Immunogenic compositions for the prevention of herpes zoster

Abstract

The present disclosure provides immunogenic and vaccine compositions comprising a Varicella Zoster Virus (VZV) glycoprotein E (gE) antigen comprising SEQ ID NO: 2 and an SLA adjuvant for use in the prevention of herpes zoster.

Description

Docket No.: CURV-010 / 02WO 340277-2148 IMMUNOGENIC COMPOSITIONS FOR THE PREVENTION OF HERPES ZOSTER CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application is an international PCT application claiming priority to US Provisional Application Nos. 63 / 651,507, filed May 24, 2024, and 63 / 747,676, filed January 21, 2025, each of which are incorporated by reference herein in their entireties. REFERENCE TO THE ELECTRONIC SEQUENCE LISTING

[0002] The contents of the electronic sequence listing (CURV_010_02WO_SeqList_ST26.xml; Size: 3,839 bytes; and Date of Creation: May 23, 2025) are herein incorporated by reference in its entirety. BACKGROUND

[0003] Shingles (herpes zoster) is a blistering rash accompanied by severe pain, lasting 2-4 weeks, which 30% of adults will get at least once.10-18% of those with shingles get often debilitating nerve pain called Post-Herpetic Neuralgia (PHN), and 30-50% have PHN lasting >1 year (Kawai, et al. BMJOpen 2014). Contracting shingles raises stroke / major cardiovascular event risk by ~30% (Curhan, et al. J Am Heart Assoc, 2022) and has been linked to dementia / Alzheimer’s Disease (Eyting, et al. medRxiv (preprint), 2023).

[0004] Chickenpox is the highly contagious primary infection from the varicella zoster virus. Higher morbidity in infants and mortality in individuals with an impaired immune system. Chickenpox during pregnancy can cause birth defects or serious newborn infection. Virtually all adults have been exposed to the varicella virus. Among the 1.9 billion people age 50+ worldwide, 278 million cases of shingles and 20.7 million cases of postherpetic neuralgia (PHN) will occur globally over the next decade absent vaccination (Harbecke, et al. J Infect Dis, 2021). SUMMARY

[0005] Varicella zoster virus (VZV) is the cause of varicella (also known as chickenpox and attributable to primary infection) and herpes zoster, also known as shingles and attributable to reactivation from VZV viral latency. Prior to the licensure of Varivax® (Merck) for prevention of primary VZV infection and Zostavax® (Merck) for prevention of herpes zoster, more than 90% of the North American population at least 50 years old had acquired VZV, and approximately one-third of adults would develop HZ over the course of their lifetimes. With the introduction of routine use of live-attenuated varicella vaccine in childhood, complications from VZV have dropped significantly, though notably the incidence of herpes zoster has increased markedly (CDC, 2020).Docket No.: CURV-010 / 02WO 340277-2148

[0006] In 2017, a second herpes zoster vaccine, Shingrix® (GSK), was approved for prevention of herpes zoster in immunocompetent adults and the US Advisory Committee on Immunization Practices recommended this vaccine for adults of age 50, including those who have previously been immunized with Zostavax®. This vaccine utilizes a VZV glycoprotein E (gE) subunit adjuvanted with a combination of a toll-like receptor 4 (TLR4) agonist monophosphoryl lipid A (MPL) and a saponin (QS21) formulated in liposomes.

[0007] Despite the approval of Shingrix in more than 30 countries for the prevention of HZ in adults, the shingles market remains largely underserved, particularly outside the United States. Of the over 800 million adults aged 50 or over, Shingrix® has been administered to less than 3% of eligible adults in Europe (excluding Germany, with an administration rate of about 12%), Canada, Australia, and Japan. Of the 486+ million adults over age 50 in China, only 1.2% have received Shingrix®.

[0008] While immunogenicity in older adults, 50 years of age, is superior to that observed with Zostavax®, reactogenicity to the Shingrix® vaccine is high; approximately one out of six vaccinees develop adverse reactions that interfere with daily activities (grade 3). Furthermore, even in adults who have received the initial dose of Shingrix®, 20-30% of do not go back for the required second dose due to poor tolerance of the vaccine (Patterson, et al. Hum Vaccin Immunother, 2021), increasing the incidence rate of shingles by 45% (Izurieta, et al. Clin Infect Dis, 2021).

[0009] Therefore, there remains a need in the art for shingles vaccines that are effective and well tolerated.

[0010] Amezosvatein is a novel gE subunit vaccine that is adjuvanted with a new- generation TLR4 agonist in an oil-in-water emulsion, SLA-SE. A Phase 2 trial evaluating the safety, tolerability, and immunogenicity of amezosvatein compared to Shingrix in participants 50 years of age and older demonstrated the noninferiority of amezosvatein versus Shingrix in anti-gE GMC at Day 84. The anti-gE GMFR and VRR for amezosvatein were similar to those for Shingrix.

[0011] Importantly, the incidence of Grade 2 solicited local and solicited system adverse events was lower for participants treated with amezosvatein than for those treated with Shingrix, indicating an increase in tolerability of amezosvatein as compared to Shingrix. In a nationwide (USA) survey of primary care physicians, patients who refused Shingrix vaccination reported fear of side effects was ‘often / always’ (15%) or ‘sometimes’ (54%) the cause (Hurley, et al. J Gen Intern Med, 2022). Furthermore, in a survey of Americans age 50+, 48% of respondents avoided Shingrix vaccination due to tolerability concerns (Wagner, et al.2024. Submitted for publication) 39% of people who received only one dose of Shingrix pointed to tolerability concerns impacting their decision to not get a second dose (Wagner, et al.2024. Submitted for publication).Docket No.: CURV-010 / 02WO 340277-2148

[0012] In some embodiments, the present disclosure provides a lyophilized composition comprising: about 110 mcg to about 130 mcg of a Varicella-zoster virus gE glycoprotein (VZV-gE) antigen comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 2; an SLA-SE adjuvant, and one or more excipients selected from sodium chloride (NaCl), disodium hydrogen phosphate dihydrate (Na2HPO4· 2H2O), potassium dihydrogen phosphate (KH2PO4), sucrose, and L-Arginine monohydrochloride.

[0013] In some embodiments, the lyophilized composition comprises each of NaCl, Na2HPO4· 2H2O, KH2PO4, sucrose, and L-Arginine monohydrochloride.

[0014] In some embodiments, the lyophilized composition comprises about 3 mg to about 4 mg of NaCl. In some embodiments, the lyophilized composition comprises about 3.6 mg NaCl. In some embodiments, the lyophilized composition comprises about 0.3 mg to about 0.5 mg Na2HPO4· 2H2O. In some embodiments, the lyophilized composition comprises about 0.4 mg Na2HPO4· 2H2O. In some embodiments, the lyophilized composition comprises about 0.04 mg to about 0.07 mg KH2PO4. In some embodiments, the lyophilized composition comprises about 0.058 mg KH2PO4. In some embodiments, the lyophilized composition comprises about 35 mg to about 45 mg sucrose. In some embodiments, the lyophilized composition comprises about 40 mg sucrose. In some embodiments, the lyophilized composition comprises about 5 mg to about 7 mg L- Arginine monohydrochloride. In some embodiments, the lyophilized composition comprises about 6 mg L-Arginine monohydrochloride. In some embodiments, the lyophilized composition comprises about 120 mcg of the VZV-gE antigen.

[0015] In some embodiments, the present disclosure provides a lyophilized composition comprising: about 110 mcg to about 130 mcg of a Varicella-zoster virus gE glycoprotein (VZV-gE) antigen comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 2; about 3 mg to about 4 mg of NaCl; about 0.3 mg to about 0.5 mg Na2HPO4· 2H2O; about 0.04 to about 0.07 mg KH2PO4; about 35 mg to about 45 mg sucrose; and about 5 mg to about 7 mg L-Arginine monohydrochloride.

[0016] In some embodiments, the lyophilized composition comprises about 120 mcg of the VZV-gE antigen; about 3.6 mg NaCl; about 0.4 mg Na2HPO4· 2H2O; about 0.058 mg KH2PO4; about 40 mg sucrose; and about 6 mg L-Arginine monohydrochloride.

[0017] In some embodiments, the present disclosure provides an emulsion composition comprising: about 15 mcg / mL to about 20 mcg / mL of an SLA adjuvant; an oil; and one or more excipients selected from 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC), poloxamer 188, Vitamin E, glycerol, and ammonium phosphate.

[0018] In some embodiments, the oil is squalene and the emulsion composition comprises about 25 mg / mL to about 35 mg / mL squalene. In some embodiments, the emulsion composition comprises about 30.6 mg / mL squalene. In some embodiments, theDocket No.: CURV-010 / 02WO 340277-2148 oil is squalene and the emulsion composition comprises about 35 mg / mL to about 45 mg / mL. In some embodiments, the emulsion composition comprises about 39.11 mg / mL squalene.

[0019] In some embodiments, the emulsion composition comprises about 5 mg / mL to about 8 mg / mL DMPC. In some embodiments, the emulsion composition comprises about 6.84 mg / mL DMPC. In some embodiments, the emulsion composition comprises about 5 mg / mL to about 9 mg / mL DMPC. In some embodiments, the emulsion composition comprises about 8.74 mg / mL DMPC.

[0020] In some embodiments, the emulsion composition comprises about 200 mcg / mL to about 400 mcg / mL poloxamer 188. In some embodiments, the emulsion composition comprises about 320 mcg / mL poloxamer 188. In some embodiments, the emulsion composition comprises about 200 mcg / mL to about 450 mcg / mL poloxamer 188. In some embodiments, the emulsion composition comprises about 410 mcg / mL poloxamer 188.

[0021] In some embodiments, the emulsion composition comprises about 50 mcg / mL to about 200 mcg / mL Vitamin E. In some embodiments, the emulsion composition comprises about 180 mcg / mL Vitamin E. In some embodiments, the emulsion composition comprises about 50 mcg / mL to about 250 mcg / mL Vitamin E. In some embodiments, the emulsion composition comprises about 230 mcg / mL Vitamin E.

[0022] In some embodiments, the emulsion composition comprises about 15 mg / mL to about 25 mg / mL glycerol. In some embodiments, the emulsion composition comprises about 20.7 mg / mL glycerol. In some embodiments, the emulsion composition comprises about 15 mg / mL to about 30 mg / mL glycerol. In some embodiments, the emulsion composition comprises about 26.46 mg / mL glycerol.

[0023] In some embodiments, the ammonium phosphate comprises ammonium phosphate, monobasic and ammonium phosphate, dibasic. In some embodiments, the emulsion composition comprises about 1.5 mg / mL to about 3.5 mg / mL of ammonium phosphate, monobasic and about 0.05 mg / mL to about 2.5 mg / mL ammonium phosphate, dibasic. In some embodiments, the emulsion composition comprises about 2.43 mg / mL ammonium phosphate, monobasic and about 0.15 mg / mL ammonium phosphate, dibasic. In some embodiments, the emulsion composition comprises about 3.11 mg / mL ammonium phosphate, monobasic and about 0.2 mg / mL ammonium phosphate, dibasic.

[0024] In some embodiments, the emulsion composition comprises 18 mcg / mL of an SLA adjuvant; 30.6 mg / mL squalene; 6.84 mg / mL DMPC; 320 mcg / mL poloxamer 188; 180 mcg / mL Vitamin E; 20.7 mg / mL glycerol; 2.43 mg / mL ammonium phosphate, monobasic; and 150 mcg / mL ammonium phosphate, dibasic.

[0025] In some embodiments, the emulsion composition comprises 23 mcg / mL of an SLA adjuvant; 39.11 mg / mL squalene; 8.74 mg / mL DMPC; 410 mcg / mL poloxamer 188; 230Docket No.: CURV-010 / 02WO 340277-2148 mcg / mL Vitamin E; 26.46 mg / mL glycerol; 3.11 mg / mL ammonium phosphate, monobasic; and 200 mcg / mL ammonium phosphate, dibasic.

[0026] In some embodiments, the present disclosure provides an immunogenic composition comprising: about 110 mcg / mL to about 120 mcg / mL of a Varicella-zoster virus gE glycoprotein (VZV-gE) antigen comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 2; about 15 mcg / mL to about 25 mcg / mL of an SLA adjuvant; an oil; one or more excipients selected from sodium chloride (NaCl), disodium hydrogen phosphate dihydrate (Na2HPO4· 2H2O), potassium dihydrogen phosphate (KH2PO4), sucrose, and L-Arginine monohydrochloride; and one or more excipients selected from 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC), poloxamer 188, Vitamin E, glycerol, and ammonium phosphate.

[0027] In some embodiments, the immunogenic composition comprises each of NaCl, Na2HPO4· 2H2O, KH2PO4, sucrose, L-Arginine monohydrochloride, DMPC, poloxamer 188, Vitamin E, glycerol, and ammonium phosphate. In some embodiments, the immunogenic composition comprises about 25 mg / mL to about 40 mg / mL squalene. In some embodiments, the immunogenic composition comprises about 29.4 mg / mL squalene. In some embodiments, the immunogenic composition comprises about 37.6 mg / mL squalene. In some embodiments, the immunogenic composition comprises about 115 mcg / mL of a VZV gE antigen.

[0028] In some embodiments, the immunogenic composition comprises about 3 mg to about 4 mg of NaCl; about 0.3 mg to about 0.5 mg Na2HPO4· 2H2O; about 0.04 mg to about 0.07 mg KH2PO4; 35 mg to about 45 mg sucrose; about 5 mg to about 7 mg L- Arginine monohydrochloride; about 5 mg / mL to about 8 mg / mL DMPC; about 200 mcg mcg / mL to about 400 mcg / mL poloxamer 188; about 50 mcg / mL to about 200 mcg / mL Vitamin E; about 15 mg / mL to about 25 mg / mL glycerol; about 1.5 mg / mL to about 3.5 mg / mL of ammonium phosphate, monobasic; and about 0.05 mg / mL to about 2.5 mg / mL ammonium phosphate, dibasic.

[0029] In some embodiments, the immunogenic composition comprises about 3 mg to about 4 mg of NaCl; about 0.3 mg to about 0.5 mg Na2HPO4· 2H2O; about 0.04 mg to about 0.07 mg KH2PO4; 35 mg to about 45 mg sucrose; about 5 mg to about 7 mg L- Arginine monohydrochloride; about 5 mg / mL to about 9 mg / mL DMPC; about 200 mcg mcg / mL to about 450 mcg / mL poloxamer 188; about 50 mcg / mL to about 250 mcg / mL Vitamin E; about 15 mg / mL to about 30 mg / mL glycerol; about 1.5 mg / mL to about 3.5 mg / mL of ammonium phosphate, monobasic; and about 0.05 mg / mL to about 2.5 mg / mL ammonium phosphate, dibasic.

[0030] In some embodiments, the immunogenic composition comprises about 3.46 mg / mL of NaCl; about 0.385 mg / mL Na2HPO4· 2H2O; about 0.056 mg / mL KH2PO4; aboutDocket No.: CURV-010 / 02WO 340277-2148 38.5 mg / mL sucrose; about 5.77 mg / mL L-Arginine monohydrochloride; about 6.58 mg / mL DMPC; about 0.31 mg / mL poloxamer 188; about 173 mcg / mL Vitamin E; about 19.9 mg / mL glycerol; about 2.34 mg / mL ammonium phosphate, monobasic; and about 0.144 mg / mL ammonium phosphate, dibasic.

[0031] In some embodiments, the immunogenic composition comprises about 3.46 mg / mL of NaCl; about 0.385 mg / mL Na2HPO42H2O; about 0.056 mg / mL KH2PO4; about 38.5 mg / mL sucrose; about 5.77 mg / mL L-Arginine monohydrochloride; about 8.40 mg / mL DMPC; about 0.39 mg / mL poloxamer 188; about 221 mcg / mL Vitamin E; about 25.4 mg / mL glycerol; about 2.99 mg / mL ammonium phosphate, monobasic; and about 0.192 mg / mL ammonium phosphate, dibasic.

[0032] In some embodiments, the present disclosure provides a dose of an immunogenic composition comprising: about 100, 101, 102, 103, or 104 mcg of a Varicella-zoster virus gE glycoprotein (VZV-gE) antigen comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 2; about 15 mcg of an SLA adjuvant; about 26.5 mg of squalene; about 3.12 mg of NaCl; about 0.346 mg Na2HPO4· 2H2O; about 0.050 mg KH2PO4; about 34.6 mg sucrose; about 5.19 mg L-Arginine monohydrochloride; about 5.92 mg DMPC; about 0.277 mg poloxamer 188; about 156 mcg Vitamin E; about 17.9 mg glycerol; about 2.1 mg ammonium phosphate, monobasic; and about 0.13 mg ammonium phosphate, dibasic.

[0033] In some embodiments, the present disclosure provides a dose of an immunogenic composition comprising: about 100, 101, 102, 103, or 104 mcg of a Varicella-zoster virus gE glycoprotein (VZV-gE) antigen consisting of the amino acid sequence of SEQ ID NO: 2; about 15 mcg of an SLA adjuvant; about 26.5 mg of squalene; about 3.12 mg of NaCl; about 0.346 mg Na2HPO4· 2H2O; about 0.050 mg KH2PO4; about 34.6 mg sucrose; about 5.19 mg L-Arginine monohydrochloride; about 5.92 mg DMPC; about 0.277 mg poloxamer 188; about 156 mcg Vitamin E; about 17.9 mg glycerol; about 2.1 mg ammonium phosphate, monobasic; and about 0.13 mg ammonium phosphate, dibasic..

