to form a liquid composition; b. freezing the liquid composition to form a frozen composition; c. drying the frozen composition under a primary reduced pressure at a primary drying temperate for a period of time effective to reduce the moisture content of the composition; and d. further drying the frozen composition under a second reduced pressure at a second drying temperature for a period of time effective to further reduce the moisture content of the composition, thereby producing the lyophilized composition.24. The method of paragraph 23, wherein the method comprises:a. dissolving the multicomponent vaccine, sucrose, and polysorbate 80 in a suitable solvent to form a liquid composition; b. freezing the liquid composition at -40°C for 2 hours to form a frozen composition; annealing the frozen composition at -25°C for 2 hours; and further freezing the frozen composition at -40°C for 1 hour. c. drying the frozen composition under a primary reduced pressure at -40°C for 0.5 hour to reduce the moisture content of the composition; and d. further drying the frozen composition under a second reduced pressure at 10°C for 1 hour to further reduce the moisture content of the composition, thereby producing the lyophilized composition.25. The method of paragraph 23 or 24, wherein the lyophilized pharmaceutical composition has a final moisture content of between 3% and 5%.26. A spray freeze-dried pharmaceutical composition comprising: a. a multicomponent vaccine, b. a buffer, c. sucrose, and d. polysorbate 80, wherein the multicomponent vaccine comprises: EHaH35LH48L, LukSmut9, LukFmuti, TBA225 and LukABmutso.27. The spray freeze-dried pharmaceutical composition of paragraph 26, wherein the composition further comprises histidine-borate.28. The spray freeze-dried pharmaceutical composition of paragraph 26 or 27, wherein the buffer is phosphate buffer.29. The spray freeze-dried pharmaceutical composition of any one of paragraphs 26 to 28, wherein: a. Hlau35LH48L comprises a Hla toxoid with H35L and H48L mutations, or comprises the amino acid sequence of SEQ ID NO: 1; b. LukSmut9 comprises the S subunit of a PVL toxoid with T28F, K97A, and S209A mutations, or comprises the amino acid sequence of SEQ ID NO: 2; c. LukFmuti comprises the F subunit of a PVL toxoid with K102A mutation, or comprises the amino acid sequence of SEQ ID NO: 3;d. LukABmutso comprises a dimeric toxoid form of LukAB with D39A mutation in LukA and R23E mutation in LukB, or comprises a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5; e. TBA225 comprises a fusion protein comprising: i. a TSST-1 toxoid with L30R, D27A, and 146 A mutations, ii. a SEB toxoid with L45R, Y89A, and Y94A mutations, and iii. a SEA toxoid with L48R, D70R, Y92A, and H225A mutations; or comprising the amino acid sequence of SEQ ID NO: 6.30. The spray freeze-dried pharmaceutical composition of paragraph 29, wherein: a. Hlau35LH48L consists of the amino acid sequence of SEQ ID NO: 1; b. LukSmut9 consists of the amino acid sequence of SEQ ID NO: 2; c. LukFmuti consists of the amino acid sequence of SEQ ID NO: 3; d. LukABmutso comprises a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5; and e. TBA225 consists of the amino acid sequence of SEQ ID NO: 6.31. The spray freeze-dried pharmaceutical composition of any one of paragraphs 26 to 30, wherein the concentration of the total protein of the vaccine is about from 0.005 mg / ml to 10 mg / ml after reconstitution in a liquid formulation.32. The spray freeze-dried pharmaceutical composition of any one of paragraphs 26 to 31, wherein the concentration of each component of the vaccine is about from 0.001 mg / ml to 2 mg / ml after reconstitution in a liquid formulation.33. The spray freeze-dried pharmaceutical composition of any one of paragraphs 26 to 32, wherein the concentration of sucrose is from 2% (weight / volume, 20 g / L) to 10% (weight / volume, 100 g / L) after reconstitution in a liquid formulation.34. The spray freeze-dried pharmaceutical composition of any one of paragraphs 26 to 33, wherein the concentration of polysorbate 80 is about from 0.004% (weight / volume, 0.04 g / L) to 2% (weight / volume, 20 g / L) after reconstitution in a liquid formulation.35. The spray freeze-dried pharmaceutical composition of any one of paragraphs 27 to 32, wherein the concentration of histidine-borate is about from O.lmM to 25mM after reconstitution in a liquid formulation.36. The spray freeze-dried pharmaceutical composition of any one of paragraphs 28 to 35, wherein the concentration of phosphate buffer is about from 0.5mM to 20mM after reconstitution in a liquid formulation.37. The spray freeze-dried pharmaceutical composition of any one of paragraphs 26 to 36, wherein the spray freeze-dried pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at the ratio of 2: 400: 1 in weight.38. The spray freeze-dried pharmaceutical composition of any one of paragraphs 28 to 36, wherein the concentration of the total protein is about 0.4 mg / ml (0.2 mg per dose), the concentration of the histidine-borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of the polysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5 after reconstitution in a liquid formulation.39. The spray freeze-dried pharmaceutical composition of any one of paragraphs 28 to 36, wherein the total protein is about 200 pg per dose.40. The spray freeze-dried pharmaceutical composition of any one of paragraphs 26 to 39, wherein the multivalent vaccine has at least about 2%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, or at least about 50% less protein aggregation or degradation compared with a multivalent vaccine with the same composition that is formulated at the same concentration in a liquid formulation.41. The spray freeze-dried pharmaceutical composition of paragraph 40, wherein the protein aggregation or degradation is measured by SEC-HPLC, SDS-PAGE or Western blot assay.42. The spray freeze-dried pharmaceutical composition of any one of paragraphs 26 to 39, wherein the multivalent vaccine has similar immunogenic activity compared with a multivalent vaccine with the same components that is formulated at the same concentration in a liquid formulation.43. The spray freeze-dried pharmaceutical composition of paragraph 42, wherein the immunogenic activity is measured by the levels of antibody titers production in a subject inducedby administering to the subject the multivalent vaccine in a spray freeze-dried or liquid formulation.44. The spray freeze-dried pharmaceutical composition of any one of paragraphs 26 to 43, wherein the increase in the amount of aggregated or degraded protein in the composition is less than 15%, 10%, 5%, or 2% after storage at -20°C for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.45. The spray freeze-dried pharmaceutical composition of any one of paragraphs 26 to 43, wherein the increase in the amount of aggregated or degraded protein in the composition is less than 15%, 10%, 5%, or 2% after storage at 30°C for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.46. The spray freeze-dried pharmaceutical composition of any one of paragraphs 26 to 43, wherein the multivalent vaccine retains at least 70%, 80%, 90% or 95% of its initial immunogenic activity after storage at -20°C for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.47. The spray freeze-dried pharmaceutical composition of any one of paragraphs 26 to 43, wherein the multivalent vaccine retains at least 70% , 80%, 90% or 95% of its initial immunogenic activity after storage at 30°C for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.48. A method of generating the spray freeze-dried pharmaceutical composition of any one of paragraphs 26 to 47, comprising: a. dissolving the multicomponent vaccine, histidine-borate, phosphate buffer, sucrose, and polysorbate 80 in a suitable solvent to form a liquid composition; b. atomizing the liquid formulation into specifically sized spherical droplets; c. immediately freezing the droplets and locking in the size and shape of each individual particle; d. collecting the particles and drying the particles in bulk in a lyophilization chamber.49. A reconstituted pharmaceutical composition of any one of paragraphs 1 to 22, or 26 to 47 comprising: a. a multicomponent vaccine, b. a buffer, c. sucrose, d. polysorbate 80, and e. a reconstitution liquid wherein the multicomponent vaccine comprises: EHaH35LH48L, LukSmut9, LukFmuti, TBA225 and LukABmutso.50. The reconstituted pharmaceutical composition of paragraph 49, wherein the composition further comprises histidine-borate.51. The reconstituted pharmaceutical composition of paragraph 49 or 50, wherein the buffer is phosphate buffer.52. The reconstituted pharmaceutical composition of any one of paragraphs 49 to 51, wherein a. Hlau35LH48L comprises a Hla toxoid with H35L and H48L mutations, or comprises the amino acid sequence of SEQ ID NO: 1; b. LukSmut9 comprises the S subunit of a PVL toxoid with T28F, K97A, and S209A mutations, or comprises the amino acid sequence of SEQ ID NO: 2; c. LukFmuti comprises the F subunit of a PVL toxoid with K102A mutation, or comprises the amino acid sequence of SEQ ID NO: 3; d. LukABmutso comprises a dimeric toxoid form of LukAB with D39A mutation in LukA and R23E mutation in LukB, or comprises a first polypeptide comprising theamino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5; e. TBA225 comprises a fusion protein comprising: i. a TSST-1 toxoid with L30R, D27A, and 146 A mutations, ii. a SEB toxoid with L45R, Y89A, and Y94A mutations, and iii. a SEA toxoid with L48R, D70R, Y92A, and H225A mutations; or comprising the amino acid sequence of SEQ ID NO: 6.53. The reconstituted pharmaceutical composition of paragraph 52, wherein a. Hlau35LH48L consists of the amino acid sequence of SEQ ID NO: 1; b. LukSmut9 consists of the amino acid sequence of SEQ ID NO: 2; c. LukFmuti consists of the amino acid sequence of SEQ ID NO: 3; d. LukABmutso comprises a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5; and e. TBA225 consists of the amino acid sequence of SEQ ID NO: 6.54. The reconstituted pharmaceutical composition of any one of paragraphs 49 to 53, wherein the concentration of the total protein of the vaccine is about from 0.005 mg / ml to 10 mg / ml.55. The reconstituted pharmaceutical composition of any one of paragraphs 49 to 54, wherein the concentration of each component of the vaccine is about from 0.001 mg / ml to 2 mg / ml.56. The reconstituted pharmaceutical composition of any one of paragraphs 49 to 55, wherein the concentration of sucrose is about from 2% (weight / volume, 20 g / L) to 10% (weight / volume, 100 g / L).57. The reconstituted pharmaceutical composition of any one of paragraphs 49 to 56, wherein the concentration of polysorbate 80 is about from 0.004% (weight / volume, 0.04 g / L) to 2% (weight / volume, 20 g / L).58. The reconstituted pharmaceutical composition of any one of paragraphs 50 to 55, wherein the concentration of histidine-borate is about from O.lmM to 25mM.59. The reconstituted pharmaceutical composition of any one of paragraphs 51 to 58, wherein the concentration of phosphate buffer is about from 0.5mM to 20mM.60. The reconstituted pharmaceutical composition of any one of paragraphs 49 to 59, wherein the reconstituted pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at the ratio of 2: 400: 1 in weight.61. The reconstituted pharmaceutical composition of any one of paragraphs 51 to 60, wherein the concentration of the total protein is about 0.4 mg / ml (0.2 mg per dose), the concentration of the histidine-borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of the polysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5.62. The reconstituted pharmaceutical composition of any one of paragraphs 51 to 61, wherein the total protein is about 200 pg per dose .63. A method of treating or preventing Staphylococcus aureus (SA) infection in a subject, comprising administering to the subject the reconstituted pharmaceutical composition of any one of paragraphs 49 to 62.64. The method of paragraph 62, wherein the subject is a human subject.65. A composition suitable for lyophilization or spray -freeze drying, comprising: a. a multicomponent vaccine, b. a buffer, c. sucrose, and d. polysorbate 80, wherein the multicomponent vaccine comprises: HlaH35LH48L, LukSmut9, LukFmuti, TBA225 and LukABmutso.66. The composition of paragraph 65, wherein the composition further comprises histidine-borate.67. The composition of paragraph 26 or 66, wherein the buffer is phosphate buffer.68. The composition of any one of paragraphs 65 to 67, wherein the composition comprises the total protein, sucrose, and polysorbate 80 at the ratio of 2: 400: 1 in weight.69. The composition of paragraph 68, wherein the concentration of the total protein is about 0.4 mg / ml (0.2 mg per dose), the concentration of the histidine-borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of the polysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5.70. The composition of paragraph 67, wherein the total protein is about 200 pg per dose.71. A kit comprising one or more containers and instructions for use, wherein the one or more containers comprise the pharmaceutical composition of any one of paragraphs 1 to 22, 26 to 47.3.2 CONVENTIONS AND ABBREVIATIONS4. BRIEF DESCRIPTION OF THE DRAWINGS

[0085] Figures 1A-1C. Biochemical characterization of LTB-SA7 components in Lyo, SFD and Liq vaccine formulations. (Fig. 1 A) SDS-PAGE and (Fig. IB) Western Blot analysis of Lyo (Lane 2), SFD (Lane 4), Liq without desorption (Lane 6), Liq with desorption (Lane 7) and freshly prepared Liq without alhydrogel (Lane 9). Samples were loaded at Ipg for SDS-PAGE and lOOng for all antibodies in Western Blot, except anti-LukABmut50 which was loaded at 250ng. (Fig. 1C) SEC-HPLC of Liq (Top), Lyo (Middle) and SFD (Bottom).

