Pharmaceutical compositions for respiratory infections and uses thereof

Abstract

The present invention relates to a pharmaceutical composition comprising the lipopeptide adjuvant Cys-Dipalmitoyl-Ser-Lys-Lys-Lys-Lys-PEG2-NH2 (otherwise referred to as dipalmitoyl- S-glyceryl-cysteine or Pam2Cys), an antigen, and mannitol, for the treatment and / or prevention of respiratory infections. Disclosed herein, is NoVCoV, a nasal dry powder vaccine that provides a novel and stable alternative to traditional liquid vaccines. This formulation is not only effective for preventing and / or treating COVID-19 but is also adaptable for addressing other respiratory infections.

Description

Pharmaceutical Compositions for Respiratory Infections and Uses ThereofCROSS REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of Australian Provisional Application No.2025900305 filed on 5 February 2025, the entire contents of which is incorporated by reference herein.FIELD OF THE INVENTION

[0002] The present invention relates to the field of vaccines, more specifically, to the formulation and preparation of a dry nasal powder vaccine for the treatment and / or prevention of respiratory pathogens, including, but not limited to coronavirus disease 2019 (COVID-19) and other respiratory infections. However, it will be appreciated that the invention is not limited to this particular field of use.BACKGROUND OF THE INVENTION

[0003] The following discussion of the prior art is provided to place the invention in an appropriate technical context and enable the advantages of it to be more fully understood. It should be appreciated, however, that any discussion of the prior art throughout the specification should not be considered as an express or implied admission that such prior art is widely known or forms part of the common general knowledge in the field.

[0004] Severe acute respiratory syndrome coronavirus 2, also known as 2019-nCov-2 or SARS-CoV-2, is the virus responsible for COVID-19. COVID-19 presents with respiratory symptoms such as dry cough, sputum production, and difficulty breathing, often accompanied by fever. In severe cases, it can lead to complications such as acute respiratory distress syndrome, heart failure, and arrhythmias. The Delta variant, a mutated strain of the virus, is characterized by a shorter incubation period and increased transmissibility compared to earlier variants. This variant has been linked to more severe disease outcomes and has posed significant challenges to public health measures and existing vaccination strategies.

[0005] Despite advancements in vaccines and therapies targeting SARS-CoV-2, the emergence of variants like Delta highlights the need for innovative approaches to enhance prevention, treatment, and management. Specifically, there is a demand for solutions addressing the heightened transmissibility and potential for immune evasion exhibited by such variants.

[0006] Several vaccine candidates against coronaviruses including SARS-CoV-2 have been evaluated in animal models, including whole-inactivated, subunit, DNA, mRNA, viral-vectored,and live attenuated vaccines. These candidates primarily target the spike (S) protein, the antigen required for viral entry into cells. Neutralizing antibodies against the spike protein are critical for protection. However, T-cell-mediated immune responses also play a pivotal role in defending against lethal coronavirus challenges. An ideal coronavirus vaccine should stimulate humoral and cell-mediated immunity in the mucosa to effectively prevent infection.

[0007] It is an object of the present invention to overcome or ameliorate one or more the disadvantages of the prior art, or at least to provide a useful alternative.

[0008] It one aspect, the present invention relates to a vaccine composition that elicits a comprehensive immune response, combining mucosal, humoral, and T-cell-mediated immunity at the site of infection, and is effective against SARS-CoV-2 and its variants, including those with enhanced transmissibility or immune escape characteristics.

[0009] It another aspect, the present invention relates to a recombinant protein and a nasal spray vaccine against the COVID- 19 mutant strain Delta, and its preparation method and application.

[0010] Although the invention will be described with reference to specific examples it will be appreciated by those skilled in the art that the invention may be embodied in many other forms.SUMMARY OF THE INVENTION

[0011] According to a first aspect, the present invention provides a pharmaceutical composition for nasal administration comprising:a) a lipopeptide adjuvant Cys-Dipalmitoyl-Ser-Lys-Lys-Lys-Lys-PEG2-NH2 (otherwise referred to as dipalmitoyl-S-glyceryl-cysteine or Pam2Cys);b) an antigen; andc) mannitol,wherein the composition is formulated as a dry power with more than about 90% of the particles being larger than about 10 pm.

[0012] In other embodiments, the composition is formulated as a liquid, nose drops, spray, or suitable for inhalation, as powder, or as emulsion.

[0013] In other embodiments, the composition is formulated as a dry powder with more than about 70%, 75%, 80%, 85%, 90%, 95% or about 100% of the particles being larger than about 10 pm.

[0014] In other embodiments, the particle median diameter is about 10 pm, 20 pm, 30 pm, 40 pm, 50 pm, 60 pm, 70 pm, 80 pm, 90 pm, 100 pm or about 150 pm.

[0015] In an embodiment, the lipopeptide adjuvant dipalmitoyl-S-glyceryl-cysteine is termed Pam2Cys.

[0016] In other embodiments, the lipopeptide adjuvant dipalmitoyl-S-glyceryl-cysteine is Pam3Cys, FSL-1, PEG-R4-Pam-2-Cys, MALP-2, lipopeitochoic acid, Porin, lipomannan, Lysophosphatidylserine, Lipophosphoglycan (LPG) and Glycophosphatidylinositol (GPI).

[0017] In other embodiments, composition is formulated to comprise a sugar alcohol mannitol, xylitol, sorbitol, erythritol containing between 4 and 8 carbons.

[0018] In an embodiment, the antigen comprises a Spike (S) receptor binding domain, protein or an immunogenic fragment or immunogenic variant thereof.

[0019] In an embodiment, the antigen is derived from the SARS-CoV-2.

[0020] In other embodiments, the antigen is derived from coronavirus, rhinovirus, influenza, respiratory syncytial virus, adenovirus, parainfluenza and metapneumovirus, and Epstein- Barr virus, and bacterial infections such as Mycobacterium tuberculosis.

[0021] In an embodiment, the SARS-CoV-2 spike is a delta-variant spike protein or other variant spike proteins.

[0022] In an embodiment, the composition comprises:a) about 0.3% w / w of Pam2Cys;b) about 0.3% w / w of a delta-variant spike protein; andc) about 99.3% w / w of mannitol.

[0023] In other embodiments, the amount of Pam2Cys in the composition is about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or about 1% w / w.

[0024] In other embodiments, the amount of delta-variant spike protein in the composition is about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or about 1% w / w.

[0025] In other embodiments, the amount of mannitol in the composition is about 99.8, 99.6, 99.2, 99.0, 98.8, 98.6, 98.4, 98.2, or about 98.0% w / w.

[0026] In an embodiment, the composition is frozen at about -80°C for about 2 hours to facilitate freeze-drying and stabilisation of the delta-variant spike protein.

[0027] In other embodiments, the composition is frozen at about -100°C, -80°C, -60°C, -40°C, -20°C or about 0°C.

[0028] In an embodiment, the composition is freeze-dried to produce said dry powder suitable for nasal administration.

[0029] In other embodiments, the composition is suitable for nasal, oral, intranasal, sublingual, and inhalation administration.

[0030] In an embodiment, the dry powder comprises a water content of less than about 1% w / w.

[0031] In other embodiments, the water content of the dry powder is about 0, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.11%, 0.12%, 0.13%, 0.14%, 0.15%, 0.16%, 0.17%, 0.18%, 0.19% or about 0.2% w / w.

[0032] In an embodiment, the dry powder is stored at about 4°C to stabilise the composition prior to nasal administration.

[0033] In other embodiments, the dry powder is stored at about -30°C, -28°C, -26°C, -24°, -22°C, -20°C, -18°C, -16°C, -14°C, -12°C, -10°C, -8°C, -6°C, -4°C, -2°C, 0°C, 2°C, 4°C, 6°C, 8°C 10°C, 12°C, 14°C, 16°C, 18°C, 20°C, 22°C, 24°C, 26°C, 28°C, or about 30°C.