[0034] In some embodiments, the present disclosure provides a dose of an immunogenic composition comprising: about 100, 101, 102, 103, or 104 mcg of a Varicella-zoster virus gE glycoprotein (VZV-gE) antigen comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 2; about 20 mcg of an SLA adjuvant; about 33.8 mg of squalene; about 3.12 mg of NaCl; about 0.346 mg Na2HPO4· 2H2O; about 0.050 mg KH2PO4; about 34.6 mg sucrose; about 5.19 mg L-Arginine monohydrochloride; about 7.56 mg DMPC; about 0.355 mg poloxamer 188; about 199 mcg Vitamin E; about 22.9 mg glycerol; about 2.69 mg ammonium phosphate, monobasic; and about 0.17 mg ammonium phosphate, dibasic.Docket No.: CURV-010 / 02WO 340277-2148

[0035] In some embodiments, the present disclosure provides a dose of an immunogenic composition comprising: about 100, 101, 102, 103, or 104 mcg of a Varicella-zoster virus gE glycoprotein (VZV-gE) antigen consisting of the amino acid sequence of SEQ ID NO: 2; about 20 mcg of an SLA adjuvant; about 33.8 mg of squalene; about 3.12 mg of NaCl; about 0.346 mg Na2HPO4· 2H2O; about 0.050 mg KH2PO4; about 34.6 mg sucrose; about 5.19 mg L-Arginine monohydrochloride; about 7.56 mg DMPC; about 0.355 mg poloxamer 188; about 199 mcg Vitamin E; about 22.9 mg glycerol; about 2.69 mg ammonium phosphate, monobasic; and about 0.17 mg ammonium phosphate, dibasic.

[0036] In some embodiments, the present disclosure provides a pre-filled syringe comprising a dose of an immunogenic composition described herein. In some embodiments, the present disclosure provides a method of preventing Herpes Zoster in a subject in need thereof, comprising administration of a dose of an immunogenic composition described herein.

[0037] In some embodiments, the method further comprises administration of a second dose of an immunogenic composition described herein. In some embodiments, the first and second doses are administered at least 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, or 8 weeks apart. In some embodiments, the subject has not previously received a dose of Shingrix®. In some embodiments, the subject has previously received one or more doses of Shingrix®. In some embodiments, the administration is subcutaneous or intramuscular.

[0038] In some aspects disclosed herein is a stock solution comprising a second- generation lipid adjuvant (SLA), 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC), vitamin E, squalene, glycerol, poloxamer 188, ammonium phosphate, monobasic, and / or ammonium phosphate, dibasic; wherein the SLA comprises the structure set forth in formula I or formula IIDocket No.: CURV-010 / 02WO 340277-2148some embodiments, the stock solution comprises: about 100 to about 200 mcg / mL SLA; about 25 to about 75 mg / mL DMPC; about 0.5 to 2.5 mg / mL vitamin E; about 150 to 300 mg / mL squalene; about 150 to 250 mg / mL glycerol; about 1.5 to 3.5 mg / mL poloxamer 188; about 15 to 25 mg / mL ammonium phosphate, monobasic; and / or about 0.5 to 2.5 mg / mL ammonium phosphate, dibasic. In some embodiments, the stock solution comprises: 150 mcg / mL SLA; 57 mg / mL DMPC; 1.5 mg / mL vitamin E; 255 mg / mL squalene; 172.5 mg / mL glycerol; 2.7 mg / mL poloxamer 188; 20.25 mg / mL ammonium phosphate, monobasic; and 1.275 mg / mL ammonium phosphate, dibasic. BRIEF DESCRIPTION OF DRAWINGS

[0039] FIG.1 provides the magnitude of the humoral response for amezosvatein and Shingrix® treatment groups.

[0040] FIG.2A – FIG.2B provide secondary immunogenicity endpoint results. FIG.2A provides the immune response fold-increase from baseline. FIG.2B provides the vaccine response rate.

[0041] FIG.3 shows anti-gE GMC ELISA values (y-axis) by age (x-axis).

[0042] FIG.4 provides a summary of incidences of solicited adverse events.

[0043] FIG.5 provides a summary of systemic adverse events.

[0044] FIG.6 provides a summary of local adverse events.

[0045] FIG.7 provides a summary of selected adverse events. DETAILED DESCRIPTION

[0046] Unless defined otherwise, all technical and scientific terms used herein have the meaning commonly understood by one of ordinary skill in the art to which the invention pertains. Specific terminology of particular importance to the description of the present invention is defined below. In this specification and the appended claims, the singularDocket No.: CURV-010 / 02WO 340277-2148 forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, “a polypeptide” refers not only to a single polypeptide but also to a combination of two or more different polypeptides that may or may not be combined, “an adjuvant” refers to a single adjuvant as well as to two or more adjuvants that may be separate or combined in a single composition, and the like.

[0047] The term “about,” when immediately preceding a numerical value, means a range (e.g., plus or minus 5% of that value). For example, “about 50” can mean 47.5 to 52.5, “about 25,000” can mean 23,750 to 26,250, etc., unless the context of the disclosure indicates otherwise, or is inconsistent with such an interpretation.

[0048] The present disclosure provides compositions comprising a VZV gE antigen and / or an adjuvant and one or more excipients. The excipients are immunologically and pharmacologically inert components that are “pharmaceutically acceptable.” A “pharmaceutically acceptable” component herein is one that (1) can be included in a immunogenic composition administered to a subject without causing significant unwanted biological effects or interacting in a deleterious manner with any of the other components of the formulation; and (2) meets the criteria set out in the Inactive Ingredient prepared by the U.S. Food and Drug Administration, and, preferably, has also been designated “Generally Regarded as Safe” (“GRAS”). In some embodiments, excipients include stabilizers, tonicity agents, antioxidants, and / or a buffer. They are generally safe for administering to humans according to established governmental standards.

[0049] Exemplary stabilizers include sucrose, L-Arginine monohydrochloride, and poloxamer 188. Exemplary tonicity agents include sodium chloride (NaCl) and glycerol. Exemplary buffers include potassium phosphate (e.g., potassium dihydrogen phosphate), disodium hydrogen phosphate dihydrate, and ammonium phosphate (e.g., ammonium phosphate, monobasic and ammonium phosphate, dibasic). Exemplary antioxidants include vitamin E. VZV antigens

[0050] As used herein, the term “antigen” refers to a substance such as a polypeptide or peptide that is capable of eliciting an immune response. The immunogenic compositions described herein comprise the gE antigen of SEQ ID NO: 1, wherein the signal peptide has been cleaved from the antigen polypeptide sequence. The signal peptide sequence of SEQ ID NO: 1 is shown in bold and underlined text in Table 1. In particular embodiments, the immunogenic compositions described herein comprise the gE antigen of SEQ ID NO: 2. In some embodiments, the compositions described herein comprise a VZV gE antigen that is at least 95% identical to SEQ ID NO: 2 or 2. In particularDocket No.: CURV-010 / 02WO 340277-2148 embodiments, the VZV gE antigen comprises or consists of the gE antigen of SEQ ID NO: 2. Table 1: Exemplary VZV gE AntigensAdjuvants

[0051] In some embodiments, the compositions comprise one or more adjuvants. As used herein, the term “adjuvant” refers to a compound that, when used in combination with an antigen, augments the immune response to one or more antigens in the immunogenic composition. Augmentation of the immune response may include increasing the antibody titers raised against the one or more antigens, increasing the clonality of the antibody response against the one or more antigens, increasing the intensity of the cellular immune response (e.g.¸ increased memory T cell formation, increased acute cytokine production), and / or diversification of the cellular immune response (e.g., increasing the number of different types of cytokines produced, increasing proliferation of one or more T cell phenotypes, etc.).

[0052] In some embodiments, the adjuvant is a second-generation lipid adjuvant (SLA). In particular, SLA is a synthetic hexa-acylated lipid. See U.S.10,632,191; U.S.9,480,740; U.S. 9,814,772; U.S. 8,722,064; and U.S. 10,940,198, each incorporated herein by reference. Herein, compositions comprising SLA can be provided as a squalene oil-in- water emulsion formulation (SLA-SE).Docket No.: CURV-010 / 02WO 340277-2148

[0053] In some embodiments, the adjuvant is SLA and has the following structure:(Formula I)

[0054] or a pharmaceutically acceptable salt thereof.

[0055] The SLA adjuvant can generally be utilized as the free base or free acid. Alternatively, the SLA adjuvant can may be used in the form of an acid or base addition salt. Acid addition salts of the free amino compounds of SLA may be prepared by methods well known in the art, and may be formed from organic and inorganic acids. Suitable organic acids include maleic, fumaric, benzoic, ascorbic, succinic, methanesulfonic, acetic, oxalic, propionic, tartaric, salicylic, citric, gluconic, lactic, mandelic, cinnamic, aspartic, stearic, palmitic, glycolic, glutamic, and benzenesulfonic acids. Suitable inorganic acids include hydrochloric, hydrobromic, sulfuric, phosphoric, and nitric acids.

[0056] Similarly, base addition salts of the acid compounds of SLA may be prepared by methods well known in the art, and may be formed from organic and inorganic bases. Suitable organic bases include, but are not limited to, triethylamine and pyridine. Suitable inorganic bases include, but are not limited to, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, and ammonia. Thus, the term “pharmaceutically acceptable salt” of Formula (I) is intended to encompass any and all acceptable salt forms. In some embodiments, the inorganic base addition is ammonia.Docket No.: CURV-010 / 02WO 340277-2148

[0057] In some embodiments, the SLA adjuvant of Formula (I) is a pharmaceutically acceptable salt. In some embodiments, the SLA adjuvant of Formula (I) is an ammonium salt. In some embodiments, the SLA adjuvant of Formula (I) is a pharmaceutically acceptable salt having a representative structure:Lyophilized Compositions

[0058] In some embodiments, the present disclosure provides lyophilized compositions comprising about 110 mcg to about 130 mcg of a Varicella-zoster virus gE glycoprotein (VZV-gE) antigen comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 2; and one or more excipients selected from sodium chloride (NaCl), disodium hydrogen phosphate dihydrate (Na2HPO4· 2H2O), potassium dihydrogen phosphate (KH2PO4), sucrose, and L-Arginine monohydrochloride.

[0059] In some embodiments, the lyophilized composition comprises about 110 mcg to about 130 mcg of a Varicella-zoster virus gE glycoprotein (VZV-gE) antigen comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 2. In some embodiments, the VZV-gE antigen consists of the amino acid sequence of SEQ ID NO: 2. In some embodiments, the lyophilized composition comprises about 115 mcg to about 130 mcg, between about 120 mcg to about 130 mcg, between about 125 mcg to about 130 mcg, between about 110 mcg to about 125 mcg, between about 115 mcg to about 125 mcg, between about 120 mcg to about 125 mcg, between about 110 mcg to aboutDocket No.: CURV-010 / 02WO 340277-2148 120 mcg, or between about 115 mcg to about 120 mcg of the VZV-gE antigen. In some embodiments, the lyophilized composition comprises about 110 mcg, about 111 mcg, about 112 mcg, about 113 mcg, about 114 mcg, about 115 mcg, about 116 mcg, about 117 mcg, about 118 mcg, about 119 mcg, about 120 mcg, about 121 mcg, about 122 mcg, about 123 mcg, about 124 mcg, about 125 mcg, about 126 mcg, about 127 mcg, about 128 mcg, about 129 mcg, or about 130 mcg of the VZV-gE antigen. In some embodiments, the lyophilized composition comprises about 120 mcg of the VZV-gE antigen. In some embodiments, the lyophilized composition comprises 110 mcg, 111 mcg, 112 mcg, 113 mcg, 114 mcg, 115 mcg, 116 mcg, 117 mcg, 118 mcg, 119 mcg, 120 mcg, 121 mcg, 122 mcg, 123 mcg, 124 mcg, 125 mcg, 126 mcg, 127 mcg, 128 mcg, 129 mcg, or 130 mcg of the VZV-gE antigen. In some embodiments, the lyophilized composition comprises 120 mcg of the VZV-gE antigen.

[0060] In some embodiments, the lyophilized composition comprises a VZV-gE antigen and NaCl. In some embodiments, the lyophilized composition comprises about 2mg to about 5mg NaCl. In some embodiments, the lyophilized composition comprises between about 2.5 mg to about 5 mg, about 3 mg to about 5 mg, about 3.5 mg to about 5 mg, about 4 mg to about 5 mg, about 4.5 mg to about 5 mg, about 2 mg to about 4.5 mg, about 2.5 mg to about 4.5 mg, about 3 mg to about 4.5 mg, about 3.5 mg to about 4.5 mg, about 4 mg to about 4.5 mg, about 2 mg to about 4 mg, about 2.5 mg to about 4 mg, about 3 mg to about 4 mg, about 3.5 mg to about 4 mg, about 2 mg to about 3.5 mg, about 2.5 mg to about 3.5 mg, about 3 mg to about 3.5 mg, about 2 mg to about 3 mg, about 2.5 mg to about 3 mg, or about 2 mg to about 2.5 mg NaCl. In some embodiments, the lyophilized composition comprises about 2 mg, about 2.5 mg, about 3 mg, about 3.5 mg, about 4 mg, about 4.5 mg, about 5 mg, about 5.5 mg, or about 6 mg NaCl. In some embodiments, the lyophilized composition comprises 3 mg, 3.1 mg, 3.2 mg, 3.3 mg, 3.4 mg, 3.5 mg, 3.6 mg, 3.7 mg, 3.8 mg, 3.9 mg, or 4 mg. In some embodiments, the lyophilized composition comprises 3.6 mg NaCl.

[0061] In some embodiments, the lyophilized composition comprises a VZV-gE antigen and Na2HPO4· 2H2O. In some embodiments, the lyophilized composition comprises about 300 mcg to about 500 mcg Na2HPO4· 2H2O. In some embodiments, the lyophilized composition comprises about 300 mcg to about 450 mcg, about 300 mcg to about 400 mcg, about 300 mcg to about 350 mcg, about 350 mcg to about 500 mcg, about 350 mcg to about 450 mcg, about 350 mcg to about 400 mcg, about 400 mcg to about 500 mcg, about 400 mcg to about 450 mcg, or about 450 mcg to about 500 mcg Na2HPO4 · 2H2O. In some embodiments, the lyophilized composition comprises about 300 mcg, about 325 mcg, about 350 mcg, about 375 mcg, about 400 mcg, about 425 mcg, about 450 mcg, about 475 mcg, or about 500 mcg Na2HPO4· 2H2O. In some embodiments, theDocket No.: CURV-010 / 02WO 340277-2148 lyophilized composition comprises 350 mcg, 360 mcg, 370 mcg, 380 mcg, 390 mcg, 400 mcg, 410 mcg, 420 mcg, 430 mcg, 440 mcg, or 450 mcg Na2HPO4· 2H2O. In some embodiments, the lyophilized composition comprises a VZV-gE antigen and 400 mcg Na2HPO4· 2H2O.

[0062] In some embodiments, the lyophilized composition comprises a VZV-gE antigen and KH2PO4. In some embodiments, the lyophilized composition comprises about 40 mcg to about 70 mcg. In some embodiments, the lyophilized composition comprises about 40 mcg to about 65 mcg, about 40 mcg to about 60 mcg, about 40 mcg to about 55 mcg, about 40 mcg to about 50 mcg, about 40 mcg to about 45 mcg, about 45 mcg to about 70 mcg, about 45 mcg to about 65 mcg, about 45 mcg to about 60 mcg, about 45 mcg to about 55 mcg, about 45 mcg to about 50 mcg, about 50 mcg to about 70 mcg, about 50 mcg to about 65 mcg, about 50 mcg to about 60 mcg, about 50 mcg to about 55 mcg, about 55 mcg to about 70 mcg, about 55 mcg to about 65 mcg, about 55 mcg to about 60 mcg, about 60 mcg to about 70 mcg, about 60 mcg to about 65 mcg, or about 65 mcg to about 70 mcg KH2PO4. In some embodiments, the lyophilized composition comprises about 40 mcg, about 45 mcg, about 50 mcg, about 55 mcg, about 60 mcg, about 65 mcg, or about 70 mcg KH2PO4. In some embodiments, the lyophilized composition comprises 50 mcg, 51 mcg, 52 mcg, 53 mcg, 54 mcg, 55 mcg, 56 mcg, 57 mcg, 58 mcg, 59 mcg, 60 mcg KH2PO4. In some embodiments, the lyophilized composition comprises a VZV-gE antigen and 58 mcg KH2PO4.

[0063] In some embodiments, the lyophilized composition comprises a VZV-gE antigen and sucrose. In some embodiments, the lyophilized composition comprises about 30 mg and about 50 mg sucrose. In some embodiments, the lyophilized composition comprises about 30 mg to about 45 mg, about 30 mg to about 40 mg, about 30 mg to about 35 mg, about 35 mg to about 50 mg, about 35 mg to about 45 mg, about 35 mg to about 40 mg, about 40 mg to about 50 mg, about 40 mg to about 45 mg, about 45 mg to about 50 mg sucrose. In some embodiments, the lyophilized composition comprises about 30 mg, about 35 mg, about 40 mg, about 45 mg, or about 50 mg sucrose. In some embodiments, the lyophilized composition comprises 35 mg, 36 mg, 37 mg, 38 mg, 39 mg, 40 mg, 41 mg, 42 mg, 43 mg, 44 mg, or 45 mg sucrose. In some embodiments, the lyophilized composition comprises 40 mg sucrose.

[0064] In some embodiments, the lyophilized composition comprises a VZV-gE antigen and L-Arginine monohydrochloride. In some embodiments, the lyophilized composition comprises about 4 mg to about 8 mg L-Arginine monohydrochloride. In some embodiments, the lyophilized composition comprises about 4 mg to about 7.5 mg, about 4 mg to about 7 mg, about 4 mg to about 6.5 mg, about 4 mg to about 6 mg, about 4 mg to about 5.5 mg, about 4 mg to about 5 mg, about 4 mg to about 4.5 mg, about 4.5 mg toDocket No.: CURV-010 / 02WO 340277-2148 about 8 mg, about 4.5 mg to about 7.5 mg, about 4.5 mg to about 7 mg, about 4.5 mg to about 6.5 mg, about 4.5 mg to about 6 mg, about 4.5 mg to about 5.5 mg, about 4.5 mg to about 5 mg, about 5 mg to about 8 mg, about 5 mg to about 7.5 mg, about 5 mg to about 7 mg, about 5 mg to about 6.5 mg, about 5 mg to about 6 mg, about 5 mg to about 5.5 mg, about 5.5 mg to about 8 mg, about 5.5 mg to about 7.5 mg, about 5.5 mg to about 7 mg, about 5.5 mg to about 6 mg, about 6 mg to about 8 mg, about 6 mg to about 7.5 mg, about 6 mg to about 7 mg, about 6 mg to about 6.5 mg, about 6.5 mg to about 8 mg, about 6.5 mg to about 7.5 mg, about 6.5 mg to about 7 mg, about 7 mg to about 8 mg, about 7 mg to about 7.5 mg, or about 7.5 mg to about 8 mg L-Arginine monohydrochloride. In some embodiments, the lyophilized composition comprises 4 mg, 4.5 mg, 5 mg, 5.5 mg, 6 mg, 6.5 mg, 7 mg, 7.5 mg, or 8 mg L-Arginine monohydrochloride. In some embodiments, the lyophilized composition comprises 6 mg L-Arginine monohydrochloride.