[0086] Figures 2A-2E. Comparative immunogenicity and efficacy in a murine intradermal infection model. Mice (n=10 mice per group) were immunized with 50 pg of either Liq, Lyo, or SFD formulations of LTB-SA7 or 50 pg of BSA in 200pg of Alhydrogel (Al(0H)3) on days 0,14 and 28. On day 38, sera were collected to assess toxin neutralizing antibody titers in cellbased assays. On day 42, MRSA (8x 106 CFU of the bioluminescent MRSA strain SF8300) skin infections were performed on immunized mice and bacterial burden and lesion size monitored until the experiment was arbitrarily ended after 10 days. (Fig. 2A) Toxin neutralizing antibody titers. (Fig. 2B) Representative photographs of skin lesion. (Fig. 2C) Mean total lesion size (cm2) ± SEM. (Fig. 2D) Representative in vivo BLI (photons / s) (loglO scale). (Fig. 2E) Mean total flux (photons / s) ± SEM. *P < 0.05, fP < 0.01, JP < 0.001, as calculated by a two-way analysis of variance (ANOVA) Dunnett’s multiple comparisons test (Fig. 2C) and (Fig. 2E). Results are combined from two independent experiments.

[0087] Figures 3A-3F. Comparative immunogenicity and efficacy in rabbit pyomyositis.Rabbits (n=6 rabbits per group) were immunized with 50 pg of either Liq or Lyo formulations of LTB-SA7 or 50 pg of BSA in 200pg of Alhydrogel (Al(0H)3) on days 0, 14 and 28. On day 38, sera were collected to assess toxin binding IgG titers by Luminex, and toxin neutralizing antibody titers in cell-based assays. On day 42, MRSA (6-8 x l09 CFU of the bioluminescent MRSA strain SF8300) pyomyositis infections were performed on immunized rabbits and skin lesions and thigh width monitored until the experiment was arbitrarily ended after 7 days, when abscesses were imaged, weighted, and harvested for ex vivo CFUs. (Fig. 3A) Toxin-binding IgG titers. (Fig. 3B) Toxin neutralizing antibody titers. (Fig. 3C) Representative photographs of skin lesion and abscess. (Fig. 3D) Mean thigh width change (% of contralateral thigh) ± SEM. (Fig. 3E) Mean tissue weight of abscess ± SEM. (Fig. 3F) Geometric mean of ex vivo CFUs ± SD. *P < 0.05, fP < 0.01, fP < 0.001, as calculated by a two-way analysis of variance (ANOVA) Dunnett’s multiple comparisons test (Fig. 3D) or Kruskal -Wallis Dunn’s multiple comparisons test (Fig. 3E) and (Fig. 3F). Results are combined from two independent experiments.

[0088] Figures 4A-4C. Characterization of LMIC isolates in vitro. (Fig. 4A) LMIC isolates characterization workflow. (Fig. 4B) PCR based toxin profiling. (Fig. 4C) Toxin release profile of the LMIC isolates used for in vivo study.

[0089] Figures 5A-5C. Protective efficacy of LTB-SA7 against LMIC isolates in a mouse bacteremia model. Mice (n=10 mice per group) were immunized with 50 pg of either Liq or Lyo formulations of LTB-SA7 or 50 pg of BSA in 200pg of Alhydrogel (Al(0H)3) on days 0, 14 and 28. On day 42, the LMIC bacteremia infection was performed on immunized mice. (Fig. 5A) Survival (%) of mice infected with 8x107 CFU of KCO075. (Fig. 5B) Survival (%) of miceinfected with 4x107 CFU of Pyo603. (Fig. 5C) Survival (%) of mice infected with 2x107 CFU of Gaza209. *P < 0.05, fP < 0.01, fP < 0.001, BSA versus Liq or Lyo as calculated by log rank (Mantel-Cox) test. Results are from one independent experiment.

[0090] Figures 6A-6L. Protective efficacy of LTB-SA7 against LMIC isolates in a mouse intradermal infection model. Mice (n=10 mice per group) were immunized with 50 pg of either Liq or Lyo formulations of LTB-SA7 or 50 pg of BSA in 200pg of Alhydrogel (Al(0H)3) on days 0, 14 and 28. On day 42, intradermal infections with KCO075 (A-D), Pyo603 (E-H), and Gaza209 (LL) were performed on immunized mice and skin lesions monitored until the experiment was arbitrarily ended after 10 days, when skin and kidney were harvested for ex vivo CFUs. (Fig. 6A), (Fig. 6E), and (Fig. 61) Representative photographs of skin lesion. (Fig. 6B), (Fig. 6F), and (Fig. 6J) Mean total lesion size (cm2) ± SEM. (Fig. 6C), (Fig. 6G), and (Fig. 6K) Geometric mean of skin lesion ex vivo CFUs ± SD. (Fig. 6D), (Fig. 6H), and (Fig. 6L) Geometric mean of kidney ex vivo CFUs ± SD. *P < 0.05, fP < 0.01, fP < 0.001, as calculated by a two-way analysis of variance (ANOVA) Dunnett’s multiple comparisons test (Fig. 6B, Fig. 6F, Fig. 6G) or Kruskal -Wallis Dunn’s multiple comparisons test (Fig. 6C, Fig. 6D, Fig. 6G, Fig. 6H, Fig. 6K, Fig. 6L). Results are combined from two independent experiments, n.s., not significant.

[0091] Figures 7A-7D. Biochemical characterization of LTB-SA7 formulations after storage for 1 and 3 months. (Figs. 7A and 7C) SDS-PAGE analysis of Ipg Lyo LTB-SA7 stored at - 20°C (Lane 2) and 30°C (Lane 3), Ipg SFD LTB-SA7 stored at -20°C (Lane 5) and 30°C (Lane 6), Ipg Liq LTB-SA7 stored at 30°C without desorption (Lane 8) and with desorption (Lane 9) and Ipg freshly prepared Liq LTB-SA7 without alhydrogel without desorption (Lane 11) and with desorption (Lane 12) after storage for 1 month (Fig. 7A) and 3 months (Fig. 7C). (Fig. 7B and Fig. 7D) SEC-HPLC of Lyo (-20°C, 30°C), SFD (-20°C, 30°C), Liq (30°C, ± desorption) and freshly prepared liq (± desorption) after storage for 1 month (Fig. 7B) and 3 months (Fig. 7D).

[0092] Figures 8A-8F. Biochemical characterization of the Lyo LTB-SA7 formulation after storage for 6, 9, and 12 months. (Fig. 8A, Fig. 8C, Fig. 8E) SDS-PAGE analysis of Ipg Lyo LTB-SA7 stored at -20°C (Lane 2) and 30°C (Lane 3) and Ipg freshly prepared Liq LTB-SA7 without alhydrogel (6mo: Lanes 5, 9; 12 mo: Lane 4) after storage for 6 months (Fig. 8A), 9 months (Fig. 8C), and 12 months (Fig. 8E). (Fig. 8B, Fig. 8D, Fig. 8F) SEC-HPLC of Lyo LTB-SA7 stored at -20°C and 30°C and freshly prepared Liq without alhydrogel after storage for 6 months (Fig. 8B), 9 months (Fig. 8D), and 12 months (Fig. 8F).

[0093] Figure 9. Immunogenicity of the Lyo LTB-SA7 formulation after long-term storage. Serum toxin neutralizing titers to toxins Hla, PVL, LukAB, SEA, SEB, TSST-1 for individual BALB / c mice (n = 5 / group) immunized with 40pg of Lyo LTB-SA7 on Day 0 of stability study or after 6 months storage of vaccine at either -20°C or 30°C. Bars indicate mean log-transformed ND50, the serum dilution that elicits 50% of neutralizing titer. Dotted lines indicate the limit of detection for each toxin (LOD). Statistical analysis performed with the Mann-Whitney test.

[0094] Figures 10A-10B. Toxin neutralization of LMIC supernatants in vitro. Toxicity of bacterial supernatants and neutralizing efficacy of LTB-SA7 pAbs tested with rabbit red blood cells (Fig. 10A) and induced HL-60 cells (Fig. 10B). Effective dilutions of bacterial supernatants causing 85% toxicity (ED85) against RRBCs, and HL-60 cells were calculated for each LMIC isolate. Bacterial SUP dilutions [1 : 17.3 (KCO075); 1 : 171 (pyo603); 1 :32.3 (Gaza209)] resulting in ED85 were used to determine concentration of LTB-SA7 Rb pAb required to neutralize 50% of bacterial SUP toxicity (NC50).5. DETAILED DESCRIPTION OF THE INVENTION

[0095] Provided herein are pharmaceutical compositions and their use in preventing and treating infections with Staphylococcus aureus (SA). In some embodiments, compositions provided in Section 5.1 are formulated such that they have one or more functional properties described in Section 5.2. In certain embodiments, the pharmaceutical compositions provided herein has various advantages, for example, improved long-term stability under various conditions. Also provided herein are methods of preparing the compositions provided in Section 5.1 (section 5.3). Also provided herein are assays that may be used in related studies (Section 5.6).5.1 FORMULATIONS OF PHARMACEUTICAL COMPOSITION5.1.1 LYOPHILIZED FORMULATION OF PHARMACEUTICAL COMPOSITION

[0096] The disclosure provides a lyophilized pharmaceutical composition comprising a multicomponent vaccine (e.g. such as described in Section 5.4 below), a buffer, a stabilizer, and a surfactant. In some embodiments, the lyophilized pharmaceutical composition furthercomprises histidine-borate. In some embodiments, the lyophilized pharmaceutical composition comprises a multicomponent vaccine, histidine-borate, a buffer, a stabilizer, and a surfactant.

[0097] In some embodiment, the buffer is phosphate buffer. In some embodiment, the buffer is tris buffer.

[0098] In some embodiments, the stabilizer comprises sucrose.

[0099] In some embodiments, the surfactant comprises polysorbate 80. In some embodiments, the surfactant comprises polysorbate 20.

[0100] In one aspect, the disclosure provides a lyophilized pharmaceutical composition comprising a multicomponent vaccine, phosphate buffer, sucrose, and polysorbate 80.

[0101] In one aspect, the disclosure provides a lyophilized pharmaceutical composition comprising a multicomponent vaccine, histidine-borate, phosphate buffer, sucrose, and polysorbate 80.

[0102] In one aspect, the disclosure provides a lyophilized pharmaceutical composition comprising a multicomponent vaccine, tris buffer, sucrose, and polysorbate 80.

[0103] In one aspect, the disclosure provides a lyophilized pharmaceutical composition comprising a multicomponent vaccine, histidine-borate, tris buffer, sucrose, and polysorbate 80.

[0104] In some embodiments, the multicomponent vaccine comprises: EHaH35LH48L, LukSmut9, LukFmuti, TBA225 and LukABmutso.

[0105] In some embodiments, EHaH35LH48L comprises a Hla toxoid with H35L and H48L mutations. In some embodiments, EHaH35LH48L comprises the amino acid sequence of SEQ ID NO: 1. In some embodiments, EHaH35LH48L consists of the amino acid sequence of SEQ ID NO: 1.

[0106] In some embodiments, LukSmut9 comprises the S subunit of a PVL toxoid with T28F, K97A, and S209A mutations. In some embodiments, LukSmut9 comprises comprises the amino acid sequence of SEQ ID NO: 2. In some embodiments, LukSmut9 consists of the amino acid sequence of SEQ ID NO: 2.

[0107] In some embodiments, LukFmuti comprises the F subunit of a PVL toxoid with K102A mutation. In some embodiments, LukFmuti comprises the amino acid sequence of SEQ ID NO: 3. In some embodiments, LukFmuti consists of the amino acid sequence of SEQ ID NO: 3.

[0108] In some embodiments, LukABmutso comprises a dimeric toxoid form of LukAB with D39A mutation in LukA and R23E mutation in LukB. In some embodiments, LukABmutsocomprises a variant of LukA comprising D39A mutation in LukA and a variant of LukB comprising R23E mutation in LukB. In some embodiments, LukABmutso comprises a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO:5. In some embodiments, LukABmutso comprises a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO:5.

[0109] In some embodiments, TBA225 comprises a fusion protein comprising: (1) a TSST-1 toxoid with L30R, D27A, and I46A mutations, (2) a SEB toxoid with L45R, Y89A, and Y94A mutations, and (3) a SEA toxoid with L48R, D70R, Y92A, and H225A mutations. In some embodiments, the three toxoids are fused together via a linker. In some embodiemnts, the linker comprise the amino acid sequence of GGGSGGGSGGGS (SEQ ID NO: 7). In some embodiments, TBA225 comprises the amino acid sequence of SEQ ID NO: 6. In some embodiments, TBA225 consists of the amino acid sequence of SEQ ID NO: 6.