[0034] In one embodiment, the pharmaceutical composition described herein comprises an excipient selected from a non-reducing sugar, an amino acid, an antioxidant, and any combinations thereof. For example, the non-reducing sugar may be trehalose, sucrose, or raffinose, the animo acid may be glycine, arginine, or histidine, and the antioxidant may be methionine, glutathione, sodium ascorbate, or a-tocopherol acetate.

[0035] According to a second aspect, the present invention provides a method of treating and / or preventing a respiratory infection in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising:a) a lipopeptide adjuvant Cys-Dipalmitoyl-Ser-Lys-Lys-Lys-Lys-PEG2-NH2 (otherwise referred to as dipalmitoyl-S-glyceryl-cysteine or Pam2Cys);b) an antigen;c) and mannitol,wherein the composition is formulated as a dry power with more than about 90% of the particles being larger than about 10 pm.

[0036] In an embodiment, the lipopeptide adjuvant dipalmitoyl-S-glyceryl-cysteine is Pam2Cys.

[0037] In other embodiments, the lipopeptide adjuvant dipalmitoyl-S-glyceryl-cysteine is Pam3Cys, FSL-1, PEG-R4-Pam-2-Cys, MALP-2, lipopeitochoic acid, Porin, lipomannan, Lysophosphatidylserine, Lipophosphoglycan (LPG), or Glycophosphatidylinositol (GPI).

[0038] In other embodiments, the composition is formulated to comprise a sugar alcohol mannitol, xylitol, sorbitol, or erythritol containing between 4 and 8 carbons.

[0039] In an embodiment, the antigen comprises a Spike (S) receptor binding domain, protein or an immunogenic fragment or immunogenic variant thereof.

[0040] In an embodiment, the antigen is derived from SARS-CoV-2.

[0041] In an embodiment, the SARS-CoV-2 antigen is selected from alpha, beta, gamma, kappa or delta strains or other variants.

[0042] In an embodiment, the SARS-CoV-2 spike is a delta-variant spike protein.

[0043] In an embodiment, the composition is freeze-dried to produce said dry powder suitable for nasal administration.

[0044] In other embodiments, the water content of the dry powder is about 0, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.11%, 0.12%, 0.13%, 0.14%, 0.15%, 0.16%, 0.17%, 0.18%, 0.19% or about 0.2% w / w.

[0045] In an embodiment, the dry powder is stored at about 4°C to stabilise the composition prior to nasal administration.

[0046] In other embodiments, the composition is suitable for nasal, oral, intranasal, sublingual, and inhalation administration.

[0047] In other embodiments, the dry powder is stored at about -30°C, -28°C, -26°C, -24°, -22°C, -20°C, -18°C, -16°C, -14°C, -12°C, -10°C, -8°C, -6°C, -4°C, -2°C, 0°C, 2°C, 4°C, 6°C, 8°C 10°C, 12°C, 14°C, 16°C, 18°C, 20°C, 22°C, 24°C, 26°C, 28°C, or about 30°C.

[0048] In an embodiment, the respiratory infection is selected from the group consisting of coronavirus, rhinovirus, influenza, respiratory syncytial virus, adenovirus, parainfluenza and metapneumovirus, and Epstein-Barr virus, and bacterial infections such as Mycobacterium tuberculosis.

[0049] In an embodiment, the respiratory infection is coronavirus.

[0050] In an embodiment, the coronavirus infection is SARS-CoV-2.

[0051] In an embodiment, the SARS-CoV-2 antigen is selected from alpha, beta, gamma, kappa or delta strains or other variants.

[0052] In an embodiment, the SARS-CoV-2 is the delta strain.

[0053] In an embodiment, the composition upon administration induces spike-specific neutralising antibodies in the blood and T cells in the nasal passages and lungs of the subject.

[0054] In other embodiments, the spike-specific and neutralising antibodies are IgG and IgA and are present in the blood, the nasal secretions and in the bronchoalveolar lavage fluid (BALF).

[0055] In other embodiments, the spike-specific T cells are CD4+ T cells.

[0056] In other embodiments, the composition is suitable for nasal, oral, intranasal, sublingual, and inhalation administration.

[0057] In other embodiments, the subject is selected from the group comprising mammals, including but not limited to, murine, hamster, and primate species.

[0058] In one embodiment, the method comprises administering a pharmaceutical composition described herein comprising an excipient selected from a non-reducing sugar, an amino acid, an antioxidant, and any combinations thereof. For example, the non-reducing sugar may be trehalose, sucrose, or raffinose, the amino acid may be glycine, arginine, or histidine, and the antioxidant may be methionine, glutathione, sodium ascorbate, or a-tocopherol acetate.

[0059] According to a third aspect, the present invention provides use of a composition in the manufacture of a medicament for treating and / or preventing a respiratory infection in a subject in need thereof comprising:a) a lipopeptide adjuvant Cys-Dipalmitoyl-Ser-Lys-Lys-Lys-Lys-PEG2-NH2 (otherwise referred to as dipalmitoyl-S-glyceryl-cysteine or Pam2Cys);b) an antigen; andc) mannitol,wherein the composition is formulated as a dry power with more than about 90% of the particles being larger than about 10 pm.

[0060] In an embodiment, the lipopeptide adjuvant Cys-Dipalmitoyl-Ser-Lys-Lys-Lys-Lys-PEG2-NH2 (dipalmitoyl-S-glyceryl-cysteine) is Pam2Cys.

[0061] In other embodiments, the lipopeptide adjuvant dipalmitoyl-S-glyceryl-cysteine is Pam3Cys, FSL-1, PEG-R4-Pam-2-Cys, MALP-2, lipopeitochoic acid, Porin, lipomannan, Lysophosphatidylserine, Lipophosphoglycan (LPG), or Glycophosphatidylinositol (GPI).

[0062] In other embodiments, the composition is formulated to comprise a sugar alcohol, mannitol, xylitol, sorbitol, or erythritol containing between 4 and 8 carbons

[0063] In an embodiment, the antigen comprises a Spike (S) receptor binding domain, protein or an immunogenic fragment or immunogenic variant thereof.

[0064] In an embodiment, the antigen is derived from SARS-CoV-2.

[0065] In an embodiment, the SARS-CoV-2 antigen is selected from alpha, beta, gamma, kappa, or delta strains or other variants.

[0066] In an embodiment, the SARS-CoV-2 spike is a delta-variant spike protein.

[0067] In an embodiment, the composition is freeze-dried to produce said dry powder suitable for nasal administration.

[0068] In other embodiments, the composition is suitable for nasal, oral, intranasal, sublingual, and inhalation administration.

[0069] In other embodiments, the water content of the dry powder is about 0, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.11%, 0.12%, 0.13%, 0.14%, 0.15%, 0.16%, 0.17%, 0.18%, 0.19% or about 0.2% w / w.

[0070] In an embodiment, the dry powder is stored at about 4°C to stabilise the composition prior to nasal administration.

[0071] In other embodiments, the dry powder is stored at about -30°C, -28°C, -26°C, -24°, -22°C, -20°C, -18°C, -16°C, -14°C, -12°C, -10°C, -8°C, -6°C, -4°C, -2°C, 0°C, 2°C, 4°C, 6°C, 8°C 10°C, 12°C, 14°C, 16°C, 18°C, 20°C, 22°C, 24°C, 26°C, 28°C, or about 30°C. .

[0072] In an embodiment, the respiratory infection is selected from the group consisting of coronavirus, rhinovirus, influenza, respiratory syncytial virus, adenovirus, parainfluenza and metapneumovirus, and Epstein-Barr virus, and bacterial infections such as Mycobacterium tuberculosis.