[0065] In some embodiments, the lyophilized composition comprises: (a) about 110 mcg to about 130 mcg of a Varicella-zoster virus gE glycoprotein (VZV-gE) antigen comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 2; (b) about 3 mg to about 4 mg of NaCl; (c) about 0.3 mg to about 0.5 mg Na2HPO4· 2H2O; (d) about 0.04 to about 0.07 mg KH2PO4; (e) about 35 mg to about 45 mg sucrose; and (f) about 5 mg to about 7 mg L-Arginine monohydrochloride.

[0066] In some embodiments, the lyophilized composition comprises: (a) about 120 mcg of the VZV-gE antigen; (b) about 3.6 mg NaCl; (c) about 0.4 mg Na2HPO4· 2H2O; (d) about 0.058 mg KH2PO4; (e) about 40 mg sucrose; and (f) about 6 mg L-Arginine monohydrochloride.Docket No.: CURV-010 / 02WO 340277-2148 Emulsion Compositions

[0067] In some embodiments, the present disclosure comprises an emulsion comprising an SLA adjuvant of Formula (I) or a pharmaceutically acceptable salt thereof; an oil; and one or more excipients selected from 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC), poloxamer 188, Vitamin E, glycerol, and ammonium phosphate.

[0068] In some embodiments, the emulsion comprises about 15 mcg / mL to about 20 mcg / mL of the SLA adjuvant of Formula (I) or a pharmaceutically acceptable salt thereof. In some embodiments, the emulsion comprises about 15 mcg to about 19 mcg, about 15 mcg / mL to about 18 mcg / mL, about 15 mcg / mL to about 17 mcg / mL, about 15 mcg / mL to about 16 mcg / mL, about 16 mcg / mL to about 20 mcg / mL, about 16 mcg / mL to about 19 mcg / mL, about 16 mcg / mL to about 18 mcg / mL, about 16 mcg / mL to about 17 mcg / mL, about 17 mcg / mL to about 20 mcg / mL, about 17 mcg / mL to about 19 mcg / mL, about 17 mcg / mL to about 18 mcg / mL, about 18 mcg / mL to about 20 mcg / mL, about 18 mcg / mL to about 19 mcg / mL, or about 19 mcg / mL to about 20 mcg / mL of the SLA adjuvant. In some embodiments, the emulsion comprises about 15 mcg / mL, about 16 mcg / mL, about 17 mcg / mL, about 18 mcg / mL, about 19 mcg / mL, or about 20 mcg / mL of the SLA adjuvant. In some embodiments, the emulsion comprises about 17.5 mcg / mL, about 17.6 mcg / mL, about 17.7 mcg / mL, about 17.8 mcg / mL, about 17.9 mcg / mL, about 18.0 mcg / mL, about 18.1 mcg / mL, about 18.2 mcg / mL, about 18.3 mcg / mL, about 18.4 mcg / mL, or about 18.5 mcg / mL of the SLA adjuvant. In some embodiments, the emulsion comprises 17.5 mcg / mL, 17.6 mcg / mL, 17.7 mcg / mL, 17.8 mcg / mL, 17.9 mcg / mL, 18.0 mcg / mL, 18.1 mcg / mL, 18.2 mcg / mL, 18.3 mcg / mL, 18.4 mcg / mL, or 18.5 mcg / mL of the SLA adjuvant. In some embodiments, the emulsion comprises 18 mcg / mL of the SLA adjuvant.

[0069] In some embodiments, the emulsion comprises about 15 mcg / mL to about 25 mcg / mL of the SLA adjuvant of Formula (I) or a pharmaceutically acceptable salt thereof. In some embodiments, the emulsion comprises 19 mcg / mL of the SLA adjuvant, 19.5 mcg / mL of the SLA adjuvant, 20 mcg / mL of the SLA adjuvant, 20.5 mcg / mL of the SLA adjuvant, 21 mcg / mL of the SLA adjuvant, 21.5 mcg / mL of the SLA adjuvant, 22 mcg / mL of the SLA adjuvant, 22.5 mcg / mL of the SLA adjuvant, 23 mcg / mL of the SLA adjuvant, 23.5 mcg / mL of the SLA adjuvant, 24 mcg / mL of the SLA adjuvant, 24.5 mcg / mL of the SLA adjuvant, or 25 mcg / mL of the SLA adjuvant. In some embodiments, the emulsion comprises about 22.5 mcg / mL, about 22.6 mcg / mL, about 22.7 mcg / mL, about 22.8 mcg / mL, about 22.9 mcg / mL, about 23.0 mcg / mL, about 23.1 mcg / mL, about 23.2 mcg / mL, about 23.3 mcg / mL, about 23.4 mcg / mL, or about 23.5 mcg / mL of the SLA adjuvant. In some embodiments, the emulsion comprises 22.5 mcg / mL, 22.6 mcg / mL, 22.7 mcg / mL, 22.8 mcg / mL, 22.9 mcg / mL, 23.0 mcg / mL, 23.1 mcg / mL, 23.2 mcg / mL,Docket No.: CURV-010 / 02WO 340277-2148 23.3 mcg / mL, 23.4 mcg / mL, or 23.5 mcg / mL of the SLA adjuvant. In some embodiments, the emulsion comprises 23 mcg / mL of the SLA adjuvant.

[0070] In some embodiments, the emulsion comprises the SLA adjuvant and squalene. In some embodiments, the emulsion comprises about 20 mg / mL to about 40 mg / mL squalene. In some embodiments, the emulsion comprises about 20 mg / mL to about 35 mg / mL, about 20 mg / mL to about 30 mg / mL, about 20 mg / mL to about 35 mg / mL, about 25 mg / mL to about 40 mg / mL, about 25 mg / mL to about 35 mg / mL, about 25 mg / mL to about 30 mg / mL, about 30 mg / mL to about 40 mg / mL, about 30 mg / mL to about 35 mg / mL, or about 35 mg / mL to about 40 mg / mL squalene. In some embodiments, the emulsion comprises about 20 mg / mL, about 25 mg / mL, about 30 mg / mL, about 35 mg / mL, or about 40 mg / mL squalene. In some embodiments, the emulsion comprises about 25 mg / mL, about 26 mg / mL, about 27 mg / mL, about 28 mg / mL, about 29 mg / mL, about 30 mg / mL, about 31 mg / mL, about 32 mg / mL, about 33 mg / mL, about 34 mg / mL, or about 35 mg / mL squalene. In some embodiments, the emulsion comprises about 30.1 mg / mL, about 30.2 mg / mL, about 30.3 mg / mL, about 30.4 mg / mL, about 30.5 mg / mL, about 30.6 mg / mL, about 30.7 mg / mL, about 30.8 mg / mL, or about 30.9 mg / mL squalene. In some embodiments, the emulsion comprises 30.1 mg / mL, 30.2 mg / mL, 30.3 mg / mL, 30.4 mg / mL, 30.5 mg / mL, 30.6 mg / mL, 30.7 mg / mL, 30.8 mg / mL, or 30.9 mg / mL squalene. In some embodiments, the emulsion comprises 30.6 mg / mL squalene.

[0071] In some embodiments, the emulsion comprises the SLA adjuvant and squalene. In some embodiments, the emulsion comprises about 36 mg / mL squalene, about 37 mg / mL squalene, about 38 mg / mL squalene, about 39 mg / mL squalene, or about 40 mg / mL squalene. In some embodiments, the emulsion comprises about 38.5 mg / mL, about 38.6 mg / mL, about 38.7 mg / mL, about 38.9 mg / mL, about 39.0 mg / mL, about 39.1 mg / mL, about 39.2 mg / mL, about 39.3 mg / mL, about 39.4 mg / mL, or about 39.5 mg / mL squalene. In some embodiments, the emulsion comprises 38.5 mg / mL, 38.6 mg / mL, 38.7 mg / mL, 38.9 mg / mL, 39.0 mg / mL, 39.1 mg / mL, 39.2 mg / mL, 39.3 mg / mL, 39.4 mg / mL, or 39.5 mg / mL squalene. In some embodiments, the emulsion comprises 39.11 mg / mL squalene.

[0072] In some embodiments, the emulsion comprises the SLA adjuvant and DMPC. In some embodiments, the emulsion comprises about 4 mg / mL to about 9 mg / mL DMPC. In some embodiments, the emulsion comprises about 4 mg / mL to about 8.5 mg / mL, about 4 mg / mL to about 8 mg / mL, about 4 mg / mL to about 7.5 mg / mL, about 4 mg / mL to about 7 mg / mL, about 4 mg / mL to about 6.5 mg / mL, about 4 mg / mL to about 6 mg / mL, about 4 mg / mL to about 5.5 mg / mL, about 4 mg / mL to about 5 mg / mL, about 4 mg / mL to about 4.5 mg / mL, about 4.5 mg / mL to about 9 mg / mL, about 4.5 mg / mL to about 8.5 mg / mL, about 4.5 mg / mL to about 8 mg / mL, about 4.5 mg / mL to about 7.5 mg / mL, about 4.5Docket No.: CURV-010 / 02WO 340277-2148 mg / mL to about 7 mg / mL, about 4.5 mg / mL to about 6.5 mg / mL, about 4.5 mg / mL to about 6 mg / mL, about 4.5 mg / mL to about 5.5 mg / mL, about 4.5 mg / mL to about 5 mg / mL, about 5 mg / mL to about 9 mg / mL, about 5 mg / mL to about 8.5 mg / mL, about 5 mg / mL to about 8 mg / mL, about 5 mg / mL to about 7.5 mg / mL, about 5 mg / mL to about 7 mg / mL, about 5 mg / mL to about 6.5 mg / mL, about 5 mg / mL to about 6 mg / mL, about 5 mg / mL to about 5.5 mg / mL, about 5.5 mg / mL to about 9 mg / mL, about 5.5 mg / mL to about 8.5 mg / mL, about 5.5 mg / mL to about 8 mg / mL, about 5.5 mg / mL to about 7.5 mg / mL, about 5.5 mg / mL to about 7 mg / mL, about 5.5 mg / mL to about 7 mg / mL, about 5.5 mg / mL to about 6.5 mg / mL, about 5.5 mg / mL to about 6 mg / mL, about 6 mg / mL to about 9 mg / mL, about 6 mg / mL to about 8.5 mg / mL, about 6 mg / mL to about 8 mg / mL, about 6 mg / mL to about 7.5 mg / mL, about 6 mg / mL to about 7 mg / mL, about 6 mg / mL to about 6.5 mg / mL, about 6.5 mg / mL to about 9 mg / mL, about 6.5 mg / mL to about 8.5 mg / mL, about 6.5 mg / mL to about 8 mg / mL, about 6.5 mg / mL to about 7.5 mg / mL, about 6.5 mg / mL to about 7 mg / mL, about 7 mg / mL to about 9 mg / mL, about 7 mg / mL to about 8.5 mg / mL, about 7 mg / mL to about 8 mg / mL, about 7 mg / mL to about 7.5 mg / mL, about 7.5 mg / mL to about 9 mg / mL, about 7.5 mg / mL to about 8.5 mg / mL, about 7.5 mg / mL to about 8 mg / mL, about 8 mg / mL to about 9 mg / mL, about 8 mg / mL to about 8.5 mg / mL, about 8.5 mg / mL to about 9 mg / mL DMPC. In some embodiments, the emulsion comprises about 4 mg / mL, 4.5 mg / mL, 5 mg / mL, 5.5 mg / mL, 6 mg / mL, 6.5 mg / mL, 7 mg / mL, 7.5 mg / mL, 8 mg / mL, 8.5 mg / mL, or 9 mg / mL DMPC. In some embodiments, the emulsion comprises about 6.5, about 6.6, about 6.7, about 6.8, about 6.9, or about 7.0 mg / mL DMPC. In some embodiments, the emulsion comprises 6.5, 6.6, 6.7, 6.8, 6.9, or 7.0 mg / mL DMPC. In some embodiments, the emulsion comprises 6.84 mg / mL DMPC. In some embodiments, the emulsion comprises about 8.5 mg / mL, about 8.6 mg / mL, about 8.7 mg / mL, about 8.8 mg / mL, about 8.9 mg / mL, or about 9.0 mg / mL DMPC. In some embodiments, the emulsion comprises 8.5 mg / mL, 8.6 mg / mL, 8.7 mg / mL, 8.8 mg / mL, 8.9 mg / mL, or 9.0 mg / mL DMPC. In some embodiments, the emulsion comprises 8.74 mg / mL DMPC.

[0073] In some embodiments, the emulsion comprises the SLA adjuvant and poloxamer 188. In some embodiments, the emulsion comprises about 200 mcg / mL to about 400 mcg / mL. In some embodiments, the emulsion comprises about 225 mcg / mL to about 400 mcg / mL, about 250 mcg / mL to about 400 mcg / mL, about 250 mcg / mL to about 400 mcg / mL, about 275 mcg / mL to about 400 mcg / mL, about 300 mcg / mL to about 400 mcg / mL, about 325 mcg / mL to about 400 mcg / mL, about 350 mcg / mL to about 400 mcg / mL, about 375 mcg / mL to about 400 mcg / mL, about 200 mcg / mL to about 375 mcg / mL, about 225 mcg / mL to about 375 mcg / mL, about 250 mcg / mL to about 375 mcg / mL, about 275 mcg / mL to about 375 mcg / mL, about 300 mcg / mL to about 375 mcg / mL, about 325 mcg / mL to about 375 mcg / mL, about 350 mcg / mL to about 375Docket No.: CURV-010 / 02WO 340277-2148 mcg / mL, about 200 mcg / mL to about 350 mcg / mL, about 225 mcg / mL to about 350 mcg / mL, about 250 mcg / mL to about 350 mcg / mL, about 275 mcg / mL to about 350 mcg / mL, about 300 mcg / mL to about 350 mcg / mL, about 325 mcg / mL to about 350 mcg / mL, about 200 mcg / mL to about 325 mcg / mL, about 225 mcg / mL to about 325 mcg / mL, about 250 mcg / mL to about 325 mcg / mL, about 275 mcg / mL to about 325 mcg / mL, about 300 mcg / mL to about 325 mcg / mL, about 200 mcg / mL to about 300 mcg / mL, about 225 mcg / mL to about 300 mcg / mL, about 250 mcg / mL to about 300 mcg / mL, about 275 mcg / mL to about 300 mcg / mL, about 200 mcg / mL to about 275 mcg / mL, about 225 mcg / mL to about 275 mcg / mL, about 250 mcg / mL to about 275 mcg / mL, about 200 mcg / mL to about 250 mcg / mL, about 225 mcg / mL to about 250 mcg / mL, or about 200 mcg / mL to about 225 mcg / mL poloxamer 188. In some embodiments, the emulsion comprises about 300 mcg / mL, about 310 mcg / mL, about 320 mcg / mL, about 330 mcg / mL, about 340 mcg / mL, or about 350 mcg / mL poloxamer 188. In some embodiments, the emulsion comprises about 315 mcg / mL, about 316 mcg / mL, about 317 mcg / mL, about 318 mcg / mL, about 319 mcg / mL, about 320 mcg / mL, about 321 mcg / mL, about 322 mcg / mL, about 323 mcg / mL, about 324 mcg / mL, or about 325 mcg / mL poloxamer 188. In some embodiments, the emulsion comprises 315 mcg / mL, 316 mcg / mL, 317 mcg / mL, 318 mcg / mL, 319 mcg / mL, 320 mcg / mL, 321 mcg / mL, 322 mcg / mL, 323 mcg / mL, 324 mcg / mL, or 325 mcg / mL poloxamer 188. In some embodiments, the emulsion comprises 320 mcg / mL poloxamer 188.

[0074] In some embodiments, the emulsion comprises the SLA adjuvant and poloxamer 188. In some embodiments, the emulsion comprises about 200 mcg / mL to about 450 mcg / mL. In some embodiments, the emulsion comprises 350 mcg / mL, 360 mcg / mL, 370 mcg / mL, 380 mcg / mL, 390 mcg / mL, 400 mcg / mL, 410 mcg / mL, 420 mcg / mL, 430 mcg / mL, 440 mcg / mL, 450 mcg / mL poloxamer 188. In some embodiments, the emulsion comprises about 405 mcg / mL, about 406 mcg / mL, about 407 mcg / mL, about 408 mcg / mL, about 409 mcg / mL, about 410 mcg / mL, about 411 mcg / mL, about 412 mcg / mL, about 413 mcg / mL, about 414 mcg / mL, or about 415 mcg / mL poloxamer 188. In some embodiments, the emulsion comprises 405 mcg / mL, 406 mcg / mL, 407 mcg / mL, 408 mcg / mL, 409 mcg / mL, 410 mcg / mL, 411 mcg / mL, 412 mcg / mL, 413 mcg / mL, 414 mcg / mL, or 415 mcg / mL poloxamer 188. In some embodiments, the emulsion comprises 410 mcg / mL poloxamer 188. In some embodiments, the emulsion comprises 414 mcg / mL poloxamer 188.