[0110] In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about from 0.005 mg / ml to 10 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is from 0.005 mg / ml to 10 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about from 0.01 mg / ml to 10 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is from 0.01 mg / ml to 10 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about from 0.05 mg / ml to 5 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is from 0.05 mg / ml to 5 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about from 0.1 mg / ml to 1 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is from 0.1 mg / ml to 1mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about from 0.2 mg / ml to 0.5 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is from 0.2 mg / ml to 0.5 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about from 0.4 mg / ml to 0.5 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is from 0.4 mg / ml to 0.5 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is at least 0.005 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is at least 0.01 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is at least 0.025 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is at least 0.05 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is at least 0.1 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is at most 10 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is at most 7.5 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is at most 5 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is at most 2.5 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccineis at most 1 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about 1 mg / ml, 0.9 mg / ml, 0.8 mg / ml, 0.7 mg / ml, 0.6 mg / ml, 0.5 mg / ml, 0.4 mg / ml, 0.3 mg / ml, 0.2 mg / ml, 0.1 mg / ml, 0.09 mg / ml, 0.08 mg / ml, 0.075 mg / ml, 0.07 mg / ml, 0.06 mg / ml, 0.05 mg / ml, 0.04 mg / ml, 0.03 mg / ml, 0.025 mg / ml, 0.02 mg / ml, 0.01 mg / ml, 0.009 mg / ml, 0.008 mg / ml, 0.007 mg / ml, 0.00625 mg / ml, or 0.005 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is of 1 mg / ml, 0.9 mg / ml, 0.8 mg / ml, 0.7 mg / ml, 0.6 mg / ml, 0.5 mg / ml, 0.4 mg / ml, 0.3 mg / ml, 0.2 mg / ml, 0.1 mg / ml, 0.09 mg / ml, 0.08 mg / ml, 0.075 mg / ml, 0.07 mg / ml, 0.06 mg / ml, 0.05 mg / ml, 0.04 mg / ml, 0.03 mg / ml, 0.025 mg / ml, 0.02 mg / ml, 0.01 mg / ml, 0.009 mg / ml, 0.008 mg / ml, 0.007 mg / ml, 0.00625 mg / ml, or 0.005 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about 0.4 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is 0.4 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about 0.3 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is 0.3 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about 0.2 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is 0.2 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about 0.1 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is 0.1 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about 0.075 mg / ml upon reconstitution in a liquidformulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is 0.075 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about 0.05 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is 0.05 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about 0.025 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is 0.025 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about 0.01 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is 0.01 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about 0.00625 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is 0.00625 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about 0.005 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is 0.005 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 500 pg per dose, 450 pg per dose, 400 pg per dose, 350 pg per dose, 300 pg per dose, 250 pg per dose, 200 pg per dose, 150 pg per dose, 100 pg per dose, 50 pg per dose, 45 pg per dose, 40 pg per dose, 37.5 pg per dose, 35 pg per dose, 30 pg per dose, 25 pg per dose, 20 pg per dose, 15 pg per dose, 12.5 pg per dose, 10 pg per dose, 5 pg per dose, 4.5 pg per dose, 4 pg per dose, 3.5 pg per dose, 3.125 pg per dose, or 2.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 500 pg per dose,450 pg per dose, 400 pg per dose, 350 pg per dose, 300 pg per dose, 250 pg per dose, 200 pg per dose, 150 pg per dose, 100 pg per dose, 50 pg per dose, 45 pg per dose, 40 pg per dose, 37.5 pg per dose, 35 pg per dose, 30 pg per dose, 25 pg per dose, 20 pg per dose, 15 pg per dose, 12.5 pg per dose, 10 pg per dose, 5 pg per dose, 4.5 pg per dose, 4 pg per dose, 3.5 pg per dose, 3.125 pg per dose, or 2.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 200 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 200 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 175 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 175 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 150 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 150 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 100 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 100 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 75 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 75 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 50 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 50 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 25 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 25 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 12.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 12.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 10 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein ofthe vaccine is 10 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 3.125 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 3.125 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 2.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 2.5 pg per dose.

[0111] In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is about the same. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is the same. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is about from 0.001 mg / ml to 2 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is from 0.001 mg / ml to 2 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is about from 0.002 mg / ml to 2 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is from 0.002 mg / ml to 2 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is about from 0.01 mg / ml to 1 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is from 0.01 mg / ml to 1 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is about from 0.02 mg / ml to 0.2 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccineis from 0.02 mg / ml to 0.2 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is about from 0.04 mg / ml to 0.1 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is from 0.04 mg / ml to 0.1 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is about from 0.08 mg / ml to 0.1 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is from 0.08 mg / ml to 0.1 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is at least 0.001 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is at least 0.002 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is at least 0.005 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is at least 0.01 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is at least 0.02 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is at most 2 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is at most 1.5 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is at most 1 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is at most 0.5 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, theconcentration of each component of the vaccine is at most 0.2 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is about 0.2 mg / ml, 0.18 mg / ml, 0.16 mg / ml, 0.14 mg / ml, 0.12 mg / ml, 0.1 mg / ml, 0.08 mg / ml, 0.06 mg / ml, 0.04 mg / ml, 0.02 mg / ml, 0.018 mg / ml, 0.016 mg / ml, 0.025 mg / ml, 0.014 mg / ml, 0.012 mg / ml, 0.01 mg / ml, 0.008 mg / ml, 0.006 mg / ml, 0.005 mg / ml, 0.004 mg / ml, 0.002 mg / ml, 0.0018 mg / ml, 0.0016 mg / ml, 0.0014 mg / ml, 0.00125 mg / ml, or 0.001 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is 0.2 mg / ml, 0.18 mg / ml, 0.16 mg / ml, 0.14 mg / ml, 0.12 mg / ml, 0.1 mg / ml, 0.08 mg / ml, 0.06 mg / ml, 0.04 mg / ml, 0.02 mg / ml, 0.018 mg / ml, 0.016 mg / ml, 0.025 mg / ml, 0.014 mg / ml, 0.012 mg / ml, 0.01 mg / ml, 0.008 mg / ml, 0.006 mg / ml, 0.005 mg / ml, 0.004 mg / ml, 0.002 mg / ml, 0.0018 mg / ml, 0.0016 mg / ml, 0.0014 mg / ml, 0.00125 mg / ml, or 0.001 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is about 0.08 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein the concentration of each component of the vaccine is 0.08 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is about 0.06 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein the concentration of each component of the vaccine is 0.06 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is about 0.04 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein the concentration of each component of the vaccine is 0.04 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, each competent of the vaccine is about 0.04 mg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each competent of the vaccine is 0.04 mg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is about 0.02 mg / ml upon reconstitution in a liquid formulation. In someembodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is 0.02 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is about 0.015 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is 0.015 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is about 0.01 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is 0.01 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is about 0.005 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is 0.005 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is about 0.002 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is 0.002 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is about 0.00125 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is 0.00125 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is about 0.001 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of each component of the vaccine is 0.001 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 100 pg per dose, 90 pg per dose, 80 pg per dose, 70 pg per dose, 60 pg per dose, 50 pg per dose, 40 pg per dose, 30 pg per dose, 20 pg per dose,10 pg per dose, 9 pg per dose, 8 pg per dose, 7.5 pg per dose, 5 pg per dose, 6 pg per dose, 5 pg per dose, 4 pg per dose, 3 pg per dose, 2.5 pg per dose, 2 pg per dose, 1 pg per dose, 0.9 pg per dose, 0.8 pg per dose, 0.7 pg per dose, 0.625 pg per dose, or 0.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 100 pg per dose, 90 pg per dose, 80 pg per dose, 70 pg per dose, 60 pg per dose, 50 pg per dose, 40 pg per dose, 30 pg per dose, 20 pg per dose, 10 pg per dose, 9 pg per dose, 8 pg per dose, 7.5 pg per dose, 5 pg per dose, 6 pg per dose, 5 pg per dose, 4 pg per dose, 3 pg per dose, 2.5 pg per dose, 2 pg per dose, 1 pg per dose, 0.9 pg per dose, 0.8 pg per dose, 0.7 pg per dose, 0.625 pg per dose, or 0.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 40 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 40 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 35 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 35 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 30 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 30 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 20 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 20 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 15 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 15 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 10 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 10 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 2.5 pg perdose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 2.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 2 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 2 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 1 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 1 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 0.625 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 0.625 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 0.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 0.5 pg per dose.

[0112] In some embodiments, the lyophilized pharmaceutical composition provided herein does not comprise histidine-borate. In some embodiments, the lyophilized pharmaceutical composition provided herein comprises histidine-borate. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of histidine-borate is about from 0. ImM to 50mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of histidine-borate is from O.lmM to 50mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of histidine-borate is about from O.lmM to 40mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of histidine- borate is from 0. ImM to 40mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of histidine-borate is about from O.lmM to 30mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of histidine-borate is from O.lmM to 30mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of histidine-borate is about from 5mM to 25 mM upon reconstitution ina liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of histidine-borate is from 5mM to 25 mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of histidine-borate is about from lOmM to 25mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of histidine-borate is from lOmM to 25mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of histidine-borate is about from 15mM to 25mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of histidine-borate is from 15mM to 25mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of histidine-borate is at least O.lmM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of histidine-borate is at least 0.5mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of histidine-borate is at least ImM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of histidine-borate is at least 5mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of histidine-borate is at most 50mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of histidine-borate is at most 40mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of histidine-borate is at most 35mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of histidine-borate is about 15mM, 16 mM, 17 mM, 18 mM, 19 mM, 20 mM, 21 mM, 22 mM, 23 mM, 24 mM, 25 mM, 26 mM, 27 mM, 28 mM, 29 mM, 30 mM, 31 mM, 32 mM, 33 mM, 34 mM, or 35 mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of histidine-borate is ofl5mM, 16 mM, 17 mM, 18 mM, 19 mM, 20 mM, 21 mM, 22 mM, 23 mM, 24 mM, 25 mM, 26 mM, 27mM, 28 mM, 29 mM, 30 mM, 31 mM, 32 mM, 33 mM, 34 mM, or 35 mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of histidine-borate is about 25mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of histidine-borate is 25mM upon reconstitution in a liquid formulation.

[0113] In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the buffer is about from O.lmM to 30mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the buffer is from 0. ImM to 30mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the buffer is about from 0.2mM to 20mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the buffer is from 0.2mM to 20mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the buffer is about from 0.5mM to 20mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the buffer is from 0.5mM to 20mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the buffer is about from 0.5mM to lOmM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the buffer is from 0.5mM to lOmM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the buffer is about from ImM to 5mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the buffer is from ImM to 5mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the buffer is about from ImM to 3mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the buffer is from ImM to 3mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilizedpharmaceutical composition provided herein, the concentration of the buffer is at least 0. ImM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the buffer is at least 0.2mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the buffer is at least 0.5mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the buffer is at least 0.75mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the buffer is at least ImM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the buffer is at most 30mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the buffer is at most 20mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the buffer is at most lOmM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the buffer is at most 5mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the buffer is at most 3mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the buffer is about 0.5 mM, 0.6 mM, 0.7 mM, 0.8 mM, 0.9 mM, 1 mM, 1.1 mM, 1.2 mM, 1.3 mM, 1.4 mM, 1.5 mM, 1.6 mM, 1.7 mM, 1.8 mM, 1.9 mM, 2.0 mM, 2.1 mM, 2.2 mM, 2.3 mM, 2.4 mM, 2.5 mM, 2.6 mM, 2.7 mM, 2.8 mM, 2.9 mM, or 3mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the buffer is of 0.5 mM, 0.6 mM, 0.7 mM, 0.8 mM, 0.9 mM, 1 mM, 1.1 mM, 1.2 mM, 1.3 mM, 1.4 mM, 1.5 mM, 1.6 mM, 1.7 mM, 1.8 mM, 1.9 mM, 2.0 mM, 2.1 mM, 2.2 mM, 2.3 mM, 2.4 mM, 2.5 mM, 2.6 mM, 2.7 mM, 2.8 mM, 2.9 mM, or 3mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the buffer is about 2mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, theconcentration of the buffer is 2mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the buffer is about 1 ,2mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the buffer is 1.2mM upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the buffer is phosphate buffer. In some embodiments of the lyophilized pharmaceutical composition provided herein, the buffer is tris buffer.

[0114] In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the stabilizer is about from 1% (weight / volume, 10 g / L) to 30% (weight / volume, 300 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the stabilizer is from 1% (weight / volume, 10 g / L) to 30% (weight / volume, 300 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the stabilizer is about from 2% (weight / volume, 20 g / L) to 20% (weight / volume, 200 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the stabilizer is from 2% (weight / volume, 20 g / L) to 20% (weight / volume, 200 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the stabilizer is about from 2% (weight / volume, 20 g / L) to 15% (weight / volume, 150 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the stabilizer is from 2% (weight / volume, 20 g / L) to 15% (weight / volume, 150 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the stabilizer is about from 2% (weight / volume, 20 g / L) to 10% (weight / volume, 100 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the stabilizer is from 2% (weight / volume, 20 g / L) to 10% (weight / volume, 100 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the stabilizer is about from 5% (weight / volume, 50 g / L) to 10% (weight / volume, 100 g / L) upon reconstitution ina liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the stabilizer is from 5% (weight / volume, 50 g / L) to 10% (weight / volume, 100 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the stabilizer is at least 1% (weight / volume, 10 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the stabilizer is at least 2% (weight / volume, 20 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the stabilizer is at least 3% (weight / volume, 30 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the stabilizer is at least 4% (weight / volume, 40 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the stabilizer is at least 5% (weight / volume, 50 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the stabilizer is at most 30% (weight / volume, 300 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the stabilizer is at most 25% (weight / volume, 250 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the stabilizer is at most 20% (weight / volume, 200 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the stabilizer is at most 15% (weight / volume, 150 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the stabilizer is about 1% (weight / volume, 10 g / L), 2% (weight / volume, 20 g / L), 3%(weight / volume, 30 g / L), 4%(weight / volume, 40 g / L), 5%(weight / volume, 50 g / L), 6%(weight / volume, 60 g / L), 7%(weight / volume, 70 g / L), 8%(weight / volume, 80 g / L), 9%(weight / volume, 90 g / L), 10%(weight / volume, 100 g / L), 1 l%(weight / volume, 110 g / L), 12%(weight / volume, 120 g / L), 13%(weight / volume, 130 g / L), 14%(weight / volume, 140 g / L), 15%(weight / volume, 150 g / L), 16%(weight / volume, 160 g / L), 17%(weight / volume, 170 g / L), 18%(weight / volume, 180 g / L), 19%(weight / volume, 190 g / L), or 20% (weight / volume, 200 g / L) upon reconstitution in a liquidformulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the stabilizer is of 1% (weight / volume, 10 g / L), 2% (weight / volume, 20 g / L), 3%(weight / volume, 30 g / L), 4%(weight / volume, 40 g / L), 5%(weight / volume, 50 g / L), 6%(weight / volume, 60 g / L), 7%(weight / volume, 70 g / L), 8%(weight / volume, 80 g / L), 9%(weight / volume, 90 g / L), 10%(weight / volume, 100 g / L), 1 l%(weight / volume, 110 g / L), 12%(weight / volume, 120 g / L), 13%(weight / volume, 130 g / L), 14%(weight / volume, 140 g / L), 15%(weight / volume, 150 g / L), 16%(weight / volume, 160 g / L), 17%(weight / volume, 170 g / L), 18%(weight / volume, 180 g / L), 19%(weight / volume, 190 g / L), or 20% (weight / volume, 200 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the stabilizer is about 8% (weight / volume, 80 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the stabilizer is 8% (weight / volume, 80 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the stabilizer is sucrose.