[0073] In an embodiment, the respiratory infection is coronavirus.

[0074] In an embodiment, the coronavirus infection is SARS-CoV-2.

[0075] In an embodiment, the SARS-CoV-2 antigen is selected from alpha, beta, gamma, kappa or delta strains or other variants.

[0076] In an embodiment, SARS-CoV-2 is the delta strain.

[0077] In an embodiment, the composition upon administration induces spike-specific neutralising antibodies and T cells in the blood and in the nasal passages and lungs of the subject.

[0078] In other embodiments, the spike-specific and neutralising antibodies are IgG and IgA and are present in the blood, the nasal secretions and in the bronchoalveolar lavage fluid (BALF).

[0079] In other embodiments, the spike-specific T cells are CD4+ T cells.

[0080] In other embodiments, the composition is suitable for nasal, oral, intranasal, sublingual, and inhalation administration.

[0081] In other embodiments, the subject is selected from the group comprising: mammals, including but not limited to, murine, hamster, and primate species.

[0082] In one embodiment, the pharmaceutical composition used in the manufacture of a medicament comprises an excipient selected from a non-reducing sugar, an amino acid, an antioxidant, and any combinations thereof. For example, the non-reducing sugar may be trehalose, sucrose, or raffinose, the amino acid may be glycine, arginine, or histidine, and the antioxidant may be methionine, glutathione, sodium ascorbate, or a-tocopherol acetate.

[0083] According to a fourth aspect, the present invention provides a pharmaceutical composition for use in treating and / or preventing respiratory infection in a subject in need thereof comprising:a) a lipopeptide adjuvant Cys-Dipalmitoyl-Ser-Lys-Lys-Lys-Lys-PEG2-NH2 (otherwise referred to as dipalmitoyl-S-glyceryl-cysteine or Pam2Cys);b) an antigen;c) and mannitol,wherein the composition is formulated as a dry power with more than about 90% of the particles being larger than about 10 pm.

[0084] In an embodiment, the lipopeptide adjuvant dipalmitoyl-S-glyceryl-cysteine is Pam2Cys.

[0085] In other embodiments, the lipopeptide adjuvant dipalmitoyl-S-glyceryl-cysteine is Pam3Cys, FSL-1, PEG-R4-Pam-2-Cys, MALP-2, lipopeitochoic acid, Porin, lipomannan, Lysophosphatidylserine, Lipophosphoglycan (LPG), or Glycophosphatidylinositol (GPI).

[0086] In other embodiments, the composition is formulated to comprise a sugar alcohol, mannitol, xylitol, sorbitol, or erythritol containing 4 to 8 carbons

[0087] In an embodiment, the antigen comprises a Spike (S) receptor binding domain, protein or an immunogenic fragment or immunogenic variant thereof.

[0088] In an embodiment, the antigen is derived from SARS-CoV-2.

[0089] In an embodiment, the SARS-CoV-2 antigen is selected from alpha, beta, gamma, kappa or delta strains or other variants.

[0090] In an embodiment, the SARS-CoV-2 spike is a delta-variant spike protein.

[0091] In an embodiment, the composition is freeze-dried to produce said dry powder suitable for nasal administration.

[0092] In other embodiments, the water content of the dry powder is about 0, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.11%, 0.12%, 0.13%, 0.14%, 0.15%, 0.16%, 0.17%, 0.18%, 0.19% or about 0.2% w / w.

[0093] In an embodiment, the dry powder is stored at about 4°C to stabilise the composition prior to nasal administration.

[0094] In other embodiments, the composition is suitable for nasal, oral, intranasal, sublingual, and inhalation administration.

[0095] In other embodiments, the dry powder is stored at about -30°C, -28°C, -26°C, -24°, -22°C, -20°C, -18°C, -16°C, -14°C, -12°C, -10°C, -8°C, -6°C, -4°C, -2°C, 0°C, 2°C, 4°C, 6°C, 8°C 10°C, 12°C, 14°C, 16°C, 18°C, 20°C, 22°C, 24°C, 26°C, 28°C, or about 30°C.

[0096] In an embodiment, the respiratory infection is selected from the group consisting of: coronavirus, rhinovirus, influenza, respiratory syncytial virus, adenovirus, parainfluenza and metapneumovirus, Epstein-Barr virus and bacterial infections such as Mycobacterium tuberculosis.

[0097] In an embodiment, the respiratory infection is coronavirus.

[0098] In an embodiment, the coronavirus infection is SARS-CoV-2.