[0075] In some embodiments, the emulsion comprises the SLA adjuvant and Vitamin E. In some embodiments, the emulsion comprises about 50 mcg / mL to about 200 mcg / mL Vitamin E. In some embodiments, the emulsion comprises about 50 mcg / mL to about 175 mcg / mL, about 50 mcg / mL to about 150 mcg / mL, about 50 mcg / mL to about 125 mcg / mL,Docket No.: CURV-010 / 02WO 340277-2148 about 50 mcg / mL to about 100 mcg / mL, about 50 mcg / mL to about 75 mcg / mL, about 75 mcg / mL to about 200 mcg / mL, about 75 mcg / mL to about 175 mcg / mL, about 75 mcg / mL to about 150 mcg / mL, about 75 mcg / mL to about 125 mcg / mL, about 75 mcg / mL to about 100 mcg / mL, about 100 mcg / mL to about 200 mcg / mL, about 100 mcg / mL to about 175 mcg / mL, about 100 mcg / mL to about 150 mcg / mL, about 100 mcg / mL to about 125 mcg / mL, about 125 mcg / mL to about 200 mcg / mL, about 125 mcg / mL to about 175 mcg / mL, about 125 mcg / mL to about 150 mcg / mL, about 150 mcg / mL to about 200 mcg / mL, about 150 mcg / mL to about 175 mcg / mL, or about 175 mcg / mL to about 200 mcg / mL. In some embodiments, the emulsion comprises about 50 mcg / mL, about 75 mcg / mL, about 100 mcg / mL, about 125 mcg / mL, about 150 mcg / mL, about 175 mcg / mL, or about 200 mcg / mL. In some embodiments, the emulsion comprises about 175 mcg / mL, about 176 mcg / mL, about 177 mcg / mL, about 178 mcg / mL, about 179 mcg / mL, about 180 mcg / mL, about 181 mcg / mL, about 182 mcg / mL, about 183 mcg / mL, about 184 mcg / mL, about 185 mcg / mL, about 186 mcg / mL, about 187 mcg / mL, about 188 mcg / mL, about 189 mcg / mL, or about 190 mcg / mL Vitamin E. In some embodiments, the emulsion comprises about 175 mcg / mL, about 176 mcg / mL, about 177 mcg / mL, about 178 mcg / mL, about 179 mcg / mL, about 180 mcg / mL, about 181 mcg / mL, about 182 mcg / mL, about 183 mcg / mL, about 184 mcg / mL, about 185 mcg / mL, about 186 mcg / mL, about 187 mcg / mL, about 188 mcg / mL, about 189 mcg / mL, or about 190 mcg / mL Vitamin E. In some embodiments, the emulsion comprises 175 mcg / mL, 176 mcg / mL, 177 mcg / mL, 178 mcg / mL, 179 mcg / mL, 180 mcg / mL, 181 mcg / mL, 182 mcg / mL, 183 mcg / mL, 184 mcg / mL, 185 mcg / mL, 186 mcg / mL, 187 mcg / mL, 188 mcg / mL, 189 mcg / mL, or 190 mcg / mL Vitamin E. In some embodiments, the emulsion comprises 180 mcg / mL Vitamin E.

[0076] In some embodiments, the emulsion comprises the SLA adjuvant and Vitamin E. In some embodiments, the emulsion comprises about 50 mcg / mL to about 250 mcg / mL Vitamin E. In some embodiments, the emulsion comprises 200 mcg / mL Vitamin E, 210 mcg / mL Vitamin E, 220 mcg / mL Vitamin E, 230 mcg / mL Vitamin E, 240 mcg / mL Vitamin E, or 250 mcg / mL Vitamin E. In some embodiments, the emulsion comprises about 225 mcg / mL, about 226 mcg / mL, about 227 mcg / mL, about 228 mcg / mL, about 229 mcg / mL, about 230 mcg / mL, about 231 mcg / mL, about 232 mcg / mL, about 233 mcg / mL, about 234 mcg / mL, about 235 mcg / mL, about 236 mcg / mL, about 237 mcg / mL, about 238 mcg / mL, about 239 mcg / mL, or about 240 mcg / mL Vitamin E. In some embodiments, the emulsion comprises 225 mcg / mL, 226 mcg / mL, 227 mcg / mL, 228 mcg / mL, 229 mcg / mL, 230 mcg / mL, 231 mcg / mL, 232 mcg / mL, 233 mcg / mL, 234 mcg / mL, 235 mcg / mL, 236 mcg / mL, 237 mcg / mL, 238 mcg / mL, 239 mcg / mL, or 240 mcg / mL Vitamin E. In some embodiments, the emulsion comprises 230 mcg / mL Vitamin E.Docket No.: CURV-010 / 02WO 340277-2148

[0077] In some embodiments, the emulsion comprises the SLA adjuvant to glycerol. In some embodiments, the emulsion comprises about 10 mg / mL to about 30 mg / mL glycerol. In some embodiments, the emulsion comprises about 10 mg / mL to about 27.5 mg / mL, about 10 mg / mL to about 25 mg / mL, about 10 mg / mL to about 22.5 mg / mL, about 10 mg / mL to about 20 mg / mL, about 10 mg / mL to about 17.5 mg / mL, about 10 mg / mL to about 15 mg / mL, about 10 mg / mL to about 12.5 mg / mL, about 12.5 mg / mL to about 30 mg / mL, about 12.5 mg / mL to about 27.5 mg / mL, about 12.5 mg / mL and about 25 mg / mL, about 12.5 mg / mL to about 22.5 mg / mL, about 12.5 mg / mL to about 20 mg / mL, about 12.5 mg / mL to about 17.5 mg / mL, about 12.5 mg / mL to about 15 mg / mL, about 15 mg / mL to about 30 mg / mL, about 15 mg / mL to about 27.5 mg / mL, about 15 mg / mL to about 25 mg / mL, about 15 mg / mL to about 22.5 mg / mL, about 15 mg / mL to about 20 mg / mL, about 15 mg / mL to about 17.5 mg / mL, about 17.5 mg / mL to about 30 mg / mL, about 17.5 mg / mL to about 27.5 mg / mL, about 17.5 mg / mL to about 25 mg / mL, about 17.5 mg / mL to about 22.5 mg / mL, about 17.5 mg / mL to about 20 mg / mL, about 20 mg / mL to about 30 mg / mL, about 20 mg / mL to about 27.5 mg / mL, about 20 mg / mL to about 25 mg / mL, about 20 mg / mL to about 22.5 mg / mL, about 22.5 mg / mL to about 20 mg / mL, about 22.5 mg / mL to about 27.5 mg / mL, about 22.5 mg / mL to about 25 mg / mL, about 25 mg / mL to about 30 mg / mL, about 25 mg / mL to about 27.5 mg / mL, or about 27.5 mg / mL to about 30 mg / mL glycerol. In some embodiments, the emulsion comprises about 10 mg / mL, about 12.5 mg / mL, about 15 mg / mL, about 17.5 mg / mL, about 20 mg / mL, about 22.5 mg / mL, about 25 mg / mL, about 27.5 mg / mL, or about 30 mg / mL glycerol. In some embodiments, the emulsion comprises about 20 mg / mL, about 20.1 mg / mL, about 20.2 mg / mL, about 20.3 mg / mL, about 20.4 mg / mL, about 20.5 mg / mL, about 20.6 mg / mL, about 20.7 mg / mL, about 20.8 mg / mL, about 20.9 mg / mL glycerol. In some embodiments, the emulsion comprises 20 mg / mL, 20.1 mg / mL, 20.2 mg / mL, 20.3 mg / mL, 20.4 mg / mL, 20.5 mg / mL, 20.6 mg / mL, 20.7 mg / mL, 20.8 mg / mL, 20.9 mg / mL glycerol. In some embodiments, the emulsion comprises 20.7 mg / mL glycerol. In some embodiments, the emulsion comprises c 26 mg / mL, about 26.1 mg / mL, about 26.2 mg / mL, about 26.3 mg / mL, about 26.4 mg / mL, about 26.5 mg / mL, about 26.6 mg / mL, about 26.7 mg / mL, about 26.8 mg / mL, about 26.9 mg / mL glycerol. In some embodiments, the emulsion comprises 26 mg / mL, 26.1 mg / mL, 26.2 mg / mL, 26.3 mg / mL, 26.4 mg / mL, 26.5 mg / mL, 26.6 mg / mL, 26.7 mg / mL, 26.8 mg / mL, 26.9 mg / mL glycerol. In some embodiments, the emulsion comprises 26.46 mg / mL glycerol.

[0078] In some embodiments, the emulsion comprises the SLA adjuvant and ammonium phosphate, monobasic. In some embodiments, the emulsion comprises about 1.5 mg / mL to about 3.5 mg / mL of ammonium phosphate monobasic. In some embodiments, the emulsion comprises about 1.5 mg / mL to about 3.25 mg / mL, about 1.5 mg / mL to about 3Docket No.: CURV-010 / 02WO 340277-2148 mg / mL, about 1.5 mg / mL to about 2.75 mg / mL, about 1.5 mg / mL to about 2.5 mg / mL, about 1.5 mg / mL to about 2.25 mg / mL, about 1.5 mg / mL to about 2 mg / mL, about 1.5 mg / mL to about 1.75 mg / mL, about 1.75 mg / mL to about 3.5 mg / mL, about 1.75 mg / mL to about 3.25 mg / mL, about 1.75 mg / mL to about 3 mg / mL, about 1.75 mg / mL to about 2.75 mg / mL, about 1.75 mg / mL to about 2.5 mg / mL, about 1.75 mg / mL to about 2.25 mg / mL, about 1.75 mg / mL to about 2 mg / mL, about 2 mg / mL to about 3.5 mg / mL, about 2 mg / mL to about 3.25 mg / mL, about 2 mg / mL to about 3 mg / mL, about 2 mg / mL to about 2.75 mg / mL, about 2 mg / mL to about 2.5 mg / mL, about 2 mg / mL to about 2.25 mg / mL, about 2.25 mg / mL to about 3.5 mg / mL, about 2.25 mg / mL to about 3.25 mg / mL, about 2.25 mg / mL to about 3 mg / mL, about 2.25 mg / mL to about 2.75 mg / mL, about 2.25 mg / mL to about 2.5 mg / mL, about 2.5 mg / mL to about 3.5 mg / mL, about 2.5 mg / mL to about 3.25 mg / mL, about 2.5 mg / mL to about 3 mg / mL, about 2.5 mg / mL to about 2.75 mg / mL, about 2.75 mg / mL to about 3.5 mg / mL, about 2.75 mg / mL to about 3.25 mg / mL, about 2.75 mg / mL to about 3 mg / mL, about 3 mg / mL to about 3.5 mg / mL, about 3 mg / mL to about 3.25 mg / mL, or about 3.25 mg / mL to about 3.5 mg / mL ammonium phosphate, monobasic. In some embodiments, the emulsion comprises about 1.5 mg / mL, about 1.75 mg / mL, about 2 mg / mL, about 2.25 mg / mL, about 2.5 mg / mL, about 3 mg / mL, about 3.25 mg / mL, or about 3.5 mg / mL ammonium phosphate, monobasic. In some embodiments, the emulsion comprises about 2.0 mg / mL, about 2.1 mg / mL, about 2.2 mg / mL, about 2.3 mg / mL, about 2.4 mg / mL, about 2.5 mg / mL, about 2.6 mg / mL, about 2.7 mg / mL, about 2.8 mg / mL, or about 2.9 mg / mL ammonium phosphate, monobasic. In some embodiments, the emulsion comprises about 2.40 mg / mL, about 2.41 mg / mL, about 2.42 mg / mL, about 2.43 mg / mL, about 2.44 mg / mL, about 2.45 mg / mL, about 2.46 mg / mL, about 2.47 mg / mL, about 2.48 mg / mL, or about 2.49 mg / mL ammonium phosphate, monobasic. In some embodiments, the emulsion comprises 2.40 mg / mL, 2.41 mg / mL, 2.42 mg / mL, 2.43 mg / mL, 2.44 mg / mL, 2.45 mg / mL, 2.46 mg / mL, 2.47 mg / mL, 2.48 mg / mL, or 2.49 mg / mL ammonium phosphate, monobasic. In some embodiments, the emulsion comprises 2.43 mg / mL ammonium phosphate, monobasic. In some embodiments, the emulsion comprises about 2.5 mg / mL ammonium phosphate, monobasic, about 2.6 mg / mL ammonium phosphate, monobasic, about 2.7 mg / mL ammonium phosphate, monobasic, about 2.8 mg / mL ammonium phosphate, monobasic, about 2.9 mg / mL ammonium phosphate, monobasic, about 3.0 mg / mL ammonium phosphate, monobasic, about 3.1 mg / mL ammonium phosphate, monobasic, about 3.2 mg / mL ammonium phosphate, monobasic, about 3.3 mg / mL ammonium phosphate, monobasic, about 3.4 mg / mL ammonium phosphate, monobasic, or about 3.5 mg / mL ammonium phosphate, monobasic. In some embodiments, the emulsion comprises about 3.05 mg / mL, about 3.06 mg / mL, about 3.07 mg / mL, about 3.08 mg / mL, about 3.09Docket No.: CURV-010 / 02WO 340277-2148 mg / mL, about 3.10 mg / mL, about 3.11 mg / mL, about 3.12 mg / mL, about 3.13 mg / mL, or about 3.14 mg / mL ammonium phosphate, monobasic. In some embodiments, the emulsion comprises 3.05 mg / mL, 3.06 mg / mL, 3.07 mg / mL, 3.08 mg / mL, 3.09 mg / mL, 3.10 mg / mL, 3.11 mg / mL, 3.12 mg / mL, 3.13 mg / mL, or 3.14 mg / mL ammonium phosphate, monobasic. In some embodiments, the emulsion comprises 3.11 mg / mL ammonium phosphate, monobasic.

[0079] In some embodiments, the emulsion comprises the SLA adjuvant and ammonium phosphate, dibasic. In some embodiments, the emulsion comprises about 50 mcg / mL to about 250 mcg / mL ammonium phosphate, dibasic. In some embodiments, the emulsion comprises about 50 mcg / mL to about 225 mcg / mL, about 50 mcg / mL to about 200 mcg / mL, about 50 mcg / mL to about 175 mcg / mL, about 50 mcg / mL to about 150 mcg / mL, about 50 mcg / mL to about 125 mcg / mL, about 50 mcg / mL to about 100 mcg / mL, about 50 mcg / mL to about 75 mcg / mL, about 75 mcg / mL to about 250 mcg / mL, about 75 mcg / mL to about 225 mcg / mL, about 75 mcg / mL to about 200 mcg / mL, about 75 mcg / mL to about 175 mcg / mL, about 75 mcg / mL to about 150 mcg / mL, about 75 mcg / mL to about 125 mcg / mL, about 75 mcg / mL to about 100 mcg / mL, about 100 mcg / mL to about 250 mcg / mL, about 100 mcg / mL to about 225 mcg / mL, about 100 mcg / mL to about 200 mcg / mL, about 100 mcg / mL to about 175 mcg / mL, about 100 mcg / mL to about 150 mcg / mL, about 100 mcg / mL to about 125 mcg / mL, about 125 mcg / mL to about 250 mcg / mL, about 125 mcg / mL to about 225 mcg / mL, about 125 mcg / mL to about 200 mcg / mL, about 125 mcg / mL to about 175 mcg / mL, about 125 mcg / mL to about 150 mcg / mL, about 150 mcg / mL to about 250 mcg / mL, about 150 mcg / mL to about 225 mcg / mL, about 150 mcg / mL to about 200 mcg / mL, about 150 mcg / mL to about 175 mcg / mL, about 175 mcg / mL to about 250 mcg / mL, about 175 mcg / mL to about 225 mcg / mL, about 175 mcg / mL to about 200 mcg / mL, about 200 mcg / mL to about 250 mcg / mL, about 200 mcg / mL to about 225 mcg / mL, or about 225 mcg / mL to about 250 mcg / mL ammonium phosphate, dibasic. In some embodiments, the emulsion comprises about 50 mcg / mL, about 75 mcg / mL, about 100 mcg / mL, about 125 mcg / mL, about 150 mcg / mL, about 175 mcg / mL, about 200 mcg / mL, about 225 mcg / mL, or about 250 mcg / mL ammonium phosphate, dibasic. In some embodiments, the emulsion comprises about 145 mcg / mL, about 146 mcg / mL, about 147 mcg / mL, about 148 mcg / mL, about 149 mcg / mL, about 150 mcg / mL, about 151 mcg / mL, about 152 mcg / mL, about 153 mcg / mL, about 154 mcg / mL, or about 155 mcg / mL ammonium phosphate, dibasic. In some embodiments, the emulsion comprises 145 mcg / mL, 146 mcg / mL, 147 mcg / mL, 148 mcg / mL, 149 mcg / mL, 150 mcg / mL, 151 mcg / mL, 152 mcg / mL, 153 mcg / mL, 154 mcg / mL, or 155 mcg / mL ammonium phosphate, dibasic. In some embodiments, the emulsion comprises 150 mcg / mL ammonium phosphate, dibasic. In some embodiments,Docket No.: CURV-010 / 02WO 340277-2148 the emulsion comprises 175 mcg / mL, 180 mcg / mL, 185 mcg / mL, 190 mcg / mL, 195 mcg / mL, 200 mcg / mL, 205 mcg / mL, 210 mcg / mL, 215 mcg / mL, 220 mcg / mL, or 225 mcg / mL ammonium phosphate, dibasic. In some embodiments, the emulsion comprises about 195 mcg / mL, about 196 mcg / mL, about 197 mcg / mL, about 198 mcg / mL, about 199 mcg / mL, about 200 mcg / mL, about 201 mcg / mL, about 202 mcg / mL, about 203 mcg / mL, about 204 mcg / mL, or about 205 mcg / mL ammonium phosphate, dibasic. In some embodiments, the emulsion comprises 195 mcg / mL, 196 mcg / mL, 197 mcg / mL, 198 mcg / mL, 199 mcg / mL, 200 mcg / mL, 201 mcg / mL, 202 mcg / mL, 203 mcg / mL, 204 mcg / mL, or 205 mcg / mL ammonium phosphate, dibasic. In some embodiments, the emulsion comprises 200 mcg / mL ammonium phosphate, dibasic. In some embodiments, the emulsion comprises 196 mcg / mL ammonium phosphate, dibasic.