[0115] In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the surfactant is about from 0.004% (weight / volume, 0.04 g / L) to 2% (weight / volume, 20 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the surfactant is from 0.004% (weight / volume, 0.04 g / L) to 2% (weight / volume, 20 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the surfactant is about from 0.01% (weight / volume, 0.1 g / L) to 0.5% (weight / volume, 5 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the surfactant is from 0.01% (weight / volume, 0.1 g / L) to 0.5% (weight / volume, 5 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the surfactant is about from 0.01% (weight / volume, 0.1 g / L) to 0.1% (weight / volume, 1 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the surfactant is from 0.01% (weight / volume, 0.1 g / L) to 0.1% (weight / volume, 1 g / L) upon reconstitution in a liquid formulation. . In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the surfactant isabout from 0.01% (weight / volume, 0.1 g / L) to 0.05% (weight / volume, 0.5 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the surfactant is from 0.01% (weight / volume, 0.1 g / L) to 0.05% (weight / volume, 0.5 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the surfactant is at least 0.004% (weight / volume, 0.04 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the surfactant is at least 0.006% (weight / volume, 0.06 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the surfactant is at least 0.008% (weight / volume, 0.08 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the surfactant is at least 0.01% (weight / volume, 0.1 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the surfactant is at most 2% (weight / volume, 20 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the surfactant is at most 1.5% (weight / volume, 15 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the surfactant is at most 1% (weight / volume, 10 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the surfactant is about 0.005% (weight / volume, 0.05 g / L), 0.01% (weight / volume, 0.1 g / L), 0.015% (weight / volume, 0.15 g / L), 0.02% (weight / volume, 0.2 g / L), 0.03% (weight / volume, 0.3 g / L), 0.04% (weight / volume, 0.4 g / L), 0.05% (weight / volume, 0.5 g / L), 0.06% (weight / volume, 0.6 g / L), 0.07% (weight / volume, 0.7 g / L), 0.08% (weight / volume, 0.8 g / L), 0.09% (weight / volume, 0.9 g / L), or 0.1% (weight / volume, 1.0 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the surfactant is of 0.005% (weight / volume, 0.05 g / L), 0.01% (weight / volume, 0.1 g / L), 0.015% (weight / volume, 0.15 g / L), 0.02% (weight / volume, 0.2 g / L), 0.03% (weight / volume, 0.3 g / L), 0.04% (weight / volume, 0.4 g / L), 0.05% (weight / volume, 0.5 g / L), 0.06% (weight / volume, 0.6 g / L), 0.07% (weight / volume, 0.7 g / L), 0.08% (weight / volume, 0.8 g / L), 0.09% (weight / volume,0.9 g / L), or 0.1% (weight / volume, 1.0 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the surfactant is about 0.02% (weight / volume, 0.2 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the concentration of the surfactant is 0.02% (weight / volume, 0.2 g / L) upon reconstitution in a liquid formulation. In some embodiments of the lyophilized pharmaceutical composition provided herein, the surfactant is polysorbate 20 or polysorbate 80. In some embodiments of the lyophilized pharmaceutical composition provided herein, the surfactant is polysorbate 80.

[0116] In certain embodiments, the pH of the lyophilized pharmaceutical composition is about from 6.0 to 9.0 upon reconstitution in a liquid formulation. In certain embodiments, the pH of the lyophilized pharmaceutical composition is about 6, 6.5, 7, 7.5, 8, 8.5 or 9 upon reconstitution in a liquid formulation. In some embodiments, the pH of the lyophilized pharmaceutical composition is about 7.5 upon reconstitution in a liquid formulation. In certain embodiments, the pH of the lyophilized pharmaceutical composition is from 6.0 to 9.0 upon reconstitution in a liquid formulation. In certain embodiments, the pH of the lyophilized pharmaceutical composition is 6, 6.5, 7, 7.5, 8, 8.5 or 9 upon reconstitution in a liquid formulation. In certain embodiments, the pH of the lyophilized pharmaceutical composition is 7.5 upon reconstitution in a liquid formulation.

[0117] In some embodiments of the lyophilized pharmaceutical composition provided herein, the lyophilized pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 2: 400: 1 by weight. In some embodiments of the lyophilized pharmaceutical composition provided herein, the lyophilized pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 1.5: 400: 1 by weight. In some embodiments of the lyophilized pharmaceutical composition provided herein, the lyophilized pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 1 : 400: 1 by weight. In some embodiments of the lyophilized pharmaceutical composition provided herein, the lyophilized pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 0.75: 400: 1 by weight. In some embodiments of the lyophilized pharmaceutical composition provided herein, the lyophilized pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 0.5: 400: 1 by weight. In some embodiments of the lyophilized pharmaceuticalcomposition provided herein, the lyophilized pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 0.25: 400: 1 by weight. In some embodiments of the lyophilized pharmaceutical composition provided herein, the lyophilized pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 0.125: 400: 1 by weight. In some embodiments of the lyophilized pharmaceutical composition provided herein, the lyophilized pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 0.03125: 400: 1 by weight. In some embodiments of the lyophilized pharmaceutical composition provided herein, the lyophilized pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 0.025: 400: 1 by weight.

[0118] In some embodiments of the lyophilized pharmaceutical composition provided herein, the lyophilized pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at a ratio of 2: 400: 1 by weight. In some embodiments of the lyophilized pharmaceutical composition provided herein, the lyophilized pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at a ratio of 1.5: 400: 1 by weight. In some embodiments of the lyophilized pharmaceutical composition provided herein, the lyophilized pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at a ratio of 1 : 400: 1 by weight. In some embodiments of the lyophilized pharmaceutical composition provided herein, the lyophilized pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at a ratio of 0.75: 400: 1 by weight. In some embodiments of the lyophilized pharmaceutical composition provided herein, the lyophilized pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at a ratio of 0.5: 400: 1 by weight. In some embodiments of the lyophilized pharmaceutical composition provided herein, the lyophilized pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at a ratio of 0.25: 400: 1 by weight. In some embodiments of the lyophilized pharmaceutical composition provided herein, the lyophilized pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at a ratio of 0.125: 400: 1 by weight. In some embodiments of the lyophilized pharmaceutical composition provided herein, the lyophilized pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at a ratio of 0.03125: 400: 1 by weight. In some embodiments of the lyophilized pharmaceutical composition provided herein, the lyophilizedpharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at a ratio of 0.025: 400: 1 by weight.

[0119] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) tris buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmuti comprising the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.4mg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 0.2 mg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 0.04 mg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 0.2 mg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 0.04 mg per dose.

[0120] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) tris buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmuti consisting of the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.4mg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 0.2 mg per dose. In some embodimentsof the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 0.04 mg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 0.2 mg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 0.04 mg per dose.

[0121] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) tris buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmuti comprising the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.4mg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 0.2 mg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 0.04 mg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 0.2 mg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 0.04 mg per dose.

[0122] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) tris buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmuti consisting of the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.4mg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 0.2 mg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 0.04 mg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 0.2 mg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 0.04 mg per dose.

[0123] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) phosphate buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmuti comprising the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.4mg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 0.2 mg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 0.04 mg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 0.2 mg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 0.04 mg per dose.

[0124] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) phosphate buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmuti consistingof the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.4mg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 0.2 mg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 0.04 mg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 0.2 mg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 0.04 mg per dose.

[0125] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) phosphate buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: Hlau35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmuti comprising the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.4mg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 0.2 mg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 0.04 mg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 0.2 mg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 0.04 mg per dose.

[0126] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) phosphate buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L),and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: Hlau35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmuti consisting of the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.4mg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 0.2 mg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 0.04 mg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 0.2 mg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 0.04 mg per dose.

[0127] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) tris buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmuti comprising the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0. Img / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 50 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 10 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 50 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 10 pg per dose.

[0128] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) tris buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmuti consisting of the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of O.lmg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 50 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 10 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 50 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 10 pg per dose.

[0129] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) tris buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmuti comprising the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of O. lmg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 50 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 10 pg per dose. In some embodiments of the lyophilizedpharmaceutical composition provided herein, the total protein of the vaccine is 50 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 10 pg per dose.

[0130] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) tris buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmuti consisting of the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of O.lmg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 50 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 10 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 50 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 10 pg per dose.

[0131] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) phosphate buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmuti comprising the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0. Img / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the totalprotein of the vaccine is about 50 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 10 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 50 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 10 pg per dose.

[0132] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) phosphate buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmuti consisting of the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of O.lmg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 50 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 10 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 50 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 10 pg per dose.

[0133] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) phosphate buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmuti comprising the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5,TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of O.lmg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 50 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 10 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 50 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 10 pg per dose.

[0134] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) phosphate buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: Hlau35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmuti consisting of the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0. Img / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 50 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 10 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 50 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 10 pg per dose.

[0135] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) tris buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmuti comprising theamino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.025mg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 12.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 2.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 12.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 2.5 pg per dose.

[0136] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) tris buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: EHau35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmuti consisting of the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.025mg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 12.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 2.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 12.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 2.5 pg per dose.

[0137] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) tris buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5)polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmuti comprising the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.025mg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 12.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 2.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 12.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 2.5 pg per dose.

[0138] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) tris buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmuti consisting of the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.025mg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 12.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 2.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 12.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 2.5 pg per dose.

[0139] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) phosphate buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmuti comprising the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.025mg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 12.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 2.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 12.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 2.5 pg per dose.

[0140] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) phosphate buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmuti consisting of the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.025mg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 12.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 2.5 pg per dose. In some embodiments of the lyophilized pharmaceuticalcomposition provided herein, the total protein of the vaccine is 12.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 2.5 pg per dose.

[0141] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) phosphate buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmuti comprising the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.025mg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 12.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 2.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 12.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 2.5 pg per dose.

[0142] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) phosphate buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmuti consisting of the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.025mg / ml. In someembodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 12.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 2.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 12.5 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 2.5 pg per dose.

[0143] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) tris buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmuti comprising the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.00625mg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 3.125 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 0.625 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 3.125 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 0.625 pg per dose.

[0144] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) tris buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmuti consisting of the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting ofthe amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.00625mg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 3.125 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 0.625 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 3.125 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 0.625 pg per dose.

[0145] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) tris buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: EHau35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmuti comprising the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.00625mg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 3.125 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 0.625 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 3.125 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 0.625 pg per dose.

[0146] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) tris buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: EHau35LH48L consisting of theamino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmuti consisting of the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.00625mg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 3.125 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 0.625 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 3.125 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 0.625 pg per dose.

[0147] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) phosphate buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: EHau35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmuti comprising the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.00625mg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 3.125 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 0.625 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 3.125 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 0.625 pg per dose.

[0148] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) phosphate buffer at the concentration of 1.2mM, (3) sucrose at theconcentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmuti consisting of the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.00625mg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 3.125 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 0.625 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 3.125 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 0.625 pg per dose.

[0149] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) phosphate buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmuti comprising the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.00625mg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 3.125 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 0.625 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein ofthe vaccine is 3.125 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 0.625 pg per dose.

[0150] In some embodiments, the lyophilized pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) phosphate buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmuti consisting of the amino acid sequence of SEQ ID NO: 3, LukABmutso comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.00625mg / ml. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is about 3.125 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is about 0.625 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, the total protein of the vaccine is 3.125 pg per dose. In some embodiments of the lyophilized pharmaceutical composition provided herein, each component of the vaccine is 0.625 pg per dose.