[0099] In an embodiment, the SARS-CoV-2 antigen is selected from alpha, beta, gamma, kappa or delta strains or variants.[000100] In an embodiment, SARS-CoV-2 is the delta strain.[000101] In an embodiment, the composition upon administration induces spike-specific neutralising antibodies in the blood and T cells in the nasal passages and lungs of the subject.[000102] In other embodiments, the spike-specific and neutralising antibodies are IgG and IgA and are present in the blood, the nasal secretions and in the bronchoalveolar lavage fluid (BALF).[000103] In other embodiments, the spike-specific T cells are CD4+ T cells.[000104] In other embodiments, the composition is suitable for nasal, oral, intranasal, sublingual, and inhalation administration.[000105] In other embodiments, the subject is selected from the group comprising: mammals, including but not limited to, murine, hamster, and primate species.[000106] In other embodiments, the subject is murine.[000107] In one embodiment, the pharmaceutical composition for use described herein comprises an excipient selected from a non-reducing sugar, an amino acid, an antioxidant, and any combinations thereof. For example, the non-reducing sugar may be trehalose, sucrose, or raffinose, the amino acid may be glycine, arginine, or histidine, and the antioxidant may be methionine, glutathione, sodium ascorbate, or a-tocopherol acetate.[000108] Without wishing to be bound by any theory, the use of the pharmaceutical composition as described herein may treat and / or prevent any respiratory infection in a subject.[000109] In one embodiment, the antigen is derived from the SARS-CoV-2, Influenza A (IAV), Respiratory Syncytial Virus (RSV), or Epstein-Barr Virus (EBV). In one embodiment, the antigen comprises a protein or an immunogenic fragment or immunogenic variant thereof derived from a virus. The virus may be a coronavirus, influenza, RSA, or EBV. In one embodiment, the antigen comprises Hemagglutinin (HA) or Neuraminidase (NA) of IAV. In one embodiment, the antigen comprises pre-Fusion (F) protein or Glycoprotein (G) of RSV. In one embodiment, the antigen comprises a glycoprotein of EBV including, but not limited to, Glycoprotein B (gB), gp350, gHgL, and gHgLgp42.[000110] The skilled person will appreciate that the present invention may provide one or more significant advantages and improvements in the field and / or in view of the prior art. For example, these advantages include:(i) The ability to stabilise vaccine compositions preferably as a dry powder;(ii) The ability to avoid degradation of said composition;(iii) The ability to prevent respiratory infections in subjects; and / or(iv) The ability to induce protective immunity.DEFINITIONS[000111] In describing and claiming the present invention, the following terminology will be used in accordance with the definitions set out below. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments of the invention only and is not intended to be limiting.[000112] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one having ordinary skill in the art to which the invention pertains.[000113] Unless the context clearly requires otherwise, throughout the description and the claims, the terms “comprise”, “'comprising”, and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense of “including, but not limited to”. For example, a composition, mixture, process or method that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, mixture, process or method.[000114] The transitional phrase "consisting of’ excludes any element, step, or ingredient not specified. If in the claim, such would close the claim to the inclusion of materials other than those recited except for impurities ordinarily associated therewith. When the phrase "consisting of' appears in a clause of the body of a claim, rather than immediately following the preamble, it limits only the element set forth in that clause; other elements are not excluded from the claim as a whole.[000115] The transitional phrase "consisting essentially of" is used to define a composition, process or method that includes materials, steps, features, components, or elements, in addition to those literally disclosed, provided that these additional materials, steps, features, components, or elements do not materially affect the basic and novel characteristic(s) of the claimed invention. The term "consisting essentially of" occupies a middle ground between "comprising" and "consisting of".[000116] Where the applicant has defined an invention or a portion thereof with an open-ended term such as "comprising", it should be readily understood that (unless otherwise stated) the description should be interpreted to also describe such an invention using the terms "consisting essentially of" or "consisting of." In other words, with respect to the terms “comprising”, “consisting of”, and “consisting essentially of’, where one of these three terms is used herein, the presently disclosed and claimed subject matter may include the use of either of the other two terms. Thus, in some embodiments not otherwise explicitly recited, any instance of “comprising” may be replaced by “consisting of” or, alternatively, by “consisting essentially of”.[000117] While reference may be made in this disclosure to the invention comprising a combination of a plurality of elements, it is also understood that this invention is regarded to comprise combinations which omit or exclude one or more of such elements, even if this omission or exclusion of an element or elements is not expressly stated herein, unless it is expressly stated herein that an element is essential to the applicant's combination and cannot be omitted. It is further understood that the related prior art may include elements from which this invention may be distinguished by negative claim limitations, even without any express statement of such negative limitations herein. It is to be understood, between the positive statements of applicant's invention expressly stated herein, and the prior art and knowledge of the prior art by those of ordinary skill which is incorporated herein even if not expressly reproduced here for reasons of economy, that any and all such negative claim limitations supported by the prior art are also considered to be within the scope of this disclosure and its associated claims, even absent any express statement herein about any particular negative claim limitations.[000118] As used herein, with reference to numbers in a range of numerals, the terms "about," "approximately" and "substantially" are understood to refer to the range of -10% to +10% of the referenced number, preferably -5% to +5% of the referenced number, more preferably -1 % to + 1 % of the referenced number, most preferably -0 .1 % to +0 .1 % of the referenced number. Moreover, with reference to numerical ranges, these terms should be construed as providing support for a claim directed to any number or subset of numbers in that range. For example, a disclosure of from 1 to 10 should be construed as supporting a range of from 1 to 8, from 3 to 7, from 1 to 9, from 3.6 to 4.6, from 3.5 to 9.9, from 8 to 10, and so forth.[000119] The terms “preferred” and “preferably” refer to embodiments of the invention that may afford certain benefits, under certain circumstances. However, other embodiments may also be preferred, under the same or other circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not useful, and is not intended to exclude other embodiments from the scope of the invention.[000120] The complete disclosures of the patents, patent documents and publications cited herein are incorporated by reference in their entirety as if each were individually incorporated.[000121] Unless expressly stated to the contrary, "or" refers to an inclusive or and not to an exclusive or. For example, a condition A or B is satisfied by any one of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present).[000122] The term "and / or" used in the context of "X and / or Y" should be interpreted as "X," or "Y," or "X and Y." Similarly, "at least one of X or Y" should be interpreted as "X," or "Y," or "both X and Y."[000123] The indefinite articles "a" and "an" preceding an element or component of the invention are intended to be non-restrictive regarding the number of instances (i.e. , occurrences) of the element or component. Therefore "a" or "an" should be read to include one or at least one, and the singular word form of the element or component also includes the plural unless the number is obviously meant to be singular.[000124] As used herein, wt.% refers to the weight of a particular component relative to total weight of the referenced composition.[000125] As used herein, w / w % refers to the weight over weight of the referenced dry powder composition.[000126] As used herein, w / v % refers to the weight over volume of the referenced composition.[000127] It will be understood that use of the term “between” herein when referring to a range of numerical values encompasses the numerical values at each endpoint of the range. For example, a temperature of between 80°C and 150°C is inclusive of a temperature of 80°C and a temperature of 150°C.