[0080] In some embodiments, the emulsion comprises: (a) 18 mcg / mL of an SLA adjuvant of Formula (I) or a pharmaceutically acceptable salt thereof; (b) 30.6 mg / mL squalene; (c) 6.84 mg / mL DMPC, (d) 320 mcg / mL poloxamer 188, (e) 180 mcg / mL Vitamin E, (f) 20.7 mg / mL glycerol, (g) 2.43 mg / mL ammonium phosphate, monobasic; and (h) 150 mcg / mL ammonium phosphate, dibasic.

[0081] In some embodiments, the emulsion comprises: (a) 23 mcg / mL of an SLA adjuvant of Formula (I) or a pharmaceutically acceptable salt thereof; (b) 39.11 mg / mL squalene; (c) 8.74 mg / mL DMPC, (d) 410 mcg / mL poloxamer 188, (e) 230 mcg / mL Vitamin E, (f) 26.46 mg / mL glycerol, (g) 3.11 mg / mL ammonium phosphate, monobasic; and (h) 200 mcg / mL ammonium phosphate, dibasic.Docket No.: CURV-010 / 02WO 340277-2148 Immunogenic Compositions

[0082] In some embodiments, the present disclosure provides immunogenic compositions comprising a VZV antigen and an adjuvant. As used herein, the term “immunogenic” refers to the ability of an antigen (e.g., a polypeptide), to elicit an immune response, either a humoral or cellular immune response, and preferably both. In a preferred embodiment, the subject will display either a therapeutic or protective immunological response to administration of an “effective amount” or “immunologically effective amount” of an immunogenic composition herein such that resistance to new infection will be enhanced and / or the clinical severity of the disease will be reduced. The immunological response will normally be demonstrated by alleviation or elimination of at least one symptom associated with the infection.

[0083] As used herein, the term “vaccine” refers to an immunogenic composition which is used to induce an immune response that provides protective immunity against a pathogen (e.g., immunity that protects a subject against infection with the pathogen and / or reduces the severity of the disease or condition caused by infection with the pathogen). The protective immune response may include formation of antibodies and / or a cell-mediated response.

[0084] In some embodiments, the immunogenic compositions described herein are provided as a sterile formulation for administration to a subject, e.g., as a suspension, solution or in lyophilized form to be rehydrated prior to use.

[0085] In some embodiments, the immunogenic composition comprises: (a) about 110 mcg / mL to about 120 mcg / mL of a VZV-gE antigen comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 2; (b) about 15 mcg / mL to about 20 mcg / mL of an SLA adjuvant of Formula (I) or a pharmaceutically acceptable salt thereof; (c) an oil; (d) one or more excipients selected from NaCl, Na2HPO4· 2H2O, KH2PO4, sucrose, and L-Arginine monohydrochloride; and (e) one or more excipients selected from DMPC, poloxamer 188, Vitamin E, glycerol, and ammonium phosphate. In some embodiments, the immunogenic composition comprises each of NaCl, Na2HPO4· 2H2O, KH2PO4, sucrose, L-Arginine monohydrochloride, DMPC, poloxamer 188, Vitamin E, glycerol, and ammonium phosphate. In some embodiments, the oil is squalene.

[0086] In some embodiments, the immunogenic composition comprises (a) about 110 mcg / mL to about 120 mcg / mL of a VZV-gE antigen comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 2; (b) about 15 mcg / mL to about 20 mcg / mL of an SLA adjuvant; (c) about 25 mg / mL to about 35 mg / mL squalene; (d) about 3 mg to about 4 mg of NaCl NaCl; (e) about 0.3 mg to about 0.5 mg Na2HPO4· 2H2O; (f) about 0.04 mg to about 0.07 mg KH2PO4; (g) about 35 mg to about 45 mg sucrose; (h) about 5 mg to about 7 mg L-Arginine monohydrochloride; (i) about 5 mg / mL to about 8 mg / mLDocket No.: CURV-010 / 02WO 340277-2148 DMPC; (j) about 200 to 400 mcg / mL poloxamer 188; (k) about 50 mcg / mL to about 200 mcg / mL Vitamin E; (l) about 15 mg / mL to about 25 mg / mL glycerol; (m) about 1.5 mg / mL to about 3.5 mg / mL of ammonium phosphate, monobasic; and (n) about 0.05 mg / mL to about 2.5 mg / mL ammonium phosphate, dibasic.

[0087] In some embodiments, the immunogenic composition comprises (a) 115 mcg / mL of the VZV gE antigen; (b) about 17 mcg / mL of an SLA adjuvant of Formula (I) or a pharmaceutically acceptable salt thereof; (c) about 29.4 mg / mL squalene; (d) about 3.46 mg / mL of NaCl; (e) about 0.385 mg / mL Na2HPO4· 2H2O; (f) about 0.056 mg / mL KH2PO4; (g) about 38.5 mg / mL sucrose; (h) about 5.77 mg / mL L-Arginine monohydrochloride; (i) about 6.58 mg / mL DMPC; (j) about 310 mcg / mL poloxamer 188; (k) about 173 mcg / mL Vitamin E; (l) about 19.9 mg / mL glycerol; (m) about 2.34 mg / mL ammonium phosphate, monobasic; and (n) about 0.144 mg / mL ammonium phosphate, dibasic.

[0088] In some embodiments, the immunogenic composition comprises (a) about 110 mcg / mL to about 120 mcg / mL of a VZV-gE antigen comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 2; (b) about 15 mcg / mL to about 25 mcg / mL of an SLA adjuvant; (c) about 25 mg / mL to about 40 mg / mL squalene; (d) about 3 mg to about 4 mg of NaCl NaCl; (e) about 0.3 mg to about 0.5 mg Na2HPO4 · 2H2O; (f) about 0.04 mg to about 0.07 mg KH2PO4; (g) about 35 mg to about 45 mg sucrose; (h) about 5 mg to about 7 mg L-Arginine monohydrochloride; (i) about 5 mg / mL to about 10 mg / mL DMPC; (j) about 200 to 400 mcg / mL poloxamer 188; (k) about 50 mcg / mL to about 250 mcg / mL Vitamin E; (l) about 15 mg / mL to about 30 mg / mL glycerol; (m) about 1.5 mg / mL to about 3.5 mg / mL of ammonium phosphate, monobasic; and (n) about 0.05 mg / mL to about 2.5 mg / mL ammonium phosphate, dibasic.

[0089] In some embodiments, the immunogenic composition comprises (a) about 115 mcg / mL of the VZV gE antigen; (b) about 22 mcg / mL of an SLA adjuvant of Formula (I) or a pharmaceutically acceptable salt thereof; (c) about 37.6 mg / mL squalene; (d) about 3.46 mg / mL of NaCl; (e) about 0.385 mg / mL Na2HPO4· 2H2O; (f) about 0.056 mg / mL KH2PO4; (g) about 38.5 mg / mL sucrose; (h) about 5.77 mg / mL L-Arginine monohydrochloride; (i) about 8.4 mg / mL DMPC; (j) about 400 mcg / mL poloxamer 188; (k) about 221 mcg / mL Vitamin E; (l) about 25.4 mg / mL glycerol; (m) about 2.99 mg / mL ammonium phosphate, monobasic; and (n) about 0.192 mg / mL ammonium phosphate, dibasic. Stock Solution

[0090] In some embodiments, the present disclosure provides for a stock solution of adjuvant that can be diluted down to an appropriate concentration. In some embodiments, the adjuvant is SLA of Formula (I) or a pharmaceutically acceptable salt thereof. In someDocket No.: CURV-010 / 02WO 340277-2148 embodiments, the stock solution further comprises DMPC, vitamin E, squalene, glycerol, poloxamer 188, ammonium phosphate, monobasic, and ammonium phosphate, dibasic.

[0091] In some embodiments, the stock solution of the adjuvant comprises between 100- 200 mcg / ml SLA of Formula (I) or a pharmaceutically acceptable salt thereof. In some embodiments, the stock solution of the adjuvant comprises between 100-175 mcg / ml SLA. In some embodiments, the stock solution of the adjuvant comprises between 125- 175 mcg / ml SLA. In some embodiments, the stock solution of the adjuvant comprises between 145-155 mcg / ml SLA. In some embodiments, the stock solution comprises about 125 mcg / ml, about 130 mcg / ml, about 135 mcg / ml, about 140 mcg / ml, about 145 mcg / ml, about 150 mcg / ml, about 155 mcg / ml , about 160 mcg / ml, about 165 mcg / ml, about 170 mcg / ml, or about 175 mcg / ml SLA. In some embodiments, the stock solution of the adjuvant comprises 145 mcg / ml SLA, 146 mcg / ml SLA, 147 mcg / ml SLA, 148 mcg / ml SLA, 149 mcg / ml SLA, 150 mcg / ml SLA, 151 mcg / ml SLA, 152 mcg / ml SLA, 153 mcg / ml SLA, 154 mcg / ml SLA, or 155 mcg / ml SLA. In some embodiments, the stock solution of the adjuvant comprises 150 mcg / ml SLA.

[0092] In some embodiments, the stock solution comprises DMPC. In some embodiments, the stock solution comprises 30-75 mg / mL of DMPC. In some embodiments, the stock solution comprises 40-75 mg / mL of DMPC. In some embodiments, the stock solution comprises 50-75 mg / mL of DMPC. In some embodiments, the stock solution comprises 50-60 mg / mL of DMPC. In some embodiments, the stock solution comprises about 40 mg / mL DMPC, about 45 mg / mL DMPC, about 50 mg / mL DMPC, about 55 mg / mL DMPC, about 60 mg / mL DMPC, about 65 mg / mL DMPC, or about 70 mg / mL DMPC. In some embodiments, the stock solution comprises 50 mg / mL, 51 mg / mL, 52 mg / mL, 53 mg / mL, 54 mg / mL, 55 mg / mL, 56 mg / mL, 57 mg / mL, 58 mg / mL, 59 mg / mL, or 60 mg / mL DMPC. In some embodiments, the stock solution comprises 57 mg / mL DMPC.

[0093] In some embodiments, the stock solution comprises vitamin E. In some embodiments, the stock solution comprises 0.5-2.5 mg / mL of vitamin E. In some embodiments, the stock solution comprises 0.5-2.0 mg / mL of vitamin E. In some embodiments, the stock solution comprises 0.5-1.5 mg / mL of vitamin E. In some embodiments, the stock solution comprises 1.0-1.5 mg / mL of vitamin E. In some embodiments, the stock solution comprises about 0.5 mg / mL vitamin E, about 1 mg / mL vitamin E, about 1.5 mg / mL vitamin E, about 2 mg / mL vitamin E, or about 2.5 mg / mL vitamin E. In some embodiments, the stock solution comprises 1.0 mg / mL, 1.1 mg / mL, 1.2 mg / mL, 1.3 mg / mL, 1.4 mg / mL, 1.5 mg / mL, 1.6 mg / mL, 1.7 mg / mL, 1.8 mg / mL, 1.9 mg / mL, or 2.0 mg / mL vitamin E. In some embodiments, the stock solution comprises 1.5 mg / mL vitamin E.Docket No.: CURV-010 / 02WO 340277-2148

[0094] In some embodiments, the stock solution comprises squalene. In some embodiments, the stock solution comprises 150-450 mg / mL of squalene. In some embodiments, the stock solution comprises 150-350 mg / mL of squalene. In some embodiments, the stock solution comprises 200-300 mg / mL of squalene. In some embodiments, the stock solution comprises 225-275 mg / mL of squalene. In some embodiments, the stock solution comprises about 200 mg / mL squalene, about 210 mg / mL squalene, about 220 mg / mL squalene, about 230 mg / mL squalene, about 240 mg / mL squalene, about 250 mg / mL squalene, about 260 mg / mL squalene, about 270 mg / mL squalene, about 280 mg / mL squalene, about 290 mg / mL squalene, or about 300 mg / mL squalene. In some embodiments, the stock solution comprises 250 mg / mL, 251 mg / mL, 252 mg / mL, 253 mg / mL, 254 mg / mL, 255 mg / mL, 256 mg / mL, 257 mg / mL, 258 mg / mL, 259 mg / mL, or 260 mg / mL squalene. In some embodiments, the stock solution comprises 255 mg / mL squalene.

[0095] In some embodiments, the stock solution comprises glycerol. In some embodiments, the stock solution comprises 150-250 mg / mL of glycerol. In some embodiments, the stock solution comprises 150-200 mg / mL of glycerol. In some embodiments, the stock solution comprises 150-175 mg / mL of glycerol. In some embodiments, the stock solution comprises about 150 mg / mL glycerol, about 155 mg / mL glycerol, about 160 mg / mL glycerol, about 165 mg / mL glycerol, about 170 mg / mL glycerol, about 175 mg / mL glycerol, about 180 mg / mL glycerol, about 185 mg / mL glycerol, about 190 mg / mL glycerol, about 195 mg / mL glycerol, or about 200 mg / mL glycerol. In some embodiments, the stock solution comprises 172.0 mg / mL, 172.1 mg / mL, 172.2 mg / mL, 172.3 mg / mL, 172.4 mg / mL, 172.5 mg / mL, 172.6 mg / mL, 172.7 mg / mL, 172.8 mg / mL, 172.9 mg / mL, or 173.0 mg / mL glycerol. In some embodiments, the stock solution comprises 172.5 mg / mL glycerol.

[0096] In some embodiments, the stock solution comprises poloxamer 188. In some embodiments, the stock solution comprises 1.5-3.5 mg / mL of poloxamer 188. In some embodiments, the stock solution comprises 2.0-3.0 mg / mL of poloxamer 188. In some embodiments, the stock solution comprises 2.5-3.0 mg / mL of poloxamer 188. In some embodiments, the stock solution comprises about 0.5 mg / mL poloxamer 188, about 1.0 mg / mL poloxamer 188, about 1.5 mg / mL poloxamer 188, about 2.0 mg / mL poloxamer 188, about 2.5 mg / mL poloxamer 188, about 3.0 mg / mL poloxamer 188, about 3.5 mg / mL poloxamer 188, or about 4.0 mg / mL poloxamer 188. In some embodiments, the stock solution comprises 2.0 mg / mL, 2.1 mg / mL, 2.2 mg / mL, 2.3 mg / mL, 2.4 mg / mL, 2.5 mg / mL, 2.6 mg / mL, 2.7 mg / mL, 2.8 mg / mL, 2.9 mg / mL, or 3.0 mg / mL poloxamer 188. In some embodiments, the stock solution comprises 2.7 mg / mL poloxamer 188.Docket No.: CURV-010 / 02WO 340277-2148

[0097] In some embodiments, the stock solution comprises ammonium phosphate, monobasic. In some embodiments, the stock solution comprises 15-35 mg / mL of ammonium phosphate, monobasic. In some embodiments, the stock solution comprises 20-30 mg / mL of ammonium phosphate, monobasic. In some embodiments, the stock solution comprises 20-25 mg / mL of ammonium phosphate, monobasic. In some embodiments, the stock solution comprises about 15 mg / mL ammonium phosphate, monobasic, about 17.5 mg / mL ammonium phosphate, monobasic, about 20 mg / mL ammonium phosphate, monobasic, about 22.5 mg / mL ammonium phosphate, monobasic, about 25 mg / mL ammonium phosphate, monobasic, about 27.5 mg / mL ammonium phosphate, monobasic, about 30 mg / mL ammonium phosphate, monobasic, or about 32.5 mg / mL ammonium phosphate, monobasic. In some embodiments, the stock solution comprises 20.20 mg / mL, 20.21 mg / mL, 20.22 mg / mL, 20.23 mg / mL, 20.24 mg / mL, 20.25 mg / mL, 20.26 mg / mL, 20.27 mg / mL, 20.28 mg / mL, 20.29 mg / mL, or 20.30 mg / mL ammonium phosphate, monobasic. In some embodiments, the stock solution comprises 20.25 mg / mL ammonium phosphate, monobasic.

[0098] In some embodiments, the stock solution comprises ammonium phosphate, dibasic. In some embodiments, the stock solution comprises 0.25-2.0 mg / mL of ammonium phosphate, dibasic. In some embodiments, the stock solution comprises 0.5- 1.75 mg / mL of ammonium phosphate, dibasic. In some embodiments, the stock solution comprises 1-1.5 mg / mL of ammonium phosphate, dibasic. In some embodiments, the stock solution comprises about 0.25 mg / mL ammonium phosphate, dibasic, about 0.55 mg / mL ammonium phosphate, dibasic, about 0.75 mg / mL ammonium phosphate, dibasic, about 1.0 mg / mL ammonium phosphate, dibasic, about 1.25 mg / mL ammonium phosphate, dibasic, about 1.5 mg / mL ammonium phosphate, dibasic, about 1.75 mg / mL ammonium phosphate, dibasic, or about 2 mg / mL ammonium phosphate, dibasic. In some embodiments, the stock solution comprises 1.270 mg / mL,1.271 mg / mL, 1.272 mg / mL, 1.273 mg / mL, 1.274 mg / mL, 1.275 mg / mL, 1.276 mg / mL, 1.277 mg / mL, 1.278 mg / mL, 1.279 mg / mL, or 1.280 mg / mL ammonium phosphate, dibasic. In some embodiments, the stock solution comprises 1.275 mg / mL ammonium phosphate, dibasic.

[0099] In some embodiments, the stock solution of the adjuvant comprises between 20%- 50% SLA. In some embodiments, the stock solution of the adjuvant comprises between 20%-40% SLA. In some embodiments, the stock solution of the adjuvant comprises between 25%-40% SLA. In some embodiments, the stock solution of the adjuvant comprises between 25%-35% SLA. In some embodiments, the stock solution comprises about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, or about 35% SLA. In some embodiments, the stock solution of the adjuvant comprises 29.5% SLA, 29.6% SLA, 29.7% SLA, 29.8% SLA,Docket No.: CURV-010 / 02WO 340277-2148 29.9% SLA, 30.0% SLA, 30.1% SLA, 30.2% SLA, 30.3% SLA, 30.4% SLA, or 30.5% SLA. In some embodiments, the stock solution of the adjuvant comprises 30% SLA.