[0151] In some embodiments, the lyophilized pharmaceutical composition comprises a residual moisture content between about 1% and about 7%. In some embodiments, the lyophilized pharmaceutical composition comprises a residual moisture content between about 2% and about 6%. In some embodiments, the lyophilized pharmaceutical composition comprises a residual moisture content between about 3% and about 5%. In some embodiments, the lyophilized pharmaceutical composition comprises a residual moisture content about 3%. In some embodiments, the lyophilized pharmaceutical composition comprises a residual moisture content about 4%. In some embodiments, the lyophilized pharmaceutical composition comprises a residual moisture content about 5%. In some embodiments, the lyophilized pharmaceutical composition comprises a residual moisture content between 1% and 7%. In some embodiments, the lyophilized pharmaceutical composition comprises a residual moisture content between 2% and 6%. In some embodiments, the lyophilized pharmaceutical composition comprises aresidual moisture content between 3% and 5%. In some embodiments, the lyophilized pharmaceutical composition comprises a 3% residual moisture content. In some embodiments, the lyophilized pharmaceutical composition comprises a 4% residual moisture content. In some embodiments, the lyophilized pharmaceutical composition comprises a 5% residual moisture content.

[0152] As used herein and unless otherwise specified, the term “about” means within plus or minus 10% of a given value or range.

[0153] In certain embodiments, the lyophilized pharmaceutical composition is contained within a vial. The vial can be as small as 0.2 mL or less, or as large as 100 mL. Exemplar vials may be made of clear glass or amber glass, type I borosilicate glass, type II soda-silicate glass, or type III soda-silicate glass. The vial may be closed with a stopper, cap, flip cap, or a screw cap. In certain embodiments, the lyophilized pharmaceutical composition is contained within a syringe.5.1.2 SPRAY FREEZE-DRIED FORMULATION OF PHARMACEUTICAL COMPOSITION

[0154] The disclosure provides a spray freeze-dried pharmaceutical composition comprising a multicomponent vaccine (e.g. such as described in Section 5.4 below), a buffer, a stabilizer, and a surfactant. In some embodiments, the spray freeze-dried pharmaceutical composition further comprises histidine-borate. In some embodiments, the spray freeze-dried pharmaceutical composition comprises a multicomponent vaccine, histidine-borate, a buffer, a stabilizer, and a surfactant.

[0155] In some embodiment, the buffer is phosphate buffer. In some embodiment, the buffer is tris buffer.

[0156] In some embodiments, the stabilizer comprises sucrose.

[0157] In some embodiments, the surfactant comprises polysorbate 80. In some embodiments, the surfactant comprises polysorbate 20.

[0158] In one aspect, the disclosure provides a spray freeze-dried pharmaceutical composition comprising a multicomponent vaccine, phosphate buffer, sucrose, and polysorbate 80.

[0159] In one aspect, the disclosure provides a spray freeze-dried pharmaceutical composition comprising a multicomponent vaccine, histidine-borate, phosphate buffer, sucrose, and polysorbate 80.

[0160] In one aspect, the disclosure provides a spray freeze-dried pharmaceutical composition comprising a multicomponent vaccine, tris buffer, sucrose, and polysorbate 80.

[0161] In one aspect, the disclosure provides a spray freeze-dried pharmaceutical composition comprising a multicomponent vaccine, histidine-borate, tris buffer, sucrose, and polysorbate 80.

[0162] In some embodiments, the multicomponent vaccine comprises: HlaH35LH48L, LukSmut9, LukFmutl, TBA225 and LukABmut50.

[0163] In some embodiments, HlaH35LH48L comprises a Hla toxoid with H35L and H48L mutations. In some embodiments, HlaH35LH48L comprises the amino acid sequence of SEQ ID NO: 1. In some embodiments, HlaH35LH48L consists of the amino acid sequence of SEQ ID NO: 1.

[0164] In some embodiments, LukSmut9 comprises the S subunit of a PVL toxoid with T28F, K97A, and S209A mutations. In some embodiments, LukSmut9 comprises comprises the amino acid sequence of SEQ ID NO: 2. In some embodiments, LukSmut9 consists of the amino acid sequence of SEQ ID NO: 2.

[0165] In some embodiments, LukFmutl comprises the F subunit of a PVL toxoid with K102A mutation. In some embodiments, LukFmutl comprises the amino acid sequence of SEQ ID NO: 3. In some embodiments, LukFmutl consists of the amino acid sequence of SEQ ID NO: 3.

[0166] In some embodiments, LukABmut50 comprises a dimeric toxoid form of LukAB with D39A mutation in LukA and R23E mutation in LukB. In some embodiments, LukABmut50 comprises a variant of LukA comprising D39A mutation in LukA and a variant of LukB comprising R23E mutation in LukB. In some embodiments, LukABmut50 comprises a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO:5. In some embodiments, LukABmut50 comprises a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5.

[0167] In some embodiments, TBA225 comprises a fusion protein comprising: (1) a TSST-1 toxoid with L30R, D27A, and I46A mutations, (2) a SEB toxoid with L45R, Y89A, and Y94A mutations, and (3) a SEA toxoid with L48R, D70R, Y92A, and H225A mutations. In some embodiments, the three toxoids are fused together via a linker. In some embodiemnts, the linker comprise the amino acid sequence of GGGSGGGSGGGS (SEQ ID NO: 7). In some embodiments, TBA225 comprises the amino acid sequence of SEQ ID NO: 6. In some embodiments, TBA225 consists of the amino acid sequence of SEQ ID NO: 6.

[0168] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about from 0.005 mg / ml to 10 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is from 0.005 mg / ml to 10 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about from 0.01 mg / ml to 10 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is from 0.01 mg / ml to 10 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about from 0.05 mg / ml to 5 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is from 0.05 mg / ml to 5 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about from 0.1 mg / ml to 1 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is from 0.1 mg / ml to 1 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about from 0.2 mg / ml to 0.5 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is from 0.2 mg / ml to 0.5 mg / ml uponreconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about from 0.4 mg / ml to 0.5 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is from 0.4 mg / ml to 0.5 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is at least 0.005 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is at least 0.01 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is at least 0.025 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is at least 0.05 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is at least 0.1 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is at most 10 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is at most 7.5 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is at most 5 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is at most 2.5 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is at most 1 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about 1 mg / ml, 0.9 mg / ml, 0.8 mg / ml, 0.7 mg / ml, 0.6 mg / ml, 0.5 mg / ml, 0.4 mg / ml, 0.3 mg / ml, 0.2 mg / ml, 0.1 mg / ml, 0.09 mg / ml, 0.08mg / ml, 0.075 mg / ml, 0.07 mg / ml, 0.06 mg / ml, 0.05 mg / ml, 0.04 mg / ml, 0.03 mg / ml, 0.025 mg / ml, 0.02 mg / ml, 0.01 mg / ml, 0.009 mg / ml, 0.008 mg / ml, 0.007 mg / ml, 0.00625 mg / ml, or 0.005 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is of 1 mg / ml, 0.9 mg / ml, 0.8 mg / ml, 0.7 mg / ml, 0.6 mg / ml, 0.5 mg / ml, 0.4 mg / ml, 0.3 mg / ml, 0.2 mg / ml, 0.1 mg / ml, 0.09 mg / ml, 0.08 mg / ml, 0.075 mg / ml, 0.07 mg / ml, 0.06 mg / ml, 0.05 mg / ml, 0.04 mg / ml, 0.03 mg / ml, 0.025 mg / ml, 0.02 mg / ml, 0.01 mg / ml, 0.009 mg / ml, 0.008 mg / ml, 0.007 mg / ml, 0.00625 mg / ml, or 0.005 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about 0.4 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is 0.4 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about 0.3 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is 0.3 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about 0.2 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is 0.2 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about 0.1 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is 0.1 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about 0.075 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is 0.075 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the sprayfreeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about 0.05 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is 0.05 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about 0.025 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is 0.025 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about 0.01 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is 0.01 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about 0.00625 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is 0.00625 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is about 0.005 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the total protein of the vaccine is 0.005 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 500 pg per dose, 450 pg per dose, 400 pg per dose, 350 pg per dose, 300 pg per dose, 250 pg per dose, 200 pg per dose, 150 pg per dose, 100 pg per dose, 50 pg per dose, 45 pg per dose, 40 pg per dose, 37.5 pg per dose, 35 pg per dose, 30 pg per dose, 25 pg per dose, 20 pg per dose, 15 pg per dose, 12.5 pg per dose, 10 pg per dose, 5 pg per dose, 4.5 pg per dose, 4 pg per dose, 3.5 pg per dose, 3.125 pg per dose, or 2.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is 500 pg per dose, 450 pg per dose, 400 pg per dose, 350 pg per dose, 300 pg per dose, 250 pg per dose, 200 pg per dose, 150 pg per dose, 100pg per dose, 50 pg per dose, 45 pg per dose, 40 pg per dose, 37.5 pg per dose, 35 pg per dose, 30 pg per dose, 25 pg per dose, 20 pg per dose, 15 pg per dose, 12.5 pg per dose, 10 pg per dose, 5 pg per dose, 4.5 pg per dose, 4 pg per dose, 3.5 pg per dose, 3.125 pg per dose, or 2.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 200 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is 200 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 175 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is 175 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 150 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is 150 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 100 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is 100 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 75 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is 75 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 50 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is 50 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 25 pg per dose. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, the total protein of the vaccine is 25 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 12.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is 12.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 10 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of thevaccine is 10 jj.g per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is 5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 3.125 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is 3.125 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 2.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is 2.5 pg per dose.

[0169] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is about the same. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is the same. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is about from 0.001 mg / ml to 2 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is from 0.001 mg / ml to 2 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is about from 0.002 mg / ml to 2 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is from 0.002 mg / ml to 2 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is about from 0.01 mg / ml to 1 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is from 0.01 mg / ml to 1 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is about from 0.02 mg / ml to 0.2 mg / ml upon reconstitution in a liquid formulation. In someembodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is from 0.02 mg / ml to 0.2 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is about from 0.04 mg / ml to 0.1 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is from 0.04 mg / ml to 0.1 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is about from 0.08 mg / ml to 0.1 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is from 0.08 mg / ml to 0.1 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is at least 0.001 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is at least 0.002 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is at least 0.005 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is at least 0.01 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is at least 0.02 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is at most 2 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is at most 1.5 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is at most 1 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-driedpharmaceutical composition provided herein, the concentration of each component of the vaccine is at most 0.5 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is at most 0.2 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is about 0.2 mg / ml, 0.18 mg / ml, 0.16 mg / ml, 0.14 mg / ml, 0.12 mg / ml, 0.1 mg / ml, 0.08 mg / ml, 0.06 mg / ml, 0.04 mg / ml, 0.02 mg / ml, 0.018 mg / ml, 0.016 mg / ml, 0.025 mg / ml, 0.014 mg / ml, 0.012 mg / ml, 0.01 mg / ml, 0.008 mg / ml, 0.006 mg / ml, 0.005 mg / ml, 0.004 mg / ml, 0.002 mg / ml, 0.0018 mg / ml, 0.0016 mg / ml, 0.0014 mg / ml, 0.00125 mg / ml, or 0.001 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is 0.2 mg / ml, 0.18 mg / ml, 0.16 mg / ml, 0.14 mg / ml, 0.12 mg / ml, 0.1 mg / ml, 0.08 mg / ml, 0.06 mg / ml, 0.04 mg / ml, 0.02 mg / ml, 0.018 mg / ml, 0.016 mg / ml, 0.025 mg / ml, 0.014 mg / ml, 0.012 mg / ml, 0.01 mg / ml, 0.008 mg / ml, 0.006 mg / ml, 0.005 mg / ml, 0.004 mg / ml, 0.002 mg / ml, 0.0018 mg / ml, 0.0016 mg / ml, 0.0014 mg / ml, 0.00125 mg / ml, or 0.001 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is about 0.08 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein the concentration of each component of the vaccine is 0.08 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is about 0.06 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein the concentration of each component of the vaccine is 0.06 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is about 0.04 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein the concentration of each component of the vaccine is 0.04 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each competent of the vaccine is about 0.04 mg per dose. In some embodimentsof the spray freeze-dried pharmaceutical composition provided herein, each competent of the vaccine is 0.04 mg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is about 0.02 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is 0.02 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is about 0.015 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is 0.015 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is about 0.01 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is 0.01 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is about 0.005 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is 0.005 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is about 0.002 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is 0.002 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is about 0.00125 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is 0.00125 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of each component of the vaccine is about 0.001 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-driedpharmaceutical composition provided herein, the concentration of each component of the vaccine is 0.001 mg / ml upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 100 pg per dose, 90 pg per dose, 80 pg per dose, 70 pg per dose, 60 pg per dose, 50 pg per dose, 40 pg per dose, 30 pg per dose, 20 pg per dose, 10 pg per dose, 9 pg per dose, 8 pg per dose, 7.5 pg per dose, 5 pg per dose, 6 pg per dose, 5 pg per dose, 4 pg per dose, 3 pg per dose, 2.5 pg per dose, 2 pg per dose, 1 pg per dose, 0.9 pg per dose, 0.8 pg per dose, 0.7 pg per dose, 0.625 pg per dose, or 0.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 100 pg per dose, 90 pg per dose, 80 pg per dose, 70 pg per dose, 60 pg per dose, 50 pg per dose, 40 pg per dose, 30 pg per dose, 20 pg per dose, 10 pg per dose, 9 pg per dose, 8 pg per dose, 7.5 pg per dose, 5 pg per dose, 6 pg per dose, 5 pg per dose, 4 pg per dose, 3 pg per dose, 2.5 pg per dose, 2 pg per dose, 1 pg per dose, 0.9 pg per dose, 0.8 pg per dose, 0.7 pg per dose, 0.625 pg per dose, or 0.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 40 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 40 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 35 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 35 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 30 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 30 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 20 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 20 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 15 pg per dose. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, each component of the vaccine is 15 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 10 pg per dose. In some embodiments of thespray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 10 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 2.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 2.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 2 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 2 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 1 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 1 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 0.625 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 0.625 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 0.5 pg per dose. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, each component of the vaccine is 0.5 pg per dose.