[000128] Various features of the embodiments of the invention disclosed herein are, for brevity, described in the context of a single embodiment, but may also be provided separately or in any suitable sub-combination. All combinations of the embodiments are specifically embraced by the illustrative embodiments disclosed herein just as if each and every combination was individually and explicitly disclosed. In addition, all sub-combinations listed in the embodiments describing such variables are also specifically embraced by the present compositions and are disclosed herein just as if each and every such sub-combination was individually and explicitly disclosed herein.[000129] In the foregoing paragraphs, various ratios of components have been disclosed. It will be appreciated that these ratios of components can be combined in any disclosed combination. For example, the ratio of A:B (which may be between about 100:1 and 1:100 or any range therein), may be combined with the ratio of C:D (which may be between about 50:1 and 1:50 or any range therein), and may be combined with the ratio of E:F (which may be between about 10:1 and about 1:10 or any range therein).[000130] As used herein, the term a "therapeutically effective amount" is at least the minimum concentration or amount required to affect a measurable improvement of a particular disease or condition, or induce a desired response such as an immune response. A therapeutically effective amount herein may vary according to factors such as the disease state, age, sex and weight of the patient. A therapeutically effective amount is also one in which any toxic or detrimental effects are outweighed by the therapeutically beneficial effects.[000131] As used herein, the term “pharmaceutical composition” or “compositions” hereinafter refers to preparations that are in such a form as to permit the biological activity of the active agents to be unequivocally effective, and which contain no additional components which are toxic as administered to the patients.[000132] As used herein, the symbol “A” refers to the delta variant of SARS-CoV-2.[000133] As used herein, “NoVCoV” refers to a nasal subunit vaccine platform used to treat and / or prevent COVID-19 and / or other respiratory infections.[000134] As used herein, “Cys-Dipalmitoyl-Ser-Lys-Lys-Lys-Lys-PEG2-NH2” is a lipopeptide adjuvant and refers to dipalmitoyl-S-glyceryl-cysteine or Pam2Cys.BRIEF DESCRIPTION OF THE DRAWINGS[000135] The aspects described above, as well as other apparent aspects, advantages, and objectives of the present invention are apparent from the detailed description below in combination with the drawing, in which:[000136] Figures 1 and 1A relates to graphical representations of nose-only vaccination generating comparable humoral immune responses to nose-lung delivery in both the circulation and mucosa. C57BL / 6 mice were immunized with 5 pg Pam2Cys and 6 pg ancestral spike protein formulated in phosphate buffered saline (PBS) via nose-only or nose-lung delivery as per the schedule outlined in (A). Serum was collected one week after the final boost and tissues were harvested at seven weeks. Serum was analysed at each time point (B, C) for anti-spike antibody titres. Nasal wash and BALF collected seven weeks after vaccination were also examined for anti-spike antibodies (D, E). Ratio of total lgG1 / lgG2c in the serum and BALF at seven weeks post-boost are shown in (F). Serum (G, H) and BALF (I) was also analysed for neutralizing antibodies (Nab) using pseudovirus assay. Data is pooled from two independent experiments with n=10 per group showing mean + / - SEM. (B-F) were analysed using a 2-way ANOVA with Tukey post- hoc test where p < 0.0332(*).[000137] Figure 2 relates to graphical representations of nose-only vaccination promoting the retention of tissue-resident memory T cells in the nasal turbinates and NALT. C57BL / 6 mice were immunized with 5 pg Pam2Cys and 6 pg ancestral spike protein via nose-only or nose-lung delivery as per the schedule outlined in Figure 1A, with tissues harvested at seven weeks postboost. Antigen-specific T cells were recalled from the NALT, nasal turbinates, lungs and cervical lymph node (cLN) of mice (A-D). Tissue-resident memory T cells (TRM-like) were defined as CD4+CD69+CD44+CD62L- or CD8+CD69+CD44+CD103+CD62L- in the lungs, nasal turbinates and NALT (E-G). For (B-F) data is pooled from two independent experiments with n=10 per group and data was analysed for differences using a 2-way ANOVA with Tukey post-hoc test where p< 0.0332(*). For (E-G), data is representative of a single experiment with n=5 per group. Differences were calculated using Kruskal-Wallis test with Dunn’s post-hoc test where p < 0.0332(*). All graphs show mean + / - SEM.[000138] Figures 3, 3A and 3B relates to graphical representations of nose-only immunisation with Pam2Cys ASpike generating T cell responses in the upper respiratory tract. C57BL / 6 mice were immunized with 5 pg Pam2Cys and 6 pg delta spike protein either twice subcutaneously followed by nose-only or a full schedule of nose-only delivery as outlined in (A). TRM-like CD4+ T cells (defined as CD4+CD44+CD69+CD62L-) in the nasal turbinates shown in (B). Representative FACS plots of the data shown in (B) is depicted in (C). Single cell suspensions were restimulated with delta spike protein and intracellular cytokine staining of CD4+ T cells from the NALT, nasal turbinates, lungs and cLN are shown (D-G). Data is pooled from the two independent experiments with n=9-10 per group and depicts + / - SEM. Differences were calculated in (B) using a one-way ANOVA with post-hoc Tukey test where p < 0.0332(*). Difference in (D-G) were calculated using 2-way ANOVA with post-hoc Tukey test where p < 0.0332(*).[000139] Figures 4, 4A and 4B presents graphical data demonstrating that nose-only vaccination or boosting with Pam2Cys AS spike generates robust humoral immune responses in both the circulation and mucosa. C57BL / 6 mice were immunized with 5 pg Pam2Cys and 6 pg delta spike protein via nose-only or nose-lung delivery, following the schedule outlined in panel (A). Serum was collected one week after the final boost, and tissues were harvested at eight weeks. Serum anti-spike antibody titres were analyzed at each time point (A-H). Additionally, sera, BALF, and nasal wash samples were tested for pseudovirus neutralization (l-L) and live-virus neutralization (M-O). Data are pooled from two independent experiments with n=10 per group and are presented as mean ± SEM. Panels (A-H) were analyzed for differences using a one-way ANOVA with post-hoc Dunn’s test, while panels (l-O) were analyzed using a 2-way ANOVA with Tukey post-hoc test, where * indicates p < 0.0332.[000140] Figures 5 and 5A relates to graphical representations of nose-only vaccination or boosting with Pam2Cys ASpike generating robust humoral immune responses in both the circulation of hACE2-K18 mice and is protective against SARS-CoV-2. hACE2-K18 mice were immunized with 5 pg Pam2Cys and 6 pg delta spike protein as per the schedule outlined in (A), except mice receiving subcutaneous (SC) vaccinations that received a SC boost contain 3 pg Pam2Cys and 6 pg delta spike protein. Serum was collected 7 weeks after the final boost. (B) Serum anti-spike antibody titres. Serum was also analysed for neutralizing antibodies (Nab) using live virus neutralization assay (C). 8 weeks after challenged animals were infected with 1000 PFU delta variant SARS-CoV-2 and assessed for weight loss (C) and clinical scoring (E). The viral titre of brains and lungs collected 6 days post-infection are depicted in (F,G). Inflammatory cells in thelungs after challenge are shown in (H-K). (B,C) were analysed using a 2-way ANOVA with Tukey post-hoc test where p < 0.0332(*). Differences in (D) were examined using a one-way ANOVA with post-hoc Tukey test. (F-K) were analysed using a Kruskal-Wallis with Dunn’s post-hoc test. For all graphs, p < 0.0332(*). Data is representative of one experiment with n=6 per group showing mean + / - SEM.[000141] Figure 6 provides visual and graphical representations showing that the NoVCoV powder is stable and suitable for URT delivery. (A) Aptar Unidose Device used to deliver the nasal powder vaccine to patients. (B) SDS-PAGE gels representing content uniformity (CU) of deltavariant spike protein in the vaccine powder samples, PL, protein ladder, one band detected in standards samples representative of delta-variant spike protein stability during process. (C) Particle size distribution of aerosolized vaccine powder actuated from Aptar Unidose Device. (D) stability of Pam2Cys adjuvant and (E) delta-spike protein in freeze-dried NoVCoV formulation (approximately 60 pg Pam2Cys and 60 pg Spike protein in 20 mg freeze-dried powder) packaged in Unidose device versus the 60 pg Pam2Cys and 60 pg Spike protein in 300 pL PBS stored in syringes (Vaccine liquid) after being stored in the fridge (4° Celsius).[000142] Figure 7 provides graphical representation of TLR2 activation and its un-impairment by freeze-drying of Pam2Cys. The adjuvant activity of Pam2Cys after freeze-drying in NoVCoV vaccine formulation was tested by addition of either Pam2Cys alone or after NoVCoV to HEK293T-TLR2 reporter cells that secrete IL-8 after TLR2 activation. A range of concentrations of either Pam2Cys alone of NoVCoV vaccine was added and cells were incubated overnight. The next day, IL-8 in cell culture supernatants was measured by ELISA.