[0100] In some embodiments, the stock solution of the adjuvant comprises between 100- 175 mcg / ml SLA. In some embodiments, the stock solution comprises 30-75 mg / mL of DMPC. In some embodiments, the stock solution comprises 0.5-2.5 mg / mL of vitamin E. In some embodiments, the stock solution comprises 150-450 mg / mL of squalene. In some embodiments, the stock solution comprises 150-250 mg / mL of glycerol. In some embodiments, the stock solution comprises 1.5-3.5 mg / mL of poloxamer 188. In some embodiments, the stock solution comprises 15-35 mg / mL of ammonium phosphate, monobasic. In some embodiments, the stock solution comprises 0.25-2.0 mg / mL of ammonium phosphate, dibasic. In some embodiments, the stock solution of the adjuvant comprises about 150 mcg / ml SLA; about 57 mg / mL DMPC; about 1.5 mg / mL vitamin E; about 255 mg / mL squalene; about 172.5 mg / mL glycerol; about 2.7 mg / mL poloxamer 188; about 20.25 mg / mL ammonium phosphate, monobasic; and about 1.275 mg / mL ammonium phosphate, dibasic.

[0101] In some embodiments, the stock solution of the adjuvant comprises 150 mcg / ml SLA; 57 mg / mL DMPC; 1.5 mg / mL vitamin E; 255 mg / mL squalene; 172.5 mg / mL glycerol; 2.7 mg / mL poloxamer 188; 20.25 mg / mL ammonium phosphate, monobasic; and 1.275 mg / mL ammonium phosphate, dibasic. Administration and Use

[0102] In some embodiments, the present disclosure provides a method of preventing herpes zoster in a subject in need thereof comprising administration of an effective amount immunogenic composition or vaccine composition described herein. “Prevention,” as used herein, is used interchangeably with “prophylaxis” and can mean complete prevention of an infection or disease, or prevention of the development of symptoms of that infection or disease; a delay in the onset of an infection or disease or its symptoms; or a decrease in the severity of a subsequently developed infection or disease or its symptoms. In some embodiments, the present disclosure provides a method for reducing the risk of herpes zoster in a subject in need thereof comprising administering an effective amount of the immunogenic compositions described herein.

[0103] In some embodiments, the present disclosure provides methods for inducing a protective immune response against herpes zoster in a subject comprising administering to the subject an effective amount of the immunogenic or vaccine compositions described herein. In some embodiments, the protective immune response is indicated by an increase in anti-VZV gE antibody titers.Docket No.: CURV-010 / 02WO 340277-2148

[0104] The terms “treat,” “treatment,” and “treating,” as used herein, refer to an approach for obtaining beneficial or desired results, for example, clinical results. For the purposes of this disclosure, beneficia or desired results may include inhibiting or suppressing the initiation or progression of an infection or a disease; ameliorating, or reducing the development of, symptoms of an infection or disease; or a combination thereof.

[0105] As used herein, the term “subject” includes humans and other animals. Typically, the subject is a human. In some embodiments, the subject is 50 years aged or older. In some embodiments, the subject is 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80 years aged or older. In some embodiments, the subject is 55 years or older. In some embodiments, the subject is 60 years or older. In some embodiments, the subject is 65 years or older. In some embodiments, the subject is 70 years or older. In some embodiments, the subject is 75 years or older. In some embodiments, the subject is between 50 and 59 years old (inclusive of subjects aged 50 and 59). In some embodiments, the subject is between 60 and 69 years old (inclusive of subjects aged 60 and 69). In some embodiments, the subject is 70 years old or older. In some embodiments, the subject has had a prior VZV infection. In some embodiments, the subject has received one or more doses of Shingrix®. In other aspects, the subject is not a human; for example, a non-human primate; for example, a baboon, a chimpanzee, a gorilla, or a macaque.

[0106] In some embodiments, the subject is predisposed to herpes zoster as a result of any number of risk factors, including age and / or whether or not the subject is immunocompromised. In some embodiments, the subject is immunocompromised.

[0107] The “immunologically effective amount” or “effective amount” of the immunogenic or vaccine composition is an amount that, either as a single dose or as part of a series of two or more doses, is effective for preventing herpes zoster. Herein, the term “protective immune response” encompasses eliciting an anti-VZV antibody response in the subject. Antibody titers generated after administration of the immunogenic compositions described herein can be determined by means known in the art, for example by ELISA assays of serum samples derived from immunized subjects.

[0108] Administration of the immunogenic composition can be carried out using any effective mode of systemic delivery. The composition is usually administered parenterally, such as by injection, including intravenous, intramuscular, intraperitoneal, interstitial, or subcutaneous injection; injection may also be gingival, in which case the immunogenic composition is injected directly into the gum. The composition may, in addition, be administered transmucosally, such as via the intranasal, sublingual, transbuccal, intravaginal, or intrarectal routes. Other modes of administration are also envisioned, however, and the invention is not limited in this regard. By way of example,Docket No.: CURV-010 / 02WO 340277-2148 other modes of administration include oral and transdermal delivery as well as administration via inhalation or using a subdermal implant.

[0109] The mode of administration largely dictates the type of formulation or dosage form that comprises the immunogenic composition. Compositions formulated for parenteral administration include sterile aqueous and nonaqueous solutions, suspensions, and emulsions. Injectable aqueous solutions contain the active agent in water-soluble form. Examples of nonaqueous solvents or vehicles include fatty oils, such as olive oil and corn oil, synthetic fatty acid esters, such as ethyl oleate or triglycerides, low molecular weight alcohols such as propylene glycol, synthetic hydrophilic polymers such as polyethylene glycol, liposomes, and the like. Parenteral formulations may also contain excipients such as solubilizers, emulsifiers, stabilizers, preservatives, isotonicity agents, buffer systems, dispersants, diluents, viscosity modifiers, absorption enhancers, and combinations thereof. Injectable formulations are rendered sterile by incorporation of a sterilizing agent, filtration through a bacteria-retaining filter, irradiation, or heat. They can also be manufactured using a sterile injectable medium. The immunogenic composition or individual components thereof may also be in dried, e.g., lyophilized, form that may be rehydrated with a suitable vehicle immediately prior to administration via injection.

[0110] Of the transmucosal routes, intranasal administration is generally although not necessarily preferred. Intranasal formulations, including intranasally administered immunogenic compositions, are known in the art, and should be formulated with reference to the FDA’s Guidance for Industry: Nasal Spray and Inhalation Solution, Suspension, and Spray Drug Products. Intranasal formulations are liquids, i.e., solutions, emulsions, suspensions, or the like, for administration as sprays, intranasal injections, or drops, and can contain adjuvants and pharmaceutically acceptable excipients as above. Because of the relatively large size of the antigens in the formulation, systemic delivery via the intranasal route requires incorporation of a transmucosal absorption enhancer in the immunogenic composition. Examples of suitable transmucosal absorption enhancers include, without limitation, alkylsaccharides, cyclodextrins, and chitosans; see Maggio (2014) J. Excip. Food Chem.5(2): 100-12; and Merkus et al. (1999) Adv. Drug Deliv. Rev. 36: 41-57. The concentration of enhancer is selected to ensure that an immunologically effective amount of the formulation passes through the nasal membrane and into the systemic circulation at an efficient transport rate. Various anatomical and physiological considerations dictating the composition and nature of an intranasal immunogenic composition are discussed, for example, by Aurora (October 2002) Drug Development & Delivery 2(7), incorporated by reference herein.

[0111] Other modes of administration and corresponding formulations include, without limitation: sublingual administration with a rapidly dissolving dosage form such as aDocket No.: CURV-010 / 02WO 340277-2148 rapidly dissolving tablet; transbuccal administration using a buccal patch or other buccal delivery system; intravaginal administration using a pessary, ointment, or cream; intrarectal delivery using a rectal suppository, ointment, or cream; transdermal administration using a transdermal patch or formulation; subdermal administration with an injected implant or pellet; inhalation using a dry powder pulmonary formulation; and oral administration using an oral dosage form such as a tablet, capsule, or the like.

[0112] In some embodiments, the immunogenic composition is administered to a subject within the context of an appropriate dosage regimen. The composition may be administered once, or two or more times spaced out over an extended time period. For example, an initial, “prime” dose may be followed by at least one “boost” dose. In some embodiments, the methods provided herein comprise two or more administrations of the immunogenic compositions described herein. In some embodiments, the second administration of the immunogenic or vaccine composition is at least 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, or 8 weeks after the first administration. In some embodiments, the second administration of the immunogenic or vaccine composition is at least 50, at least 51, at least 52, at least 53, at least 54, at least 55, at least 56, at least 57, at least 58, at least 59, or at least 60 days after the first administration. In some embodiments, the second administration of the immunogenic or vaccine composition is 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, or 60 days after the first administration. In some embodiments, the second administration of the immunogenic or vaccine composition is 55 days after the first administration. In some embodiments, the second administration of the immunogenic or vaccine composition is 56 days after the first administration. In some embodiments, the second administration of the immunogenic or vaccine composition is 57 days after the first administration. In some embodiments, the second administration of the immunogenic or vaccine composition is 58 days after the first administration.

[0113] Regardless of the mode of administration, e.g., intramuscular injection or subcutaneous injection, or the like, the volume of a single dose of the vaccine will generally be in the range of about 1 μL to about 500 μL. In some embodiments, the volume is in the range of about 1 μL to about 250 μL. In some embodiments, the volume is in the range of about 2.5 μL to about 200 μL. In some embodiments, the volume is in the range of about 5 μL to about 150 μL. It will be appreciated that the concentration of total antigen in the immunogenic composition corresponds to an immunologically effective dose of the composition per unit volume, working from the aforementioned dose volume guidelines.

[0114] For ease of use, the immunogenic composition of the invention can be incorporated into a packaged product, or “kit,” including instructions for self-administrationDocket No.: CURV-010 / 02WO 340277-2148 or administration by a medical practitioner. The kit includes a sealed container housing a dose of the immunogenic composition, typically a “unit dose” appropriate for a single dosage event that is immunologically effective. The vaccine may be in liquid form and thus ready to administer as an injection or the like, or it may be in another form that requires the user to perform a preparation process prior to administration, e.g., hydration of a lyophilized formulation, activation of an inert component, or the like. The kit may also include two or more sealed containers with the prime dose in a first container and a boost dose in one or more additional containers.

[0115] It is to be understood that while the invention has been described in conjunction with a number of specific embodiments, the foregoing description as well as the experimental section that follows are intended to illustrate and not limit the scope of the invention. In this regard, no attempt is made to show details of the invention in more detail than is necessary for the fundamental understanding of the invention, the description taken with the drawings and / or examples making apparent to those skilled in the art how the invention may be embodied in practice. This disclosure includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the elements of the invention described herein are encompassed by the disclosure unless otherwise indicated herein or clearly contradicted by context. Doses

[0116] In some embodiments, the present disclosure provides a dose of the immunogenic compositions described herein comprising about 100 mcg of a Varicella- zoster virus gE glycoprotein (VZV-gE) antigen comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 2; and about 15 mcg of an SLA adjuvant. In some embodiments, the dose comprises about 101 mcg, 102 mcg, 103 mcg, 104 mcg, or 105 mcg. In some embodiments, the dose comprises about 15.1 mcg, 15.2 mcg, 15.3 mcg, 15.4 mcg, 15.5 mcg, 15.6 mcg, 15.7 mcg, 15.8 mcg, or 15.9 mcg of the SLA adjuvant.

[0117] In some embodiments, the present disclosure provides a dose of the immunogenic compositions described herein comprising about 100 mcg of a Varicella- zoster virus gE glycoprotein (VZV-gE) antigen comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 2; and about 20 mcg of an SLA adjuvant of Formula (I) or a pharmaceutically acceptable salt thereof. In some embodiments, the dose comprises about 101 mcg, 102 mcg, 103 mcg, 104 mcg, or 105 mcg. In some embodiments, the dose comprises about 19.6 mcg, 19.6 mcg, 19.7 mcg, 19.8 mcg, 19.9 mcg, 20.0 mcg, 20.1 mcg, 20.2 mcg, 20.3 mcg, 20.4 mcg, or 20.5 mcg of the SLA adjuvant of Formula (I) or a pharmaceutically acceptable salt thereof.Docket No.: CURV-010 / 02WO 340277-2148

[0118] In some embodiments, the dose is administered in a volume of about 900 μL. In some embodiments, the dose is administered in a volume of about 880 μL, 885 μL, 890 μL, 895 μL, 900 μL, 905 μL, 910 μL, 915 μL, or about 920 μL.

[0119] In some embodiments, the dose further comprises about 26.5 mg of squalene, about 3.12 mg of NaCl, about 0.346 mg Na2HPO4· 2H2O, about 0.050 mg KH2PO4, about 34.6 mg sucrose, about 5.19 mg L-Arginine monohydrochloride, about 5.92 mg DMPC, about 277 mcg poloxamer 188, about 156 mcg Vitamin E, about 17.9 mg glycerol, about 2.1 mg ammonium phosphate, monobasic, and about 0.13 mg ammonium phosphate, dibasic.

[0120] In some embodiments, the dose further comprises about 33.9 mg of squalene, about 3.12 mg of NaCl, about 0.346 mg Na2HPO4· 2H2O, about 0.050 mg KH2PO4, about 34.6 mg sucrose, about 5.19 mg L-Arginine monohydrochloride, about 7.56 mg DMPC, about 355 mcg poloxamer 188, about 199 mcg Vitamin E, about 22.9 mg glycerol, about 2.69 mg ammonium phosphate, monobasic, and about 0.17 mg ammonium phosphate, dibasic. INCORPORATION BY REFERENCE

[0121] All references, articles, publications, patents, patent publications, and patent applications cited herein are incorporated by reference in their entireties for all purposes. However, mention of any reference, article, publication, patent, patent publication, and patent application cited herein is not, and should not be taken as, an acknowledgment or any form of suggestion that they constitute valid prior art or form part of the common general knowledge in any country in the world. EXAMPLES

[0122] Amezosvatein safety, tolerability, and immunogenicity of 6 different dose combinations and antigen alone, versus placebo, was evaluated in a 90-participant Phase 1 clinical trial in a population of healthy adults, 18 to < 50 years of age. The vaccine was safe and well-tolerated in healthy adult participants at either dose level of SLA-SE (5 or 10 g) in combination with 25, 50, or 100 g of antigen. Amezosvatein elicited a robust humoral immune response and increased frequencies of CD4+ T cells expressing one or more cytokines among CD154, IFN , TNF , and IL-2 by ICS after peripheral bloodmononuclear cells (PBMC) were stimulated with gE peptide in healthy adults. On the basis of the observed safety, tolerability and immunogenicity data from the Phase 1 study,Docket No.: CURV-010 / 02WO 340277-2148 a Phase 2 study was initiated by studying two different antigen dose levels of Amezosvatein. Low-Dose antigen (50 g MG1120 + 5 g SLA-SE) vs. High-Dose antigen(100 g MG1120 + 5 g SLA-SE) were tested in a 1:1:1 randomization against Shingrix.

[0123] The Phase 2 Trial 1 enrolled Cohort 1 with 678 participants in a randomized, observer-blind study to evaluate the safety, tolerability and immunogenicity of the Low and High dose antigen arms of Amezosvatein compared to Shingrix in participants 50 years of age and older. Participants received vaccinations on Days 0 and 56. The safety and tolerability of both antigen dose levels of Amezosvatein as well as the comparator, Shingrix, will be observed throughout the study duration. Immunogenicity is measured primarily by Day 84 anti-gE ELISA antibody GMC (geometric mean concentration) responses and VRR (vaccine response rate). Secondarily, the immunogenicity in each arm is measured by anti-VZV neutralizing antibody, CMI (cell mediated immunity) consisting of gE specific CD4+ T cell frequency and VRR, and anti-gE ELISA antibody concentration fold rise.

[0124] Safety and immunogenicity endpoints in Cohort 1 were analyzed at Day 84. The Day 84 analysis was utilized to determine the Amezosvatein vaccine dose selected for future clinical development and determine if the criteria for non-inferiority of Amezosvatein compared to Shingrix were met.

[0125] The Amezosvatein Phase 2 Cohort 1 Day 84 data for safety, tolerability, and immunogenicity demonstrated the following summary points: (a) The safety and tolerability data demonstrate a favorable safety profile when compared with Shingrix for all solicited local and systemic reactogenicity in both Low Dose and High Dose antigen cohorts and across all age subgroups. (b) At Day 84, the High Dose and Low Dose antigen arms of Amezosvatein were non-inferior compared to Shingrix with regards to anti-gE antibody vaccine response rate (VRR). (c) A robust anti-gE antibody Geometric Mean Fold Rise (GMFR) >20 compared to Day 0, in both Low Dose and High Dose antigen cohorts and within each age subgroup consistent with a strong humoral response post vaccination. (d) The Day 84 anti-gE antibody GMC responses were higher in the High Dose antigen arm vs. the Low Dose antigen arm. (e) The Day 84 anti-gE antibody GMC responses were less than Shingrix in both Low Dose and High Dose antigen arms and did not achieve the non-inferiority threshold. (f) An age-related decrease was observed in the Day 84 anti-gE antibody GMC responses across the three age subgroups of 50-59; 60-69; and 70+.Docket No.: CURV-010 / 02WO 340277-2148 (g) The Day 84 anti-gE antibody GMC responses for Phase 2 Cohort 1 in both antigen dose arms were lower than what had been seen in comparable dose cohorts in the Phase 1 CRV-101-100 Study.

[0126] An analysis of the Phase 2 Cohort 1 data identified two primary explanations for the anti-gE antibody GMC data findings: (a) The observed age-related decrease in Day 84 anti-gE antibody GMC values suggests a significant contribution by immune-senescence. (b) The Phase 2 Cohort 1 the Amezosvatein Investigational Product contained an adjuvant formulation that had comparable levels of SLA to the Phase 1 study but a significant reduction in the squalene content.