[0170] In some embodiments, the spray freeze-dried pharmaceutical composition provided herein does not comprise histidine-borate. In some embodiments, the spray freeze-dried pharmaceutical composition provided herein comprises histidine-borate. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of histidine-borate is about from O.lmM to 50mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of histidine-borate is from O.lmM to 50mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of histidine-borate is about from 0. ImM to 40mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-driedpharmaceutical composition provided herein, the concentration of histidine-borate is from O.lmM to 40mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of histidine-borate is about from 0. ImM to 30mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of histidine-borate is from 0. ImM to 30mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of histidine-borate is about from 5mM to 25 mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of histidine-borate is from 5mM to 25 mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of histidine-borate is about from lOmM to 25mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of histidine-borate is from lOmM to 25mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of histidine- borate is about from 15mM to 25mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of histidine-borate is from 15mM to 25mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of histidine-borate is at least 0. ImM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of histidine-borate is at least 0.5mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of histidine-borate is at least ImM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of histidine-borate is at least 5mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of histidine-borate is at most 50mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of histidine-borate is at most 40mM upon reconstitution in aliquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of histidine-borate is at most 35mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of histidine-borate is about 15mM, 16 mM, 17 mM, 18 mM, 19 mM, 20 mM, 21 mM, 22 mM, 23 mM, 24 mM, 25 mM, 26 mM, 27 mM, 28 mM, 29 mM, 30 mM, 31 mM, 32 mM, 33 mM, 34 mM, or 35 mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of histidine-borate is ofl5mM, 16 mM, 17 mM, 18 mM, 19 mM, 20 mM, 21 mM, 22 mM, 23 mM, 24 mM, 25 mM, 26 mM, 27 mM, 28 mM, 29 mM, 30 mM, 31 mM, 32 mM, 33 mM, 34 mM, or 35 mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of histidine- borate is about 25mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of histidine- borate is 25mM upon reconstitution in a liquid formulation.

[0171] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the buffer is about from O.lmM to 30mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the buffer is from O.lmM to 30mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the buffer is about from 0.2mM to 20mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the buffer is from 0.2mM to 20mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, the concentration of the buffer is about from 0.5mM to 20mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the buffer is from 0.5mM to 20mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the buffer is about from 0.5mM to lOmM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the buffer is from 0.5mM to lOmM upon reconstitution in a liquid formulation. In some embodiments of thespray freeze-dried pharmaceutical composition provided herein, the concentration of the buffer is about from ImM to 5mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the buffer is from ImM to 5mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the buffer is about from ImM to 3mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the buffer is from ImM to 3mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the buffer is at least O.lmM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the buffer is at least 0.2mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the buffer is at least 0.5mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the buffer is at least 0.75mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the buffer is at least ImM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the buffer is at most 30mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the buffer is at most 20mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the buffer is at most lOmM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the buffer is at most 5mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the buffer is at most 3mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the buffer is about 0.5 mM, 0.6 mM, 0.7 mM, 0.8 mM, 0.9 mM, 1 mM, 1.1 mM, 1.2 mM, 1.3 mM, 1.4 mM, 1.5 mM, 1.6 mM, 1.7 mM, 1.8 mM, 1.9 mM, 2.0 mM, 2.1 mM, 2.2mM, 2.3 mM, 2.4 mM, 2.5 mM, 2.6 mM, 2.7 mM, 2.8 mM, 2.9 mM, or 3mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the buffer is of 0.5 mM, 0.6 mM, 0.7 mM, 0.8 mM, 0.9 mM, 1 mM, 1.1 mM, 1.2 mM, 1.3 mM, 1.4 mM, 1.5 mM, 1.6 mM, 1.7 mM, 1.8 mM, 1.9 mM, 2.0 mM, 2.1 mM, 2.2 mM, 2.3 mM, 2.4 mM, 2.5 mM, 2.6 mM, 2.7 mM, 2.8 mM, 2.9 mM, or 3mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the buffer is about 2mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the buffer is 2mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the buffer is about 1.2mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the buffer is 1.2mM upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the buffer is phosphate buffer. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the buffer is tris buffer.

[0172] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the stabilizer is about from 1% (weight / volume, 10 g / L) to 30% (weight / volume, 300 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the stabilizer is from 1% (weight / volume, 10 g / L) to 30% (weight / volume, 300 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the stabilizer is about from 2% (weight / volume, 20 g / L) to 20% (weight / volume, 200 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the stabilizer is from 2% (weight / volume, 20 g / L) to 20% (weight / volume, 200 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the stabilizer is about from 2% (weight / volume, 20 g / L) to 15% (weight / volume, 150 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-driedpharmaceutical composition provided herein, the concentration of the stabilizer is from 2% (weight / volume, 20 g / L) to 15% (weight / volume, 150 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the stabilizer is about from 2% (weight / volume, 20 g / L) to 10% (weight / volume, 100 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the stabilizer is from 2% (weight / volume, 20 g / L) to 10% (weight / volume, 100 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the stabilizer is about from 5% (weight / volume, 50 g / L) to 10% (weight / volume, 100 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the stabilizer is from 5% (weight / volume, 50 g / L) to 10% (weight / volume, 100 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the stabilizer is at least 1% (weight / volume, 10 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the stabilizer is at least 2% (weight / volume, 20 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the stabilizer is at least 3% (weight / volume, 30 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the stabilizer is at least 4% (weight / volume, 40 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the stabilizer is at least 5% (weight / volume, 50 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the stabilizer is at most 30% (weight / volume, 300 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the stabilizer is at most 25% (weight / volume, 250 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the stabilizer is at most 20% (weight / volume, 200 g / L) upon reconstitution in a liquid formulation. In some embodiments ofthe spray freeze-dried pharmaceutical composition provided herein, the concentration of the stabilizer is at most 15% (weight / volume, 150 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the stabilizer is about 1% (weight / volume, 10 g / L), 2% (weight / volume, 20 g / L), 3%(weight / volume, 30 g / L), 4%(weight / volume, 40 g / L), 5%(weight / volume, 50 g / L), 6%(weight / volume, 60 g / L), 7%(weight / volume, 70 g / L), 8%(weight / volume, 80 g / L), 9%(weight / volume, 90 g / L), 10%(weight / volume, 100 g / L), 1 l%(weight / volume, 110 g / L), 12%(weight / volume, 120 g / L), 13%(weight / volume, 130 g / L), 14%(weight / volume, 140 g / L), 15%(weight / volume, 150 g / L), 16%(weight / volume, 160 g / L), 17%(weight / volume, 170 g / L), 18%(weight / volume, 180 g / L), 19%(weight / volume, 190 g / L), or 20% (weight / volume, 200 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the stabilizer is of 1% (weight / volume, 10 g / L), 2% (weight / volume, 20 g / L), 3%(weight / volume, 30 g / L), 4%(weight / volume, 40 g / L), 5%(weight / volume, 50 g / L), 6%(weight / volume, 60 g / L), 7%(weight / volume, 70 g / L), 8%(weight / volume, 80 g / L), 9%(weight / volume, 90 g / L), 10%(weight / volume, 100 g / L), 1 l%(weight / volume, 110 g / L), 12%(weight / volume, 120 g / L), 13%(weight / volume, 130 g / L), 14%(weight / volume, 140 g / L), 15%(weight / volume, 150 g / L), 16%(weight / volume, 160 g / L), 17%(weight / volume, 170 g / L), 18%(weight / volume, 180 g / L), 19%(weight / volume, 190 g / L), or 20% (weight / volume, 200 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the stabilizer is about 8% (weight / volume, 80 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the stabilizer is 8% (weight / volume, 80 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the stabilizer is sucrose.

[0173] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the surfactant is about from 0.004% (weight / volume, 0.04 g / L) to 2% (weight / volume, 20 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the surfactant is from 0.004% (weight / volume, 0.04 g / L) to 2% (weight / volume, 20 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-driedpharmaceutical composition provided herein, the concentration of the surfactant is about from 0.01% (weight / volume, 0.1 g / L) to 0.5% (weight / volume, 5 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the surfactant is from 0.01% (weight / volume, 0.1 g / L) to 0.5% (weight / volume, 5 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the surfactant is about from 0.01% (weight / volume, 0.1 g / L) to 0.1% (weight / volume, 1 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the surfactant is from 0.01% (weight / volume, 0.1 g / L) to 0.1% (weight / volume, 1 g / L) upon reconstitution in a liquid formulation. . In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the surfactant is about from 0.01% (weight / volume, 0.1 g / L) to 0.05% (weight / volume, 0.5 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the surfactant is from 0.01% (weight / volume, 0.1 g / L) to 0.05% (weight / volume, 0.5 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the surfactant is at least 0.004% (weight / volume, 0.04 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the surfactant is at least 0.006% (weight / volume, 0.06 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the surfactant is at least 0.008% (weight / volume, 0.08 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the surfactant is at least 0.01% (weight / volume, 0.1 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the surfactant is at most 2% (weight / volume, 20 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the surfactant is at most 1.5% (weight / volume, 15 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of thesurfactant is at most 1% (weight / volume, 10 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the surfactant is about 0.005% (weight / volume, 0.05 g / L), 0.01% (weight / volume, 0.1 g / L), 0.015% (weight / volume, 0.15 g / L), 0.02% (weight / volume, 0.2 g / L), 0.03% (weight / volume, 0.3 g / L), 0.04% (weight / volume, 0.4 g / L), 0.05% (weight / volume, 0.5 g / L), 0.06% (weight / volume, 0.6 g / L), 0.07% (weight / volume, 0.7 g / L), 0.08% (weight / volume, 0.8 g / L), 0.09% (weight / volume, 0.9 g / L), or 0.1% (weight / volume, 1.0 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the surfactant is of 0.005% (weight / volume, 0.05 g / L), 0.01% (weight / volume, 0.1 g / L), 0.015% (weight / volume, 0.15 g / L), 0.02% (weight / volume, 0.2 g / L), 0.03% (weight / volume, 0.3 g / L), 0.04% (weight / volume, 0.4 g / L), 0.05% (weight / volume, 0.5 g / L), 0.06% (weight / volume, 0.6 g / L), 0.07% (weight / volume, 0.7 g / L), 0.08% (weight / volume, 0.8 g / L), 0.09% (weight / volume, 0.9 g / L), or 0.1% (weight / volume, 1.0 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, the concentration of the surfactant is about 0.02% (weight / volume, 0.2 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the concentration of the surfactant is 0.02% (weight / volume, 0.2 g / L) upon reconstitution in a liquid formulation. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the surfactant is polysorbate 20 or polysorbate 80. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the surfactant is polysorbate 80.

[0174] In certain embodiments, the pH of the spray freeze-dried pharmaceutical composition is about from 6.0 to 9.0 upon reconstitution in a liquid formulation. In certain embodiments, the pH of the spray freeze-dried pharmaceutical composition is about 6, 6.5, 7, 7.5, 8, 8.5 or 9 upon reconstitution in a liquid formulation. In some embodiments, the pH of the spray freeze-dried pharmaceutical composition is about 7.5 upon reconstitution in a liquid formulation. In certain embodiments, the pH of the spray freeze-dried pharmaceutical composition is from 6.0 to 9.0 upon reconstitution in a liquid formulation. In certain embodiments, the pH of the spray freeze- dried pharmaceutical composition is 6, 6.5, 7, 7.5, 8, 8.5 or 9 upon reconstitution in a liquid formulan. In certain embodiments, the pH of the spray freeze-dried pharmaceutical composition is 7.5 upon reconstitution in a liquid formulation.

[0175] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the spray freeze-dried pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 2: 400: 1 by weight. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the spray freeze-dried pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 1.5: 400: 1 by weight. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the spray freeze-dried pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 1 : 400: 1 by weight. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the spray freeze-dried pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 0.75: 400: 1 by weight. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the spray freeze-dried pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 0.5: 400: 1 by weight. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the spray freeze-dried pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 0.25: 400: 1 by weight. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the spray freeze-dried pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 0.125: 400: 1 by weight. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the spray freeze-dried pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 0.03125: 400: 1 by weight. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the spray freeze-dried pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 0.025: 400: 1 by weight.

[0176] In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the spray freeze-dried pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at a ratio of 2: 400: 1 by weight. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, the spray freeze-dried pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at a ratio of 1.5: 400: 1 by weight. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the spray freeze-dried pharmaceutical composition comprises the total protein, sucrose,and polysorbate 80 at a ratio of 1 : 400: 1 by weight. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, the spray freeze-dried pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at a ratio of 0.75: 400: 1 by weight. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the spray freeze-dried pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at a ratio of 0.5: 400: 1 by weight. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, the spray freeze-dried pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at a ratio of 0.25: 400: 1 by weight. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the spray freeze-dried pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at a ratio of 0.125: 400: 1 by weight. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the spray freeze-dried pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at a ratio of 0.03125: 400: 1 by weight. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the spray freeze-dried pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at a ratio of 0.025: 400: 1 by weight.