[000143] Figure 8 relates to schematical and graphical representations of reconstituted NoVCoV powder vaccine eliciting SARS-CoV-2 specific immune responses in the upper respiratory tract. (A) Experiment outline. Mice (n=10 per group) were immunised nose-only with the vaccines described and immune responses analysed one week after the final immunization. (B,C) Spike -specific CD4+ T cell responses in the nasal-associated lymphoid tissue and nasal turbinates. (D,E) Spike-specific antibody titres in the bronchoalveolar lavage fluid (BALF) and serum 1-week post-immunisation. (F) Neutralising antibody titres in the serum 1-week postimmunisation. (B,C) show mean + / - SEM of n=6 mice per group, analysed using 1-way ANOVA with post-hoc Tukey test. (D-F) show mean + / - SEM of n=10 mice per group.[000144] Figure 9 relates to schematical and graphical representations of the reconstituted dry powder vaccine providing complete protection in hACE2-K18 mice against challenge with delta variant SARS-CoV-2. (A) Experiment outline. Mice were immunized nose-only with the vaccines described and challenged with delta variant SARS-CoV-26 weeks post-immunisation. (B) Deltavariant spike-specific antibody titres and (C) neutralizing antibody tires in the serum 5 weeks postimmunisation. (D) Weight curves and (E) clinical scores of animals after infection with SARS-CoV-2. (F-H) Viral titres in the bronchoalveolar lavage (BALF), lungs and brain after SARS-CoV-2 challenge. Data shows mean + / - SEM of n=6 mice per group. Data in (C) was analysed using 1-way ANOVA with post-hoc Tukey test and (D) was analysed using 2-way ANOVA with post-hoc Tukey test.[000145] Figure 10 provides visual and graphical representations showing that the NoVCoV powder vaccine active components are stable over time. Freeze-dried NoVCoV formulation (approximately 60 pg Pam2Cys and 60 pg Spike protein in 20 mg freeze-dried powder) was prepared, packaged into Aptar Unidose devices that were sealed individually in foil packets also containing an oxygen scavenger and silicone bead desiccant pouch. (A) Stability of Pam2Cys adjuvant and delta-spike protein after vaccine was stored in the fridge (4° Celsius) or at room temperature (25° Celsius) for up to 6 months, as determined by quantitative HPLC. (B) Graphical representation of Pam2Cys stability in vaccine stored for 3 months at various temperatures, as shown by lack of degradation products detectable by HPLC. (C) TLR2 activation and its unimpairment by storage of Pam2Cys in vaccine powder at various temperatures, for 3 and 6 months. The adjuvant activity of Pam2Cys after freeze-drying and storage in NoVCoV vaccine formulation was tested by comparison to Pam2Cys alone, using HEK293T-TLR2 reporter cells that secrete IL-8 after TLR2 activation. An equivalent of 1 ug / ml Pam2Cys for all conditions was added and cells were incubated overnight. The next day, IL-8 in cell culture supernatants was measured by ELISA.[000146] Figure 11 relates to schematical and graphical representations of reconstituted NoVCoV powder vaccine, that has been stored for up to 6 months at varying temperatures, eliciting SARS-CoV-2 specific immune responses systemically and in the respiratory tract. Freeze-dried NoVCoV formulation (approximately 60 pg Pam2Cys and 60 pg Spike protein in 20 mg freeze-dried powder) was prepared, packaged into Aptar Unidose devices that were sealed individually in foil packets also containing an oxygen scavenger and silicone bead desiccant pouch. (A) Experiment outline. Mice (n= 3-5 per group) were immunised nose-only with 2mg of the vaccines described and immune responses analysed one week after the final immunization. Powder vaccine stored at -30, 4 or 25 degrees Celsius, was compared to freshly prepared liquid version of the vaccine at equivalent dosage to establish if freeze drying or storage altered immunogenicity. Spike-specific IgG and IgA antibody titres were quantitated by ELISA in the (B) serum, (C) bronchoalveolar lavage fluid (BALF) and (D) nasal wash 1-week post-immunisation. (B,C,D) show mean + / - SEM of n= 3-5 mice per group, analysed using Kruskal-Wallis ANOVA with uncorrected Dunn’s test for multiple comparisons.[000147] Figure 12 relates to schematical and graphical representation of the reconstituted dry powder vaccine providing robust protection in Syrian Hamsters against challenge with delta variant of SARS-CoV-2. (A) Experimental outline. Hamsters were immunized nose-only with 12g Pam2Cys and 12 pg SARS-CoV-2 delta protein in 4 mg mannitol or Placebo (mannitol only) as described in (A) and challenged with delta variant SARS-CoV-2 3 weeks post-immunisation. (B) Live virus titres in the lungs, bronchoalveolar lavage fluid (BALF), nasal turbinates and nasal wash. (C,D) Delta-variant spike-specific IgG antibody titres in plasma and (E) nasal wash. (F) Delta-variant spike-specific neutralising antibody titres in nasal wash, (G) plasma and (H) BALF. Data shows mean + / - SEM of n= 7 Syrian hamsters per group. Data in (B) was analysed using Student’s t-test, data in (C-E) was analysed using a Mann Whitney test and data in (F-H) was analysed using a Two-way ANOVA followed by Sidak’s multiple comparisons test, * p<0.05.[000148] Figure 13 relates to schematical and graphical representation of nose-lung or nose only immunisation with Pam2Cys and RSV pre-fusion F protein. Balb / c mice were immunized with 3 pg Pam2Cys and 5 pg RSV pre-fusion F protein to the nose-lung (i.n) or nose-only (n.o) as outlined in (A). RSV pre-fusion F protein specific antibody titres in (B) serum, (C) nasal wash and (D) bronchoalveolar lavage fluid (BALF), 1 week post final immunization, quantitated by ELISA. Single cell suspensions were restimulated with RSV pre-fusion F and intracellular cytokines produced by RSV-specific CD4+ T-cells in the (E) lung, (F) nasal tissue, (G) nasal associated lymphoid tissue (NALT), (H) mediastinal lymph node (MLN) and (I) cervical lymph nodes (cLN) are shown, quantitated by flow cytometry. Data shows mean + / - SEM of n= 5 Balb / c mice per group. Statistical difference was calculated in (B-D) using a Mann Whitney test, and in (E-l) using a Two-way ANOVA followed by an Uncorrected Fisher’s LSD with single pooled variance, p-values shown.[000149] Figure 14 relates to schematical and graphical representation of nose-lung or nose only immunisation with Pam2Cys and Influenza A HA protein. C57BI / 6 mice were immunized with 5 pg Pam2Cys and 5 pg HA to the nose-lung (i.n) or nose-only (n.o) as outlined in (A). HA specific antibody titres in (B) serum, (C) nasal wash and (D) BALF, 1 week post final immunization, quantitated by ELISA. Single cell suspensions were restimulated with HA and intracellular cytokines produced by lAV-specific CD4+ T-cells in the (E) lung and (F) mediastinal lymph node (MLN), and lAV-specific CD8+ T-cells in (G) MLN are shown, quantitated by flow cytometry. Data shows mean + / - SEM of n= 5 C57BI6 mice per group. Statistical difference was calculated in (B-D) using a Mann Whitney test, and in (E-G) using a Two-way ANOVA followed by an Uncorrected Fisher’s LSD with single pooled variance, p-values shown.[000150] Figure 15 relates to schematical and graphical representation of nose-lung immunisation with Pam2Cys and EBV proteins, gp350, gHgL and gB. Balb / c mice were immunized with 3 pg Pam2Cys and 5 pg gp350 protein, or 5 pg gHgL protein, or 5 pg gB protein to the nose-lung (i.n) as outlined in (A). EBV protein specific antibody titres in (B) serum and (C) BALF 2 weeks post final immunization, quantitated by ELISA. Single cell suspensions were restimulated with corresponding EBV proteins and intracellular cytokine staining of EBV-specificCD4+ and CD8+ T-cells in the (D) lung, (E) nasal associated lymphoid tissue (NALT) are shown, quantitated by flow cytometry. Data shows mean + / - SEM of n= 2-3 Balb / c mice per group. Statistical difference was calculated in (B-C) using a Mann Whitney test, and in (D-E) using a Two-way ANOVA followed by an Uncorrected Fisher’s LSD with single pooled variance, p-values shown.[000151] While specific embodiments are illustrated in the figures, with the understanding that the disclosure is intended to be illustrative, these embodiments are not intended to limit the invention described and illustrated herein.DETAILED DESCRIPTION[000152] The skilled addressee will understand that the invention comprises the embodiments and features disclosed herein as well as all combinations and / or permutations of the disclosed embodiments and features.[000153] In an aspect, the present invention provides a pharmaceutical composition for nasal administration comprising:a) a lipopeptide adjuvant Cys-Dipalmitoyl-Ser-Lys-Lys-Lys-Lys-PEG2-NH2 (otherwise referred to as dipalmitoyl-S-glyceryl-cysteine or Pam2Cys);b) an antigen; andc) mannitol,wherein the composition is formulated as a dry power with more than about 90% of the particles being larger than about 10 pm. In an embodiment, the composition is freeze-dried to produce said dry powder suitable for nasal administration.