[0127] These findings supported the Study Amendment to add three additional CRV-101 subject cohorts (Cohorts 2, 3, & 4), each receiving Amezosvatein containing High Antigen Dose (100 g MG1120) plus one of three adjuvant SLA-SE doses of 5 g, 10 g, and 15 grespectively. The squalene amount in the formulation for 5 g and 10 g SLA-SE wascomparable to the Phase 1 formulation. Subjects in the 50-59 and 60-69 year old age subgroups were enrolled in the Amendment #3 (Cohorts 2, 3, and 4). Subjects in the 70+ year-old age subgroup were not enrolled in the Amendment #3 cohorts. Safety and tolerability would be monitored in the same manner as cohort 1. All subjects enrolled under Amendment #3 will be followed to Day 421 and may continue in the same Long Term Follow-up Extension as Cohort 1.

[0128] The results of this amendment are intended to facilitate insight into the following: (a) The effect of higher adjuvant SLA doses to overcome immune-senescence (b) The effect of higher adjuvant SLA doses on safety and reactogenicity (c) The contribution of squalene to immunogenicity

[0129] A summary of the cohorts and study arms is provided in Table A below. Table A: Study ArmsDocket No.: CURV-010 / 02WO 340277-2148

[0130] Cohort 1 comprised of fixed adjuvant dose (5 g SLA) with two antigen doses(50 g (1B) and 100 g (1A) of MG1120 gE antigen) and Cohort 2 / 3 / 4 comprised fixedantigen dose (100 g MG1120) with three adjuvant doses (5 g (4A), 10 g (2A), and 15 g(3A) of SLA).

[0131] In Cohort 1, the immunogenicity objective was to demonstrate Amezosvatein Vaccine non-inferiority to Shingrix based on humoral immune responses and to evaluate safety and reactogenicity of two antigen dose levels of Amezosvatein compared to Shingrix in healthy adult participants 50 years of age. Non-inferiority was based on the co-primary endpoints of Month 3 anti-gE ELISA antibody concentration and vaccine response defined as a 4-fold or greater increase in anti-gE ELISA antibody concentrations from baseline to Month 3. The study is designed to rule out a 33% or greater relative decrease in the Month 3 anti-gE ELISA geometric mean concentration and to rule out a 10% or greater absolute decrease in the vaccine response rate. Anti-VZV neutralizing antibody and cell-mediated immunity responses will be evaluated as a secondary endpoint.

[0132] In Cohorts 2, 3, and 4 the immunogenicity objective is to identify an adjuvant dose that is more immunogenic than the 100 g MG1120 + 5 g SLA-SE formulation from Cohort 1 and has an immune response that is non-inferior to the Shingrix vaccine pooled from Cohort 1 through 4 in subjects 50 – 69 years of age. A given adjuvant dose was considered superior to the high antigen dose Cohort 1 formulation if the lower bound of the two-sided 80% confidence interval for the ratio of Day 84 anti-gE antibody GMC of new to old vaccine (Cohort 1, High Antigen Dose) was greater than 1.0. A given adjuvant dose was considered non-inferior to pooled Cohort 1-4 Shingrix, in the 50-69 age group, if the lower bound of the two-sided 80% confidence interval for the ratio of Day 84 anti- gE antibody GMC of the adjuvant dose to pooled Cohort 1-4 Shingrix was greater than 0.67. Anti-VZV neutralizing antibody and cell-mediated immune responses may be evaluated in one or more doses from cohorts 2, 3 or 4 to support the evaluation of the appropriate dose for further clinical development after anti-gE antibody results are evaluated.

[0133] Cohort 1 participants are randomized 1:1:1 to CRV-101 Vaccine high antigen dose(100 g MG1120 + 5 g SLA-SE), CRV-101 Vaccine low antigen dose (50 g MG1120 +5 g SLA-SE), or Shingrix. Both study vaccines, CRV-101 Vaccine and Shingrix, wereadministered by intramuscular injection on Day 0 and Day 56. Safety, reactogenicity, and immunogenicity analysis is ongoing and performed overall and by age group of 50 to <60, 60 to <70, and 70 years of age.

[0134] Cohort 2, 3, and 4 were designed to evaluate the safety, tolerability, andimmunogenicity of the High Antigen (100 g MG1120) dose component with threeDocket No.: CURV-010 / 02WO 340277-2148 adjuvant dose levels (SLA 10 g, 15 g, and 5 g with increased SE component (containing20 μL, 30 μL, and 20 μL squalene respectively). Participants were healthy adults aged 50 to <70 years of age, randomized 5:1 to arms within each cohort, CRV-101 Vaccine to Shingrix, and dosed with intramuscular injections on Day 0 and 56. Approximately 50% of each Cohort were 50 to <60, and 60 to <70.

[0135] Safety, reactogenicity and immunogenicity analysis were performed overall, by cohort, and grouped by 50 to <60, 60 to <70 years of age.

[0136] In Cohorts 1-4, participants were followed for safety, immunogenicity, and herpes zoster cases, from Day 0 to Day 421 [Month 14], and up to 5 additional years in the long term follow up (LTFU) extension period (LTFU year 2, 3, 4, 5, 6). Safety in the extension years consists of collection of SAEs and PIMMCs, and herpes zoster cases. Results

[0137] Results for the high dose antigen arm (100 g gE + 5 g SLA – Cohort 3A) compared to Shingrix are shown in FIG.1 – FIG.7. As shown, Cohort 3A demonstrated a non-inferior immune response to Shingrix.

[0138] FIG.1 shows that the primary immunogenicity endpoint of the magnitude of the humoral immune response was met and Amezosvatein demonstrated a non-inferior immune response to Shingrix. Similar results were achieved for the immune response increase from baseline (Geometric Mean Fold Rise – FIG.2A) and Vaccine response rate (FIG.2B - threshold of success defined as >4-fold rise in Geometric Mean Fold Rise (GMFR) in antibody response compared to pre-vaccination). Furthermore, plotting the anti-gE GMC ELISA values by age shows that there was no decline in the antibody response by age (FIG.3).

[0139] Furthermore, amezosvatein demonstrated an increase in tolerability, as indicated by a decrease in the reported adverse events. A summary of solicited systemic adverse events is provided in Table C and local adverse events in Table D. Table C: Solicited Systemic Adverse Events by GradeDocket No.: CURV-010 / 02WO 340277-2148Table D: Solicited Local Adverse Events by Grade

[0140] As shown in FIG. 4-FIG. 7, Amezosvatein has reduced adverse events vs. Shingrix within 7 days of either dose. FIG.4 shows the difference in all solicited adverse event, with a specific comparison of grade 2 / 3 adverse events between the two groups. FIG. 5 shows the comparisons for systemic adverse events. FIG. 6 shows the comparisons for local adverse events. FIG.7 shows comparisons between specific types of adverse events. In each comparison, Amezosvatein demonstrated reduced adverse events compared to those reported with Shingrix. Example 2: A Study to Evaluate Amezosvatein Compared with Shingrix® in Adults 50 Years of Age

[0141] A randomized, observer-blind, parallel group, active comparator, multi-center, Phase 3 study is planned to determine the immunogenicity and safety of amezosvatein compared to Shingrix. Participants 50 years of age will be enrolled. Participants 65 years of age will represent a minimum of 25% and a maximum of 30% of the total population enrolled, and participants 70 years of age will represent 10% of the total population enrolled.Docket No.: CURV-010 / 02WO 340277-2148

[0142] Participants will be randomized in a 1:1 ratio to receive amezosvatein or Shingrix. Randomization will be stratified by age and country. Each participant will receive 2 doses of vaccine: the first on Day 1, and the second on Day 57.

[0143] The total duration of the study for each participant is up to 226 days, including Screening on Day -1 and / or Day 1, vaccine administration on Day 1 and Day 57, and follow-up visits through Month 8 (Day 225). The study includes the following visits for each participant: clinic visits on Day -1 (if screening begins on Day -1), Day 1, Day 57, Day 85, and Day 225, and telephone contacts on Day 8, Day 29, Day 64, Day 113, and Day 169.

[0144] Serum will be collected at Day 1 and Day 85 from all participants for immunology assessments. Peripheral blood mononuclear cells will be collected at Day 1 and Day 85 from a subset of approximately 50% study participants and will be stored for potential exploratory analysis.

[0145] An eDiary will be used to solicit local and systemic reactogenicity AEs for 7 days after each study vaccine injection; unsolicited symptoms will be assessed for 28 days after each study vaccine injection. SAEs and PIMMCs will be recorded and monitored from the time of signing the informed consent through the end-of-study (EOS) or early discontinuation. MAAEs will be monitored from Day 1 post vaccination through the EOS or early discontinuation.

[0146] Between approximately 550 and 750 participants will be enrolled. This represents a planned overall power of 90% or greater to confirm non-inferiority in anti-gE ELISA antibody GMC ratio of amezosvatein vs. Shingrix.

[0147] Study arms of the Phase 3 trial are summarized in Table B. Table B: Study summaryNUMBERED EMBODIMENTS

[0148] Embodiment 1: A lyophilized composition comprising: about 110 mcg to about 130 mcg of a Varicella-zoster virus gE glycoprotein (VZV-gE) antigen comprising an amino acidDocket No.: CURV-010 / 02WO 340277-2148 sequence that is at least 95% identical to SEQ ID NO: 2; one or more excipients selected from sodium chloride (NaCl), disodium hydrogen phosphate dihydrate (Na2HPO4 · 2H2O), potassium dihydrogen phosphate (KH2PO4), sucrose, and L-Arginine monohydrochloride.

[0149] Embodiment 2: The lyophilized composition of embodiment 1, comprising each of NaCl, Na2HPO4 · 2H2O, KH2PO4, sucrose, and L-Arginine monohydrochloride.

[0150] Embodiment 3: The lyophilized composition of embodiment 1 or embodiment 2, comprising about 3 mg to about 4 mg of NaCl.

[0151] Embodiment 4: The lyophilized composition of embodiment 3, comprising about 3.6 mg NaCl.

[0152] Embodiment 5: The lyophilized composition of any one of embodiments 1-4, comprising about 0.3 mg to about 0.5 mg Na2HPO4 · 2H2O.

[0153] Embodiment 6: The lyophilized composition of embodiment 5, comprising about 0.4 mg Na2HPO4 · 2H2O

[0154] Embodiment 7: The lyophilized composition of any one of embodiments 1-6, comprising about 0.04 mg to about 0.07 mg KH2PO4.

[0155] Embodiment 8: The lyophilized composition of embodiment 7, comprising about 0.058 mg KH2PO4.

[0156] Embodiment 9: The lyophilized composition of any one of embodiments 1-8, comprising about 35 mg to about 45 mg sucrose.

[0157] Embodiment 10: The lyophilized composition of embodiment 9, comprising about 40 mg sucrose.

[0158] Embodiment 11: The lyophilized composition of any one of embodiments 1-10, comprising about 5 mg to about 7 mg L-Arginine monohydrochloride.

[0159] Embodiment 12: The lyophilized composition of embodiment 11, comprising about 6 mg L-Arginine monohydrochloride.

[0160] Embodiment 13: The lyophilized composition of any one of embodiments 1-12, comprising about 120 mcg of the VZV-gE antigen.

[0161] Embodiment 14: A lyophilized composition comprising: about 110 mcg to about 130 mcg of a Varicella-zoster virus gE glycoprotein (VZV-gE) antigen comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 2; about 3 mg to about 4 mg of NaCl; about 0.3 mg to about 0.5 mg Na2HPO4 · 2H2O; about 0.04 to about 0.07 mg KH2PO4; about 35 mg to about 45 mg sucrose; and about 5 mg to about 7 mg L-Arginine monohydrochloride.

[0162] Embodiment 15: The lyophilized composition of embodiment 14, comprising: about 120 mcg of the VZV-gE antigen; about 3.6 mg NaCl; about 0.4 mg Na2HPO4 · 2H2O; about 0.058 mg KH2PO4; about 40 mg sucrose; and about 6 mg L-Arginine monohydrochloride.

[0163] Embodiment: 16: An emulsion composition comprising: about 15 mcg / mL to about 20 mcg / mL of an SLA adjuvant; an oil; and one or more excipients selected from 1,2-Dimyristoyl-Docket No.: CURV-010 / 02WO 340277-2148 sn-glycero-3-phosphocholine (DMPC), poloxamer 188, Vitamin E, glycerol, and ammonium phosphate.

[0164] Embodiment 17: The emulsion composition of embodiment 16, wherein the oil is squalene and wherein the composition comprises about 25 mg / mL to about 40 mg / mL squalene.

[0165] Embodiment 18: The emulsion composition of embodiment 17, wherein the composition comprises about 30.6 mg / mL squalene.

[0166] Embodiment 19: The emulsion composition of embodiment 17, the emulsion composition comprises about 39.11 mg / mL squalene.

[0167] Embodiment 20: The emulsion composition of any one of embodiments 16-19, comprising about 5 mg / mL to about 9 mg / mL DMPC.

[0168] Embodiment 21: The emulsion composition of embodiment 20, comprising about 6.84 mg / mL DMPC.

[0169] Embodiment 22: The emulsion composition of embodiment 20, comprising about 8.74 mg / mL DMPC.

[0170] Embodiment 23: The emulsion composition of any one of embodiments 16-22, comprising about 200 to 450 mcg / mL poloxamer 188.

[0171] Embodiment 24: The emulsion composition of embodiment 23, comprising about 320 mcg / mL poloxamer 188.

[0172] Embodiment 25: The emulsion composition of embodiment 23, comprising about 410 mcg / mL poloxamer 188.

[0173] Embodiment 26: The emulsion composition of any one of embodiments 16-25, comprising about 50 mcg / mL to about 250 mcg / mL Vitamin E.

[0174] Embodiment 27: The emulsion composition of embodiment 26, comprising about 180 mcg / mL Vitamin E.

[0175] Embodiment 28: The emulsion composition of embodiment 26, comprising about 230 mcg / mL Vitamin E.

[0176] Embodiment 29: The emulsion composition of any one of embodiments 16-28, comprising about 15 mg / mL to about 30 mg / mL glycerol.

[0177] Embodiment 30: The emulsion composition of embodiment 29, comprising about 20.7 mg / mL glycerol.

[0178] Embodiment 31: The emulsion composition of embodiment 29, comprising about 26.46 mg / mL glycerol.

[0179] Embodiment 32: The emulsion composition of any one of embodiments 16-31, wherein the ammonium phosphate comprises ammonium phosphate, monobasic and ammonium phosphate, dibasic.Docket No.: CURV-010 / 02WO 340277-2148

[0180] Embodiment 33: The emulsion composition of embodiment 32, comprising about 1.5 mg / mL to about 3.5 mg / mL of ammonium phosphate, monobasic and about 0.05 mg / mL to about 2.5 mg / mL of ammonium phosphate, dibasic.

[0181] Embodiment 34: The emulsion composition of embodiment 33, comprising about 2.43 mg / mL ammonium phosphate, monobasic and about 0.15 mg / mL ammonium phosphate, dibasic.

[0182] Embodiment 35: The emulsion composition of embodiment 33, comprising about 3.11 mg / mL ammonium phosphate, monobasic and about 0.2 mg / mL ammonium phosphate, dibasic.

[0183] Embodiment 36: The emulsion of any one of embodiments 16-35, comprising: 18 mcg / mL of an SLA adjuvant; 30.6 mg / mL squalene; 6.84 mg / mL DMPC; 320 mcg / mL poloxamer 188; 180 mcg / mL Vitamin E; 20.7 mg / mL glycerol; 2.43 mg / mL ammonium phosphate, monobasic; and 150 mcg / mL ammonium phosphate, dibasic.

[0184] Embodiment 37: The emulsion of any one of embodiments 16-35, comprising: 23 mcg / mL of an SLA adjuvant; 39.11 mg / mL squalene; 8.74 mg / mL DMPC; 41 mcg / mL poloxamer 188; 230 mcg / mL Vitamin E; 26.46 mg / mL glycerol; 3.11 mg / mL ammonium phosphate, monobasic; and 200 mcg / mL ammonium phosphate, dibasic.

[0185] Embodiment 38: The emulsion of any one of embodiments 16-37, wherein the SLA adjuvant has the following structure:Docket No.: CURV-010 / 02WO 340277-2148

[0186] Embodiments 39: An immunogenic composition comprising: about 110 mcg / mL to about 120 mcg / mL of a Varicella-zoster virus gE glycoprotein (VZV-gE) antigen comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 2; about 15 mcg / mL to about 25 mcg / mL of an SLA adjuvant; an oil; one or more excipients selected from sodium chloride (NaCl), disodium hydrogen phosphate dihydrate (Na2HPO4 · 2H2O), potassium dihydrogen phosphate (KH2PO4), sucrose, and L-Arginine monohydrochloride; and one or more excipients selected from 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC), poloxamer 188, Vitamin E, glycerol, and ammonium phosphate.

[0187] Embodiment 40: The immunogenic composition of embodiment 39, comprising each of NaCl, Na2HPO4 · 2H2O, KH2PO4, sucrose, L-Arginine monohydrochloride, DMPC, poloxamer 188, Vitamin E, glycerol, and ammonium phosphate.

[0188] Embodiment 41: The immunogenic composition of embodiment 39 or 40, comprising about 25 mg / mL to about 40 mg / mL squalene.

[0189] Embodiment 42: The immunogenic of embodiment 41, comprising about 29.4 mg / mL squalene.

[0190] Embodiment 43: The immunogenic of embodiment 41, comprising about 37.6 mg / mL squalene

[0191] Embodiment 44: The immunogenic composition of any one of embodiments 39-42, comprising about 115 mcg / mL of a VZV gE antigen.

[0192] Embodiment 45: The immunogenic composition of embodiment 39 or 44, comprising about 3 mg to about 4 mg of NaCl; about 0.3 mg to about 0.5 mg Na2HPO4 · 2H2O; about 0.04 mg to about 0.07 mg KH2PO4; 35 mg to about 45 mg sucrose; about 5 mg to about 7 mg L-Arginine monohydrochloride; about 5 mg / mL to about 9 mg / mL DMPC; about 200 mcg / mL to about 450 mcg / mL poloxamer 188; about 50 mcg / mL to about 250 mcg / mL Vitamin E; about 15 mg / mL to about 30 mg / mL glycerol; about 1.5 mg / mL to about 3.5 mg / mL of ammonium phosphate, monobasic; and about 0.05 mg / mL to about 2.5 mg / mL ammonium phosphate, dibasic.