[0177] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) tris buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmutl comprising the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.4mg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 0.2 mg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 0.04 mg per dose. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, the total protein of the vaccine is 0.2 mg perdose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 0.04 mg per dose.

[0178] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) tris buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmutl consisting of the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.4mg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 0.2 mg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 0.04 mg per dose. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, the total protein of the vaccine is 0.2 mg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 0.04 mg per dose.

[0179] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) tris buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmutl comprising the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.4mg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the totalprotein of the vaccine is about 0.2 mg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 0.04 mg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is 0.2 mg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 0.04 mg per dose.

[0180] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) tris buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmutl consisting of the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.4mg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 0.2 mg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 0.04 mg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is 0.2 mg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 0.04 mg per dose.

[0181] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) phosphate buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmutl comprising the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a firstpolypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.4mg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 0.2 mg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 0.04 mg per dose. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, the total protein of the vaccine is 0.2 mg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 0.04 mg per dose.

[0182] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) phosphate buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmutl consisting of the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.4mg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 0.2 mg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 0.04 mg per dose. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, the total protein of the vaccine is 0.2 mg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 0.04 mg per dose.

[0183] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) phosphate buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) afterreconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmutl comprising the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.4mg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 0.2 mg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 0.04 mg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is 0.2 mg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 0.04 mg per dose.

[0184] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) phosphate buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmutl consisting of the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.4mg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 0.2 mg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 0.04 mg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is 0.2 mg per dose. In some embodiments of the sprayfreeze-dried pharmaceutical composition provided herein, each component of the vaccine is 0.04 mg per dose.

[0185] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) tris buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmutl comprising the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of O.lmg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 50 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 10 pg per dose. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, the total protein of the vaccine is 50 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 10 pg per dose.

[0186] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) tris buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmutl consisting of the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of O.lmg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 50 pg per dose. In someembodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 10 pg per dose. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, the total protein of the vaccine is 50 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 10 pg per dose.

[0187] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) tris buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmutl comprising the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0. Img / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 50 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 10 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is 50 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 10 pg per dose.

[0188] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) tris buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmutl consisting of the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide consisting of the amino acidsequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of O.lmg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 50 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 10 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is 50 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 10 pg per dose.

[0189] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) phosphate buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmutl comprising the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of O.lmg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 50 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 10 pg per dose. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, the total protein of the vaccine is 50 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 10 pg per dose.

[0190] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) phosphate buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein themulticomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmutl consisting of the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of O.lmg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 50 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 10 pg per dose. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, the total protein of the vaccine is 50 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 10 pg per dose.

[0191] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) phosphate buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmutl comprising the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0. Img / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 50 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 10 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is 50 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 10 pg per dose.

[0192] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) phosphate buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmutl consisting of the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0. Img / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 50 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 10 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is 50 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 10 pg per dose.

[0193] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) tris buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmutl comprising the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.025mg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 12.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, eachcomponent of the vaccine is about 2.5 pg per dose. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, the total protein of the vaccine is 12.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 2.5 pg per dose.

[0194] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) tris buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmutl consisting of the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.025mg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 12.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 2.5 pg per dose. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, the total protein of the vaccine is 12.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 2.5 pg per dose.

[0195] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) tris buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmutl comprising the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein thetotal protein of the multicomponent vaccine is at the concentration of 0.025mg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 12.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 2.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is 12.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 2.5 pg per dose.

[0196] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) tris buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmutl consisting of the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.025mg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 12.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 2.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is 12.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 2.5 pg per dose.

[0197] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) phosphate buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmutl comprising the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.025mg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 12.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 2.5 pg per dose. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, the total protein of the vaccine is 12.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 2.5 pg per dose.

[0198] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) phosphate buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmutl consisting of the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.025mg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 12.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 2.5 pg per dose. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, the total protein of the vaccine is 12.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 2.5 pg per dose.

[0199] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) phosphatebuffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmutl comprising the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.025mg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 12.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 2.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is 12.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 2.5 pg per dose.

[0200] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) phosphate buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmutl consisting of the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.025mg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 12.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 2.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition providedherein, the total protein of the vaccine is 12.5 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 2.5 pg per dose.

[0201] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) tris buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmutl comprising the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.00625mg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 3.125 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 0.625 pg per dose. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, the total protein of the vaccine is 3.125 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 0.625 pg per dose.

[0202] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) tris buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmutl consisting of the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.00625mg / ml. In some embodiments of the spray freeze-dried pharmaceuticalcomposition provided herein, the total protein of the vaccine is about 3.125 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 0.625 pg per dose. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, the total protein of the vaccine is 3.125 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 0.625 pg per dose.

[0203] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) tris buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmutl comprising the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.00625mg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 3.125 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 0.625 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is 3.125 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 0.625 pg per dose.

[0204] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) tris buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmutl consisting of the amino acid sequence ofI l lSEQ ID NO: 3, LukABmut50 comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.00625mg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 3.125 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 0.625 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is 3.125 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 0.625 pg per dose.

[0205] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) phosphate buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmutl comprising the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.00625mg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 3.125 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 0.625 pg per dose. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, the total protein of the vaccine is 3.125 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 0.625 pg per dose.

[0206] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) phosphate buffer at the concentration of 1.2mM, (3) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (4) polysorbate 80 at the concentration of0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmutl consisting of the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.00625mg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 3.125 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 0.625 pg per dose. In some embodiments of the spray freeze- dried pharmaceutical composition provided herein, the total protein of the vaccine is 3.125 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 0.625 pg per dose.

[0207] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) phosphate buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L comprising the amino acid sequence of SEQ ID NO: 1, LukSmut9 comprising the amino acid sequence of SEQ ID NO: 2, LukFmutl comprising the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5, TBA225 comprising the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.00625mg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 3.125 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 0.625 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is 3.125 pg per dose. In some embodiments of the sprayfreeze-dried pharmaceutical composition provided herein, each component of the vaccine is 0.625 pg per dose.

[0208] In some embodiments, the spray freeze-dried pharmaceutical composition consists of: (1) a multicomponent vaccine, (2) histidine-borate at the concentration of 25mM, (3) phosphate buffer at the concentration of 1 ,2mM, (4) sucrose at the concentration of 8% (weight / volume, 80 g / L), and (5) polysorbate 80 at the concentration of 0.02% (weight / volume, 0.2 g / L) after reconstitution in a liquid formulation, wherein the multicomponent vaccine comprises: HlaH35LH48L consisting of the amino acid sequence of SEQ ID NO: 1, LukSmut9 consisting of the amino acid sequence of SEQ ID NO: 2, LukFmutl consisting of the amino acid sequence of SEQ ID NO: 3, LukABmut50 comprising a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5, TBA225 consisting of the amino acid sequence of SEQ ID NO: 6, and wherein the total protein of the multicomponent vaccine is at the concentration of 0.00625mg / ml. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is about 3.125 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is about 0.625 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, the total protein of the vaccine is 3.125 pg per dose. In some embodiments of the spray freeze-dried pharmaceutical composition provided herein, each component of the vaccine is 0.625 pg per dose.

[0209] In some embodiments, the spray freeze-dried pharmaceutical composition comprises a residual moisture content between about 1% and about 7%. In some embodiments, the spray freeze-dried pharmaceutical composition comprises a residual moisture content between about 2% and about 6%. In some embodiments, the spray freeze-dried pharmaceutical composition comprises a residual moisture content between about 3% and about 5%. In some embodiments, the spray freeze-dried pharmaceutical composition comprises a residual moisture content about 3%. In some embodiments, the spray freeze-dried pharmaceutical composition comprises a residual moisture content about 4%. In some embodiments, the spray freeze-dried pharmaceutical composition comprises a residual moisture content about 5%. In some embodiments, the spray freeze-dried pharmaceutical composition comprises a residual moisture content between 1% and 7%. In some embodiments, the spray freeze-dried pharmaceuticalcompositio...

Claims

WHAT IS CLAIMED:

1. A lyophilized pharmaceutical composition comprising: a. a multicomponent vaccine, b. a buffer, c. sucrose, and d. polysorbate 80, wherein the multicomponent vaccine comprises: HlaH35LH48L, LukSmut9, LukFmuti, TBA225 and LukABmutso.

2. The lyophilized pharmaceutical composition of claim 1, wherein the composition further comprises histidine-borate.

3. The lyophilized pharmaceutical composition of claim 1 or 2, wherein the buffer is phosphate buffer.

4. The lyophilized pharmaceutical composition of any one of claims 1 to 3, wherein a. Hlau35LH48L comprises a Hla toxoid with H35L and H48L mutations, or comprises the amino acid sequence of SEQ ID NO: 1; b. LukSmut9 comprises the S subunit of a PVL toxoid with T28F, K97A, and S209A mutations, or comprises the amino acid sequence of SEQ ID NO: 2; c. LukFmuti comprises the F subunit of a PVL toxoid with K102A mutation, or comprises the amino acid sequence of SEQ ID NO: 3; d. LukABmutso comprises a dimeric toxoid form of LukAB with D39A mutation in LukA and R23E mutation in LukB, or comprises a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5; e. TBA225 comprises a fusion protein comprising: i. a TSST-1 toxoid with L30R, D27A, and 146 A mutations, ii. a SEB toxoid with L45R, Y89A, and Y94A mutations, and iii. a SEA toxoid with L48R, D70R, Y92A, and H225A mutations; orcomprising the amino acid sequence of SEQ ID NO: 6;5. The lyophilized pharmaceutical composition of claim 4, wherein a. HlaH35LH48L consists of the amino acid sequence of SEQ ID NO: 1; b. LukSmut9 consists of the amino acid sequence of SEQ ID NO: 2; c. LukFmuti consists of the amino acid sequence of SEQ ID NO: 3; d. LukABmutso comprises a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5; and e. TBA225 consists of the amino acid sequence of SEQ ID NO: 6.

6. The lyophilized pharmaceutical composition of any one of claims 1 to 5, wherein the concentration of the total protein of the vaccine is about from 0.005 mg / ml to 10 mg / ml after reconstitution in a liquid formulation.

7. The lyophilized pharmaceutical composition of any one of claims 1 to 6, wherein the concentration of each component of the vaccine is about from 0.001 mg / ml to 2 mg / ml after reconstitution in a liquid formulation.

8. The lyophilized pharmaceutical composition of any one of claims 1 to 7, wherein the concentration of sucrose is about from 2% (weight / volume, 20 g / L) to 10% (weight / volume, 100 g / L) after reconstitution in a liquid formulation.

9. The lyophilized pharmaceutical composition of any one of claims 1 to 8, wherein the concentration of polysorbate 80 is about from 0.004% (weight / volume, 0.04 g / L) to 2% (weight / volume, 20 g / L) after reconstitution in a liquid formulation.

10. The lyophilized pharmaceutical composition of any one of claims 1 to 7, wherein the concentration of histidine-borate is about from O.lmM to 25mM after reconstitution in a liquid formulation.

11. The lyophilized pharmaceutical composition of any one of claims 3 to 10, wherein the concentration of phosphate buffer is about from 0.5mM to 20mM after reconstitution in a liquid formulation.

12. The lyophilized pharmaceutical composition of any one of claims 1 to 5, wherein the lyophilized pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at about a ratio of 2: 400: 1 by weight.

13. The lyophilized pharmaceutical composition of any one of claims 1 to 11, wherein the concentration of the total protein is about 0.4 mg / ml, the concentration of the histidine-borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of the polysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5 after reconstitution in a liquid formulation.

14. The lyophilized pharmaceutical composition of any one of claims 1 to 9, wherein the total protein is about 200 pg per dose.

15. The lyophilized pharmaceutical composition of any one of claims 1 to 12, wherein the multivalent vaccine has at least about 2%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, or at least about 50% less protein aggregation or degradation compared with a multivalent vaccine with the same composition that is formulated at the same concentration in a liquid formulation.

16. The lyophilized pharmaceutical composition of claim 15, wherein the protein aggregation or degradation is measured by SEC-HPLC, SDS-PAGE or Western blot assay.

17. The lyophilized pharmaceutical composition of any one of claims 1 to 14, wherein the multivalent vaccine has similar immunogenic activity compared with a multivalent vaccine with the same components that is formulated at the same concentration in a liquid formulation.

18. The lyophilized pharmaceutical composition of claim 17, wherein the immunogenic activity is measured by the levels of antibody titers production in a subject induced by administering to the subject the multivalent vaccine in a lyophilized or liquid formulation.

19. The lyophilized pharmaceutical composition of any one of claims 1 to 18, wherein the increase in the amount of aggregated or degraded protein in the composition is less than 15%, 10%, 5%, or 2% after storage at -20°C for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.

20. The lyophilized pharmaceutical composition of any one of claims 1 to 18, wherein the increase in the amount of aggregated or degraded protein in the composition is less than 15%, 10%, 5%, or 2% after storage at 30°C for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.