[000154] In other aspects, the invention provides methods and / or uses of the composition in vaccinating a subject against, inducing or enhancing an immune response against, treating or preventing, and / or reducing the symptoms of a respiratory infection. In other aspects, the disclosure provides methods and / or uses of the composition in vaccinating a subject against, inducing or enhancing an immune response against, treating or preventing, and / or reducing respiratory infections. In other embodiments, the respiratory infection is coronavirus.[000155] Headings are included herein for reference and to aid in locating certain sections. These headings are not intended to limit the scope of the concepts described therein under, and these concepts may have applicability in other sections throughout the entire specification.Respiratory Infections[000156] Respiratory infection are a group of diseases that affect the respiratory system, including the nose, sinuses, throat, airways, and lungs. They can be caused by variouspathogens, such as viruses, bacteria, and fungi, with common examples including influenza (e.g., influenza A or influenza B), respiratory syncytial virus, the common cold, pneumonia, and bronchitis. Symptoms typically range from mild, such as a runny nose and sore throat, to severe, such as difficulty breathing, fever, and chest pain. Respiratory infections can spread through airborne droplets, direct contact, or contaminated surfaces, making prevention strategies like good hygiene, vaccination, and avoiding close contact with infected individuals essential. While most cases resolve without complications, vulnerable populations, such as young children, the elderly, and those with underlying health conditions, may face serious health risks.[000157] Respiratory infections can be caused by a variety of viruses and bacteria each with distinct characteristics and associated diseases. These include the coronavirus, which has caused global outbreaks such as the COVID-19 pandemic, and the rhinovirus, the primary cause of the common cold. Other viruses that commonly affect the respiratory system include influenza, responsible for seasonal flu outbreaks, and respiratory syncytial virus (RSV), which poses a serious risk to young children and the elderly. Adenovirus, parainfluenza, metapneumovirus, and Epstein-Barr virus also contribute to respiratory infections, leading to conditions ranging from mild congestion to severe respiratory distress. These viruses are primarily transmitted through airborne droplets, and individuals in vulnerable populations, such as the very young, elderly, and those with compromised immune systems, are at higher risk for complications. Effective prevention strategies, including vaccination and proper hygiene, are critical in controlling the spread of these viral respiratory infections.Coronavirus[000158] The term "coronavirus" or "CoV" encompasses any virus in the coronavirus family, including but not limited to SARS-CoV-2, MERS-CoV, SARS-CoV, and other endemic coronaviruses such as HCoV-NL63, HCoV-229E, HCoV-OC43, and HKU1. SARS-CoV-2 specifically refers to the novel coronavirus that caused the major outbreak in Wuhan, China, and the resulting disease, COVID-19 (also herein referred to as COVID or COVID-19 disease), has subsequently spread worldwide.[000159] The subfamily Coronavirinae is further subdivided into four genera, namely alpha-, beta-, gamma-, and delta- coronavirus (a-CoV, p-CoV, y-CoV, and b-CoV). Viruses having the potential to infect humans are placed under the genus a-CoV and p-CoV (SARS-CoV & MERS-CoV), whereas viruses of y-CoV and b-CoV genera are mostly known to infect avians and pigs. The novel coronavirus, SARS-CoV-2 falls under the genus p-CoV, as it shares 88% sequence identity with SARS-CoV-like coronaviruses (derived from bat) but is only 79% identical to SARS-CoV and 50% identical to MERS-CoV. Thus, it can be deduced by its genome identity that the immediate host of this virus could be a bat, which then transmitted it to some unknown intermediate host that acted as a source for the transmission of the virus to humans.[000160] Evidence suggests that this virus spreads when an infected person coughs small droplets - packed with the virus - into the air. These can be breathed in, or cause an infection if one touches a surface they have landed on, then one’s eyes, nose or mouth. Though the symptoms of SARS-CoV-2 virus infection may be mild, and include typically fever and cough, it can also be asymptomatic or in the other extreme it can be severe or fatal, i.e. lethal. The key symptoms are usually high temperature, cough and breathing difficulties. Although there are meanwhile specific treatments and vaccines available for COVID, it still presents a substantial public health threat. Furthermore, various escape mutants have emerged (e.g. alpha, beta, delta and / or omicron and further future emerging strains may occur) which further worsen the situation and thus this unfortunate development needs to be addressed as well.[000161] The virus utilizes its spike protein to bind to human host cell receptors, primarily angiotensin-converting enzyme 2 (ACE2). Furthermore, the spike protein is cleaved by TMPRSS2, which activates it and facilitates the fusion of the viral membrane with the host cell membrane, enabling viral entry.SARS-CoV-2 Variants[000162] At present, according to the genealogy information of the new coronavirus published in the GISAID database, there are more than 700 mutations in the world, of which there are 8 mutants with strong transmission ability and wide distribution, namely: Alpha (B.1.1.7 mutant in the UK), Beta (South Africa B.1.351 mutant), Gamma (Brazil P.1 mutant), American B.1.2 mutant, Italian B.1 mutant, Eta (Nigerian B.1.525 mutant), Delta and currently prevailing dominant mutants Omicron.[000163] Alpha mutants have 9 defined mutations on the S protein. Studies have shown that the neutralization ability of the Alpha mutant pseudovirus by the serum of the Moderna mRNA vaccine and Novavax recombinant protein vaccine was not significantly different from that of the non-mutant. Phase 3 clinical data of the Novavax recombinant protein vaccine showed that the protective efficacy against the new coronavirus was 90%, while the protective efficacy against the Alpha mutant was 85%. Taken together, the protective efficacy of these vaccines against Alpha mutants may remain unchanged.[000164] Beta mutants have 10 defined mutations on the S protein. Studies have shown that its E484K mutation can significantly improve the ability of live viruses and pseudoviruses to resist monoclonal neutralizing antibodies and vaccine serum. In addition, Moderna's data showed that the neutralization effect of vaccine sera against Beta mutants decreased by more than 7-fold, and Pfizer's data also showed a significant decrease in neutralization. The results of the Phase III clinical trial of the Novavax recombinant protein vaccine showed that the efficacy against the Beta mutant was less than 50%. In conclusion, the emergence and prevalence of Beta mutants andmutants with similar characteristics to Beta mutants pose a huge challenge to the existing antiepidemic strategies.[000165] Gamma mutants, with 11 defined mutations on the S protein, have similar characteristics to Alpha and Beta mutants, including E484K, N501 Y mutations, so it is reasonable to speculate that they may have immune escape.[000166] The Delta variant (also known as B.1.617.2) is characterized by several mutations in the spike protein, namely mutation sits L425R and T478k, which may enhance its ability to bind to human ACE2 receptors, leading to increased transmissibility compared to earlier strains of the virus. Additionally, some of these mutations have been associated with partial resistance to neutralizing antibodies, potentially reducing the effectiveness of certain vaccines and treatments. This variant is associated with more severe disease outcomes, particularly in unvaccinated populations, and has prompted ongoing research into updated vaccines and therapeutic strategies to address the unique challenges posed by the Delta strain.Vaccines for Respiratory Infections[000167] Existing vaccines for viral respiratory infections have been pivotal in reducing the burden of diseases caused by respiratory viruses, including but not limited to, influenza, respiratory syncytial virus (RSV), and coronaviruses. Vaccines for these infections are designed to stimulate an immune response that targets specific viral proteins, typically the spike or surface proteins, to prevent viral entry into host cells and reduce the severity of disease upon infection.[000168] One of the most common vaccines is the influenza vaccine, which is designed to protect against the seasonal flu, caused by influenza viruses. These vaccines typically include inactivated virus strains or subunits of the virus, such as the hemagglutinin (HA) and neuraminidase (NA) proteins, which are critical for viral entry and replication. The flu vaccine is updated annually to address the antigenic changes in circulating strains, a necessity due to the virus’s tendency to rapidly mutate. Despite its broad use, the influenza vaccine's effectiveness can vary, and breakthrough infections may occur, particularly in individuals with compromised immune systems or in years when the virus undergoes significant antigenic drift.