[0193] Embodiment 46: The immunogenic composition of embodiment 39 or 45, comprising about 3.46 mg / mL of NaCl; about 0.385 mg / mL Na2HPO4 · 2H2O; about 0.056 mg / mL KH2PO4;

[0194] about 38.5 mg / mL sucrose; about 5.76 mg / mL L-Arginine monohydrochloride; about 6.58 mg / mL DMPC; about 310 mcg / mL poloxamer 188; about 173 mcg / mL Vitamin E; about 19.9 mg / mL glycerol; about 2.34 mg / mL ammonium phosphate, monobasic; and about 0.144 mg / mL ammonium phosphate, dibasic.

[0195] Embodiment 47: The immunogenic composition of embodiment 39 or 45, comprising about 3.46 mg / mL of NaCl; about 0.385 mg / mL Na2HPO4 · 2H2O; about 0.056 mg / mL KH2PO4; about 38.5 mg / mL sucrose; about 5.76 mg / mL L-Arginine monohydrochloride; aboutDocket No.: CURV-010 / 02WO 340277-2148 8.4 mg / mL DMPC; about 310 mcg / mL poloxamer 188; about 221 mcg / mL Vitamin E; about 25.4 mg / mL glycerol; about 2.99 mg / mL ammonium phosphate, monobasic; and about 0.192 mg / mL ammonium phosphate, dibasic.

[0196] Embodiment 48: The immunogenic composition of any one of embodiment 39-47, wherein the SLA adjuvant has the following structure:(Formula II)

[0197] Embodiment 49: A dose of an immunogenic composition comprising: about 100, 101, 102, or 103 mcg of a Varicella-zoster virus gE glycoprotein (VZV-gE) antigen comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 2; about 15 mcg of an SLA adjuvant; about 26.5 mg of squalene; about 3.12 mg of NaCl; about 0.346 mg Na2HPO4 · 2H2O; about 0.050 mg KH2PO4; about 34.6 mg sucrose; about 5.19 mg L-Arginine monohydrochloride; about 5.92 mg DMPC; about 277 mcg poloxamer 188; about 156 mcg Vitamin E; about 17.9 mg glycerol; about 2.1 mg ammonium phosphate, monobasic; and about 0.13 mg ammonium phosphate, dibasic.

[0198] Embodiment 50: A dose of an immunogenic composition comprising: about 100, 101, 102, or 103 mcg of a Varicella-zoster virus gE glycoprotein (VZV-gE) antigen comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 2; about 19.9 mcg of an SLA adjuvant; about 33.8 mg of squalene; about 3.12 mg of NaCl; about 0.346 mg Na2HPO4 · 2H2O; about 0.050 mg KH2PO4; about 34.6 mg sucrose; about 5.19 mg L-Arginine monohydrochloride; about 7.56 mg DMPC; about 355 mcg poloxamer 188; about 199 mcgDocket No.: CURV-010 / 02WO 340277-2148 Vitamin E; about 22.9 mg glycerol; about 2.69 mg ammonium phosphate, monobasic; and about 0.17 mg ammonium phosphate, dibasic.

[0199] Embodiment 51: A pre-filled syringe comprising the dose of any one of embodiments 49 or 50.

[0200] Embodiment 52: A method of preventing Herpes Zoster in a subject in need thereof, comprising administration of the dose of any one of embodiments 49 or 50.

[0201] Embodiment 53: The method of embodiment 52, further comprising administration of a second dose according to any one of embodiments 49 or 50.

[0202] Embodiment 54: The method of embodiment 53, wherein the first and second doses are administered at least 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, or 8 weeks apart.

[0203] Embodiment 55: The method of any one of embodiments 51 - 54, wherein the subject has not previously received a dose of Shingrix®.

[0204] Embodiments 56: The method of any one of embodiments 51 - 54, wherein the subject has previously received one or more doses of Shingrix®.

[0205] Embodiments 57: The method of any one of embodiments 51 - 56, wherein the administration is subcutaneous or intramuscular.58. A stock solution comprising a second- generation lipid adjuvant (SLA), 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC), vitamin E, squalene, glycerol, poloxamer 188, ammonium phosphate, monobasic, and / or ammonium phosphate, dibasic; wherein the SLA comprises the structure set forth in Formula I or Formula II(Formula II).

[0206] Embodiment 59: The stock solution of embodiment 58, wherein the stock solution comprises: about 100 to about 200 mcg / ml SLA; about 25 to about 75 mg / mL DMPC; aboutDocket No.: CURV-010 / 02WO 340277-2148 0.5 to 2.5 mg / mL vitamin E; about 150 to 300 mg / mL squalene; about 150 to 250 mg / mL glycerol; about 1.5 to 3.5 mg / mL poloxamer 188; about 15 to 25 mg / mL ammonium phosphate, monobasic; and / or about 0.5 to 2.5 mg / mL ammonium phosphate, dibasic.

[0207] Embodiment 60: The stock solution of embodiment 58 or 59, wherein the stock solution comprises: 150 mcg / ml SLA; 57 mg / mL DMPC; 1.5 mg / mL vitamin E; 255 mg / mL squalene; 172.5 mg / mL glycerol; 2.7 mg / mL poloxamer 188; 20.25 mg / mL ammonium phosphate, monobasic; and1.275 mg / mL ammonium phosphate, dibasic.

Claims

Docket No.: CURV-010 / 02WO 340277-2148 CLAIMS 1. A lyophilized composition comprising: about 110 mcg to about 130 mcg of a Varicella-zoster virus gE glycoprotein (VZV- gE) antigen comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 2; one or more excipients selected from sodium chloride (NaCl), disodium hydrogen phosphate dihydrate (Na2HPO4· 2H2O), potassium dihydrogen phosphate (KH2PO4), sucrose, and L-Arginine monohydrochloride.

2. The lyophilized composition of claim 1, comprising each of NaCl, Na2HPO4· 2H2O, KH2PO4, sucrose, and L-Arginine monohydrochloride.

3. The lyophilized composition of claim 1 or claim 2, comprising about 3 mg to about 4 mg of NaCl.

4. The lyophilized composition of claim 3, comprising about 3.6 mg NaCl.

5. The lyophilized composition of any one of claims 1-4, comprising about 0.3 mg to about 0.5 mg Na2HPO4· 2H2O.

6. The lyophilized composition of claim 5, comprising about 0.4 mg Na2HPO4· 2H2O 7. The lyophilized composition of any one of claims 1-6, comprising about 0.04 mg to about 0.07 mg KH2PO4.

8. The lyophilized composition of claim 7, comprising about 0.058 mg KH2PO4.

9. The lyophilized composition of any one of claims 1-8, comprising about 35 mg to about 45 mg sucrose.

10. The lyophilized composition of claim 9, comprising about 40 mg sucrose.

11. The lyophilized composition of any one of claims 1-10, comprising about 5 mg to about 7 mg L-Arginine monohydrochloride.

12. The lyophilized composition of claim 11, comprising about 6 mg L-Arginine monohydrochloride.

13. The lyophilized composition of any one of claims 1-12, comprising about 120 mcg of the VZV-gE antigen.

14. A lyophilized composition comprising:Docket No.: CURV-010 / 02WO 340277-2148 about 110 mcg to about 130 mcg of a Varicella-zoster virus gE glycoprotein (VZV- gE) antigen comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 2; about 3 mg to about 4 mg of NaCl; about 0.3 mg to about 0.5 mg Na2HPO4· 2H2O; about 0.04 to about 0.07 mg KH2PO4; about 35 mg to about 45 mg sucrose; and about 5 mg to about 7 mg L-Arginine monohydrochloride.

15. The lyophilized composition of claim 14, comprising: about 120 mcg of the VZV-gE antigen; about 3.6 about 0.4· 2H2O; about 0.058 mg KH2PO4; about 40 mg sucrose; and about 6 mg L-Arginine monohydrochloride.

16. An emulsion composition comprising: about 15 mcg / mL to about 20 mcg / mL of an SLA adjuvant; an oil; and one or more excipients selected from 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC), poloxamer 188, Vitamin E, glycerol, and ammonium phosphate.

17. The emulsion composition of claim 16, wherein the oil is squalene and wherein the composition comprises about 25 mg / mL to about 40 mg / mL squalene.

18. The emulsion composition of claim 17, wherein the composition comprises about 30.6 mg / mL squalene.

19. The emulsion composition of claim 17, the emulsion composition comprises about 39.11 mg / mL squalene.

20. The emulsion composition of any one of claims 16-19, comprising about 5 mg / mL to about 9 mg / mL DMPC.

21. The emulsion composition of claim 20, comprising about 6.84 mg / mL DMPC.

22. The emulsion composition of claim 20, comprising about 8.74 mg / mL DMPC.

23. The emulsion composition of any one of claims 16-22, comprising about 200 to 450 mcg / mL poloxamer 188.Docket No.: CURV-010 / 02WO 340277-2148 24. The emulsion composition of claim 23, comprising about 320 mcg / mL poloxamer 188.

25. The emulsion composition of claim 23, comprising about 410 mcg / mL poloxamer 188.

26. The emulsion composition of any one of claims 16-25, comprising about 50 mcg / mL to about 250 mcg / mL Vitamin E.

27. The emulsion composition of claim 26, comprising about 180 mcg / mL Vitamin E.

28. The emulsion composition of claim 26, comprising about 230 mcg / mL Vitamin E.

29. The emulsion composition of any one of claims 16-28, comprising about 15 mg / mL to about 30 mg / mL glycerol.

30. The emulsion composition of claim 29, comprising about 20.7 mg / mL glycerol.

31. The emulsion composition of claim 29, comprising about 26.46 mg / mL glycerol.

32. The emulsion composition of any one of claims 16-31, wherein the ammonium phosphate comprises ammonium phosphate, monobasic and ammonium phosphate, dibasic.

33. The emulsion composition of claim 32, comprising about 1.5 mg / mL to about 3.5 mg / mL of ammonium phosphate, monobasic and about 0.05 mg / mL to about 2.5 mg / mL of ammonium phosphate, dibasic.

34. The emulsion composition of claim 33, comprising about 2.43 mg / mL ammonium phosphate, monobasic and about 0.15 mg / mL ammonium phosphate, dibasic.

35. The emulsion composition of claim 33, comprising about 3.11 mg / mL ammonium phosphate, monobasic and about 0.2 mg / mL ammonium phosphate, dibasic.

36. The emulsion of any one of claims 16-35, comprising: 18 mcg / mL of an SLA adjuvant; 30.6 mg / mL squalene; 6.84 mg / mL DMPC, 320 mcg / mL poloxamer 188, 180 mcg / mL Vitamin E, 20.7 mg / mL glycerol, 2.43 mg / mL ammonium phosphate, monobasic; and 150 mcg / mL ammonium phosphate, dibasic.

37. The emulsion of any one of claims 16-35, comprising:Docket No.: CURV-010 / 02WO 340277-2148 23 mcg / mL of an SLA adjuvant; 39.11 mg / mL squalene; 8.74 mg / mL DMPC, 41 mcg / mL poloxamer 188, 230 mcg / mL Vitamin E, 26.46 mg / mL glycerol, 3.11 mg / mL ammonium phosphate, monobasic; and 200 mcg / mL ammonium phosphate, dibasic.

38. The emulsion of any one of claims 16-37, wherein the SLA adjuvant has the following structure:

39. An immunogenic composition comprising: about 110 mcg / mL to about 120 mcg / mL of a Varicella-zoster virus gE glycoprotein (VZV-gE) antigen comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 2; about 15 mcg / mL to about 25 mcg / mL of an SLA adjuvant; an oil;Docket No.: CURV-010 / 02WO 340277-2148 one or more excipients selected from sodium chloride (NaCl), disodium hydrogen phosphate dihydrate (Na2HPO4· 2H2O), potassium dihydrogen phosphate (KH2PO4), sucrose, and L-Arginine monohydrochloride; and one or more excipients selected from 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC), poloxamer 188, Vitamin E, glycerol, and ammonium phosphate.

40. The immunogenic composition of claim 39, comprising each of NaCl, Na2HPO4· 2H2O, KH2PO4, sucrose, L-Arginine monohydrochloride, DMPC, poloxamer 188, Vitamin E, glycerol, and ammonium phosphate.

41. The immunogenic composition of claim 39 or 40, comprising about 25 mg / mL to about 40 mg / mL squalene.

42. The immunogenic of claim 41, comprising about 29.4 mg / mL squalene.

43. The immunogenic of claim 41, comprising about 37.6 mg / mL squalene 44. The immunogenic composition of any one of claims 39-42, comprising about 115 mcg / mL of a VZV gE antigen.

45. The immunogenic composition of claim 39 or 44, comprising about 3 mg to about 4 mg of NaCl; about 0.3 mg to about 0.5 mg Na2HPO4· 2H2O; about 0.04 mg to about 0.07 mg KH2PO4; 35 mg to about 45 mg sucrose; about 5 mg to about 7 mg L-Arginine monohydrochloride; about 5 mg / mL to about 9 mg / mL DMPC; about 200 mcg / mL to about 450 mcg / mL poloxamer 188; about 50 mcg / mL to about 250 mcg / mL Vitamin E; about 15 mg / mL to about 30 mg / mL glycerol; about 1.5 mg / mL to about 3.5 mg / mL of ammonium phosphate, monobasic; and about 0.05 mg / mL to about 2.5 mg / mL ammonium phosphate, dibasic.

46. The immunogenic composition of claim 39 or 45, comprising about 3.46 mg / mL of NaCl; about 0.385 mg / mL Na2HPO4· 2H2O; about 0.056 mg / mL KH2PO4; about 38.5 mg / mL sucrose; about 5.76 mg / mL L-Arginine monohydrochloride; about 6.58 mg / mL DMPC;Docket No.: CURV-010 / 02WO 340277-2148 about 310 mcg / mL poloxamer 188; about 173 mcg / mL Vitamin E; about 19.9 mg / mL glycerol; about 2.34 mg / mL ammonium phosphate, monobasic; and about 0.144 mg / mL ammonium phosphate, dibasic.

47. The immunogenic composition of claim 39 or 45, comprising about 3.46 mg / mL of NaCl; about 0.385 mg / mL Na2HPO4· 2H2O; about 0.056 mg / mL KH2PO4; about 38.5 mg / mL sucrose; about 5.76 mg / mL L-Arginine monohydrochloride; about 8.4 mg / mL DMPC; about 310 mcg / mL poloxamer 188; about 221 mcg / mL Vitamin E; about 25.4 mg / mL glycerol; about 2.99 mg / mL ammonium phosphate, monobasic; and about 0.192 mg / mL ammonium phosphate, dibasic.

48. The immunogenic composition of any one of claims 39-47, wherein the SLA adjuvant has the following structure:Docket No.: CURV-010 / 02WO 340277-214849. A dose of an immunogenic composition comprising: about 100, 101, 102, or 103 mcg of a Varicella-zoster virus gE glycoprotein (VZV- gE) antigen comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 2; about 15 mcg of an SLA adjuvant; about 26.5 mg of squalene; about 3.12 mg of NaCl; about 0.346 mg Na2HPO4· 2H2O; about 0.050 mg KH2PO4; about 34.6 mg sucrose; about 5.19 mg L-Arginine monohydrochloride; about 5.92 mg DMPC; about 277 mcg poloxamer 188; about 156 mcg Vitamin E; about 17.9 mg glycerol; about 2.1 mg ammonium phosphate, monobasic; and about 0.13 mg ammonium phosphate, dibasic.

50. A dose of an immunogenic composition comprising:Docket No.: CURV-010 / 02WO 340277-2148 about 100, 101, 102, or 103 mcg of a Varicella-zoster virus gE glycoprotein (VZV- gE) antigen comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 2; about 19.9 mcg of an SLA adjuvant; about 33.8 mg of squalene; about 3.12 mg of NaCl; about 0.346 mg Na2HPO4· 2H2O; about 0.050 mg KH2PO4; about 34.6 mg sucrose; about 5.19 mg L-Arginine monohydrochloride; about 7.56 mg DMPC; about 355 mcg poloxamer 188; about 199 mcg Vitamin E; about 22.9 mg glycerol; about 2.69 mg ammonium phosphate, monobasic; and about 0.17 mg ammonium phosphate, dibasic.

51. A pre-filled syringe comprising the dose of any one of claims 49 or 50.

52. A method of preventing Herpes Zoster in a subject in need thereof, comprising administration of the dose of any one of claims 49 or 50.

53. The method of claim 52, further comprising administration of a second dose according to any one of claims 49 or 50.

54. The method of claim 53, wherein the first and second dose are administered at least 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, or 8 weeks apart.

55. The method of any one of claims 51 -54, wherein the subject has not previously received a dose of Shingrix®.

56. The method of any one of claims 51 - 54, wherein the subject has previously received one or more doses of Shingrix®.

57. The method of any one of claims 51 - 56, wherein the administration is subcutaneous or intramuscular.

58. A stock solution comprising a second-generation lipid adjuvant (SLA), 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC), vitamin E, squalene, glycerol, poloxamer 188, ammonium phosphate, monobasic, and / or ammonium phosphate, dibasic; wherein the SLA comprises the structure set forth in Formula I or Formula IIDocket No.: CURV-010 / 02WO 340277-214859. The stock solution of claim 58, wherein the stock solution comprises: about 100 to about 200 mcg / ml SLA; about 25 to about 75 mg / mL DMPC; about 0.5 to 2.5 mg / mL vitamin E; about 150 to 300 mg / mL squalene; about 150 to 250 mg / mL glycerol; about 1.5 to 3.5 mg / mL poloxamer 188; about 15 to 25 mg / mL ammonium phosphate, monobasic; and / or about 0.5 to 2.5 mg / mL ammonium phosphate, dibasic.

60. The stock solution of claim 58 or 59, wherein the stock solution comprises: 150 mcg / ml SLA; 57 mg / mL DMPC; 1.5 mg / mL vitamin E; 255 mg / mL squalene; 172.5 mg / mL glycerol; 2.7 mg / mL poloxamer 188; 20.25 mg / mL ammonium phosphate, monobasic; and 1.275 mg / mL ammonium phosphate, dibasic.

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