21. The lyophilized pharmaceutical composition of any one of claims 1 to 18, wherein the multivalent vaccine retains at least 70% , 80%, 90% or 95% of its initial immunogenic activity after storage at -20°C for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.

22. The lyophilized pharmaceutical composition of any one of claims 1 to 18, wherein the multivalent vaccine retains at least 70% , 80%, 90% or 95% of its initial immunogenic activity after storage at 30°C for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months,about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.

23. A method of generating the lyophilized pharmaceutical composition of any one of claims 1 to 22, comprising: a. dissolving the multicomponent vaccine, sucrose, and polysorbate 80 in a suitable solvent to form a liquid composition; b. freezing the liquid composition to form a frozen composition; c. drying the frozen composition under a primary reduced pressure at a primary drying temperate for a period of time effective to reduce the moisture content of the composition; and d. further drying the frozen composition under a second reduced pressure at a second drying temperature for a period of time effective to further reduce the moisture content of the composition, thereby producing the lyophilized composition.

24. The method of claim 23, wherein the method comprises: a. dissolving the multicomponent vaccine, sucrose, and polysorbate 80 in a suitable solvent to form a liquid composition; b. freezing the liquid composition at -40°C for 2 hours to form a frozen composition; annealing the frozen composition at -25°C for 2 hours; and further freezing the frozen composition at -40°C for 1 hour. c. drying the frozen composition under a primary reduced pressure at -40°C for 0.5 hour to reduce the moisture content of the composition; and d. further drying the frozen composition under a second reduced pressure at 10°C for 1 hour to further reduce the moisture content of the composition, thereby producing the lyophilized composition.

25. The method of claim 23 or 24, wherein the lyophilized pharmaceutical composition has a final moisture content of between 3% and 5%.

26. A spray freeze-dried pharmaceutical composition comprising:a. a multicomponent vaccine, b. a buffer, c. sucrose, and d. polysorbate 80, wherein the multicomponent vaccine comprises: EHaH35LH48L, LukSmut9, LukFmuti, TBA225 and LukABmutso.

27. The spray freeze-dried pharmaceutical composition of claim 26, wherein the composition further comprises histidine-borate.

28. The spray freeze-dried pharmaceutical composition of claim 26 or 27, wherein the buffer is phosphate buffer.

29. The spray freeze-dried pharmaceutical composition of any one of claims 26 to 28, wherein: a. Hlau35LH48L comprises a Hla toxoid with H35L and H48L mutations, or comprises the amino acid sequence of SEQ ID NO: 1; b. LukSmut9 comprises the S subunit of a PVL toxoid with T28F, K97A, and S209A mutations, or comprises the amino acid sequence of SEQ ID NO: 2; c. LukFmuti comprises the F subunit of a PVL toxoid with K102A mutation, or comprises the amino acid sequence of SEQ ID NO: 3; d. LukABmutso comprises a dimeric toxoid form of LukAB with D39A mutation in LukA and R23E mutation in LukB, or comprises a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5; e. TBA225 comprises a fusion protein comprising: i. a TSST-1 toxoid with L30R, D27A, and 146 A mutations, ii. a SEB toxoid with L45R, Y89A, and Y94A mutations, and iii. a SEA toxoid with L48R, D70R, Y92A, and H225A mutations; or comprising the amino acid sequence of SEQ ID NO: 6.

30. The spray freeze-dried pharmaceutical composition of claim 29, wherein:a. HlaH35LH48L consists of the amino acid sequence of SEQ ID NO: 1; b. LukSmut9 consists of the amino acid sequence of SEQ ID NO: 2; c. LukFmuti consists of the amino acid sequence of SEQ ID NO: 3; d. LukABmutso comprises a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5; and e. TBA225 consists of the amino acid sequence of SEQ ID NO: 6.

31. The spray freeze-dried pharmaceutical composition of any one of claims 26 to 30, wherein the concentration of the total protein of the vaccine is about from 0.005 mg / ml to 10 mg / ml after reconstitution in a liquid formulation.

32. The spray freeze-dried pharmaceutical composition of any one of claims 26 to 31, wherein the concentration of each component of the vaccine is about from 0.001 mg / ml to 2 mg / ml after reconstitution in a liquid formulation.

33. The spray freeze-dried pharmaceutical composition of any one of claims 26 to 32, wherein the concentration of sucrose is from 2% (weight / volume, 20 g / L) to 10% (weight / volume, 100 g / L) after reconstitution in a liquid formulation.

34. The spray freeze-dried pharmaceutical composition of any one of claims 26 to 33, wherein the concentration of polysorbate 80 is about from 0.004% (weight / volume, 0.04 g / L) to 2% (weight / volume, 20 g / L) after reconstitution in a liquid formulation.

35. The spray freeze-dried pharmaceutical composition of any one of claims 27 to 32, wherein the concentration of histidine-borate is about from O.lmM to 25mM after reconstitution in a liquid formulation.

36. The spray freeze-dried pharmaceutical composition of any one of claims 28 to 35, wherein the concentration of phosphate buffer is about from 0.5mM to 20mM after reconstitution in a liquid formulation.

37. The spray freeze-dried pharmaceutical composition of any one of claims 26 to 36, wherein the spray freeze-dried pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at the ratio of 2: 400: 1 in weight.

38. The spray freeze-dried pharmaceutical composition of any one of claims 28 to 36, wherein the concentration of the total protein is about 0.4 mg / ml, the concentration of the histidine-borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of the polysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5 after reconstitution in a liquid formulation.

39. The spray freeze-dried pharmaceutical composition of any one of claims 28 to 36, wherein the total protein is about 200 pg per dose.

40. The spray freeze-dried pharmaceutical composition of any one of claims 26 to 39, wherein the multivalent vaccine has at least about 2%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, or at least about 50% less protein aggregation or degradation compared with a multivalent vaccine with the same composition that is formulated at the same concentration in a liquid formulation.

41. The spray freeze-dried pharmaceutical composition of claim 40, wherein the protein aggregation or degradation is measured by SEC-HPLC, SDS-PAGE or Western blot assay.

42. The spray freeze-dried pharmaceutical composition of any one of claims 26 to 39, wherein the multivalent vaccine has similar immunogenic activity compared with a multivalent vaccine with the same components that is formulated at the same concentration in a liquid formulation.

43. The spray freeze-dried pharmaceutical composition of claim 42, wherein the immunogenic activity is measured by the levels of antibody titers production in a subject inducedby administering to the subject the multivalent vaccine in a spray freeze-dried or liquid formulation.

44. The spray freeze-dried pharmaceutical composition of any one of claims 26 to 43, wherein the increase in the amount of aggregated or degraded protein in the composition is less than 15%, 10%, 5%, or 2% after storage at -20°C for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.

45. The spray freeze-dried pharmaceutical composition of any one of claims 26 to 43, wherein the increase in the amount of aggregated or degraded protein in the composition is less than 15%, 10%, 5%, or 2% after storage at 30°C for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.

46. The spray freeze-dried pharmaceutical composition of any one of claims 26 to 43, wherein the multivalent vaccine retains at least 70%, 80%, 90% or 95% of its initial immunogenic activity after storage at -20°C for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.

47. The spray freeze-dried pharmaceutical composition of any one of claims 26 to 43, wherein the multivalent vaccine retains at least 70% , 80%, 90% or 95% of its initial immunogenic activity after storage at 30°C for a period of time, wherein the period of time is about 1 weeks, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8months, about 9 months, about 10 months, about 11 months, about 12 months, about 15 months, about 18 months, or about 24 months.

48. A method of generating the spray freeze-dried pharmaceutical composition of any one of claims 26 to 47, comprising: a. dissolving the multicomponent vaccine, histidine-borate, phosphate buffer, sucrose, and polysorbate 80 in a suitable solvent to form a liquid composition; b. atomizing the liquid formulation into specifically sized spherical droplets; c. immediately freezing the droplets and locking in the size and shape of each individual particle; d. collecting the particles and drying the particles in bulk in a lyophilization chamber.

49. A reconstituted pharmaceutical composition of any one of claims 1 to 22, or 26 to 47 comprising: a. a multicomponent vaccine, b. a buffer, c. sucrose, d. polysorbate 80, and e. a reconstitution liquid wherein the multicomponent vaccine comprises: HlaH35LH48L, LukSmut9, LukFmuti, TBA225 and LukABmutso.

50. The reconstituted pharmaceutical composition of claim 49, wherein the composition further comprises histidine-borate.

51. The reconstituted pharmaceutical composition of claim 26 or 27, wherein the buffer is phosphate buffer.

52. The reconstituted pharmaceutical composition of any one of claims 49 to 51, whereina. HlaH35LH48L comprises a Hla toxoid with H35L and H48L mutations, or comprises the amino acid sequence of SEQ ID NO: 1; b. LukSmut9 comprises the S subunit of a PVL toxoid with T28F, K97A, and S209A mutations, or comprises the amino acid sequence of SEQ ID NO: 2; c. LukFmuti comprises the F subunit of a PVL toxoid with K102A mutation, or comprises the amino acid sequence of SEQ ID NO: 3; d. LukABmutso comprises a dimeric toxoid form of LukAB with D39A mutation in LukA and R23E mutation in LukB, or comprises a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 and a second polypeptide comprising the amino acid of sequence of SES ID NO: 5; e. TBA225 comprises a fusion protein comprising: i. a TSST-1 toxoid with L30R, D27A, and 146 A mutations, ii. a SEB toxoid with L45R, Y89A, and Y94A mutations, and iii. a SEA toxoid with L48R, D70R, Y92A, and H225A mutations; or comprising the amino acid sequence of SEQ ID NO: 6.

53. The reconstituted pharmaceutical composition of claim 52, wherein a. Hlau35LH48L consists of the amino acid sequence of SEQ ID NO: 1; b. LukSmut9 consists of the amino acid sequence of SEQ ID NO: 2; c. LukFmuti consists of the amino acid sequence of SEQ ID NO: 3; d. LukABmutso comprises a first polypeptide consisting of the amino acid sequence of SEQ ID NO: 4 and a second polypeptide consisting of the amino acid of sequence of SES ID NO: 5; and e. TBA225 consists of the amino acid sequence of SEQ ID NO: 6.

54. The reconstituted pharmaceutical composition of any one of claims 49 to 53, wherein the concentration of the total protein of the vaccine is about from 0.005 mg / ml to 10 mg / ml.

55. The reconstituted pharmaceutical composition of any one of claims 49 to 54, wherein the concentration of each component of the vaccine is about from 0.001 mg / ml to 2 mg / ml.

56. The reconstituted pharmaceutical composition of any one of claims 49 to 55, wherein the concentration of sucrose is about from 2% (weight / volume, 20 g / L) to 10% (weight / volume, 100 g / L).

57. The reconstituted pharmaceutical composition of any one of claims 49 to 56, wherein the concentration of polysorbate 80 is about from 0.004% (weight / volume, 0.04 g / L) to 2% (weight / volume, 20 g / L).

58. The reconstituted pharmaceutical composition of any one of claims 50 to 55, wherein the concentration of histidine-borate is about from O.lmM to 25mM.

59. The reconstituted pharmaceutical composition of any one of claims 51 to 58, wherein the concentration of phosphate buffer is about from 0.5mM to 20mM.

60. The reconstituted pharmaceutical composition of any one of claims 49 to 59, wherein the reconstituted pharmaceutical composition comprises the total protein, sucrose, and polysorbate 80 at the ratio of 2: 400: 1 in weight.

61. The reconstituted pharmaceutical composition of any one of claims 51 to 60, wherein the concentration of the total protein is about 0.4 mg / ml, the concentration of the histidine-borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of the polysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5.

62. The reconstituted pharmaceutical composition of any one of claims 51 to 61, wherein the total protein is about 200 pg per dose .

63. A method of treating or preventing Staphylococcus aureus (SA) infection in a subject, comprising administering to the subject the reconstituted pharmaceutical composition of any one of claims 49 to 62.

64. The method of claim 62, wherein the subject is a human subject.

65. A composition suitable for lyophilization or spray -freeze drying, comprising: a. a multicomponent vaccine, b. a buffer, c. sucrose, and d. polysorbate 80, wherein the multicomponent vaccine comprises: HlaH35LH48L, LukSmut9, LukFmuti, TBA225 and LukABmutso.

66. The composition of claim 65, wherein the composition further comprises histidine-borate.

67. The composition of claim 65 or 66, wherein the buffer is phosphate buffer.

68. The composition of any one of claims 65 to 67, wherein the composition comprises the total protein, sucrose, and polysorbate 80 at the ratio of 2: 400: 1 in weight.

69. The composition of claim 68, wherein the concentration of the total protein is about 0.4 mg / ml, the concentration of the histidine-borate is about 25mM, the concentration of the phosphate buffer is about 1.2mM, the concentration of the sucrose is about 8% (weight / volume, 80 g / L), the concentration of the polysorbate 80 is about 0.02% (weight / volume, 0.2 g / L), and the pH is 7.5.

70. The composition of claim 67, wherein the total protein is about 200 pg per dose.

71. A kit comprising one or more containers and instructions for use, wherein the one or more containers comprise the pharmaceutical composition of any one of claims 1 to 22, 26 to 47.