[000169] The current influenza vaccine formulations in Australia are delivered intramuscularly and consist of either adjuvanted or unadjuvanted influenza virus proteins. Live-attenuated influenza vaccines have been approved for intranasal delivery in several countries, including Russia, the USA, Canada, the EU, the UK, India, and China. However, such vaccines are in liquid formulation, and are typically less stable than dry powders.[000170] Vaccines for respiratory syncytial virus (RSV) and parainfluenza have also been under development for many years, with varying degrees of success. RSV is particularly concerning dueto its ability to cause severe infections in infants, a high-risk group, yet no vaccine is currently available to protect them against the virus. Meanwhile, adenovirus-based vaccines and other viral vectors have shown promising outcomes in the prevention of respiratory viral infections, demonstrated in both clinical trials and real-world applications.Vaccines for SARS-CoV-2[000171] The development of vaccines for respiratory viruses, particularly the novel coronavirus, has marked significant progress in the field of vaccinology. The COVID-19 vaccines, including mRNA-based vaccines (Pfizer-BioNTech, Moderna) and adenoviral vector vaccines (AstraZeneca), were developed in record time to address the global pandemic caused by SARS-CoV-2. These vaccines utilize novel technologies, with mRNA vaccines instructing cells to produce the spike protein of the virus to elicit an immune response, while adenoviral vector vaccines use a harmless virus to deliver the spike protein gene into cells. These vaccines have shown high efficacy in preventing severe illness, hospitalization, and death, and they have led to a major reduction in the global burden of COVID- 19. However, they are less effective at preventing infection in the nose and subsequent transmission.[000172] Such technologies include currently available injected COVID- 19 vaccines in Australia and internationally, such as the mRNA vaccines Comirnaty (Pfizer / BioNTech) and Spikevax (Moderna), which are considered the standard of care for COVID-19 vaccination. Mucosal vaccines approved for SARS-CoV-2 include iNCOVACC (Bharat Biotech) in India, Convidecia Air (CanSino Biologies) in China, and Razi Cov Pars (Razi Vaccine and Serum Research Institute) in Iran.[000173] These mucosal vaccines are liquid formulations, generally less stable than dry powders, and most utilize viral vectors that are unsuitable for immunocompromised populations. Unlike subunit vaccines such as NoVCoV, live-attenuated vaccines are not safe for immunocompromised individuals. Regarding intranasal Pam2Cys use, INNA-051, a product under development, contains a similar active ingredient to the adjuvant in NoVCoV. While INNA-051 is designed for prophylactic use against SARS-CoV-2 or influenza, it does not contain an antigenic component and solely relies on the activation of innate immune cells.[000174] Despite the success of these vaccines, challenges remain, including the need for updated vaccines to address emerging variants, such as the Delta and Omicron strains of SARS-CoV-2, and the variability in protection across different populations. Ongoing research aims to improve the breadth and durability of vaccines, especially those that can provide broader protection against a range of respiratory viruses.SARS-CoV-2 Pathogenesis[000175] Coronavirus virions are generally spherical, with diameters ranging from 80 to 200 nm. A key characteristic of these viruses is the club-shaped spike proteins that extend from their surface, resembling a solar corona, which is how they earned their name. Encased within the viral envelope is the nucleocapsid, which exhibits helical symmetry. This helical arrangement is uncommon in positive-sense RNA viruses but more frequently found in negative-sense RNA viruses. SARS-CoV-2, MERS-CoV, and SARS-CoV are examples of coronaviruses belonging to this family.[000176] All coronaviruses initiate entry inside the target cell by engaging the host receptor with the S glycoprotein present on their surface so as to gain entry inside the target cell. The region of S (Spike) protein containing the RBD (Receptor Binding Domain) is present on the S1 subunit. In a few coronaviruses, RBD is present at the N-terminus region of S1, whereas in SARS-CoV, it is situated at the C-terminus region. The fusogenic activity of virus-cell membrane is governed by two tandem domains, heptad repeats (HR1,2) that are present on the S2 region of S protein. Initially, it was believed that SARS-CoV enters the target cell merely by virtue of cell membrane integration of virus particle and host cell membrane. Later, it was discovered that an essential proteolytic cleavage event takes place in the S protein at the S2 position of SARS-CoV that results in membrane fusion and facilitates virus entry inside the cell.[000177] The path followed by SARS-CoV-2 to reach the lungs is via the naso-oral cavity. Once the virus is inhaled, it enters the epithelial cells of the nasal cavity by engagement of ACE2 receptor with the viral RBD and initiates its replication.[000178] This initial asymptomatic phase lasts for about 1-2 days, during which the virus multiplies in the upper respiratory tract, where no major hindrance is caused by the innate immune cells. Within 2-14 days of initial encounter, the common symptoms of COVID-19 start to appear, which are similar to those of SARS and MERS, i.e. , fever, dry cough, pharyngitis, shortness of breath, joint pain, and tiredness. Numerous problems arise during this phase of the disease, including nosocomial and fomite transmission of infection, which enhances the chances of community spread.Immune Response to SARS-CoV-2[000179] Once the virus gains access inside the target cell, the host immune system recognises the whole virus or its surface epitopes, eliciting the innate or adaptive immune response. Pathogen recognition receptors (PRRs) present on immune cells, mainly Toll-like receptors 3, 7, and 8, are the first to identify the virus, which leads to enhanced interferon (IFN) production.[000180] The function of host innate immune cells is impaired during SARS-CoV and MERS-CoV infection by their non-structural proteins, which affects the overall cytokine production. Humoral response against SARS-CoV-2 has been found to be similar to that against other coronavirus infections, involving the characteristic IgG, IgM, and IgA production.[000181] At the onset of SARS-CoV infection, B cells elicit an early response against the N protein, while antibodies against S protein could be detected after 4-8 days from the appearance of initial symptoms. Although N protein is smaller than S protein, it is highly immunogenic, and the absence of glycosylation sites on it results in N-specific neutralizing antibody production at an early stage of acute infection. As such, various studies have shown a protective humoral response, with neutralizing IgG, IgA and IgM antibodies targeting the N and S-RBD proteins of SARS-CoV-2.[000182] During viral infection, T cells also recognise the viral antigens presented by MHC class I [MHC; Human Leukocyte Antigen (HLA) in humans], which in turn promotes the cytokine release and cytotoxic activity of CD8+ T cells. But in some other cases, MHC class II is also found to present SARS-CoV peptides to CD4+ T cells.Pharmaceutical Compositions[000183] The present invention relates to a pharmaceutical composition for nasal administration, specifically formulated as a dry powder. In one aspect, the composition comprises three components: (a) a lipopeptide adjuvant Cys-Dipalmitoyl-Ser-Lys-Lys-Lys-Lys-PEG2-NH2 (otherwise referred to as dipalmitoyl-S-glyceryl-cysteine or Pam2Cys), (b) an antigen, and (c) mannitol.[000184] Pharmaceutical compositions are typically formulated to be compatible with its intended route of administration. Exemplary routes of administration include parenteral, e.g., intravenous, intradermal, subcutaneous, oral (e.g., inhalation or through a feeding tube), transdermal (topical), transmucosal, and rectal administration. The term parenteral as used herein includes subcutaneous, intracutaneous, intravenous, intramuscular, intra-articular, intraarterial, intrasynovial, intrasternal, intrathecal, intralesional and intracranial injection or infusion techniques. In some examples, the combination described herein may be administered via a route selected from the group consisting of parenteral, oral, intranasal, sublingual, rectal, intramuscular, intravenous, subcutaneous, intradermal, intrathecal, intra-arterial, intraperitoneal, and inhalation administration.[000185] For preparation of the compositions as injectable solutions or suspensions, non-toxic parenterally acceptable diluents or carriers may be used such as Ringer's solution, isotonic saline, phosphate buffered saline, ethanol and 1,2 propylene glycol.Adjuvants[000186] Adjuvants are added in to pharmaceutical vaccine compositions to enhance the immunogenicity of the pharmaceutical composition.[000187] Suitable adjuvants in the composition include a range of molecules known in the art, particularly those that act as TLR2 agonists. More specifically, a preferred TLR2 agonist is Pam2-Cys, such as Pam2Cys-SK4-Peg2-NH2. Other examples of TLR2 agonists that can be used include Pam3Cys, FSL-1, PEG-R4-Pam-2-Cys, MALP-2, lipopeitochoic acid, Porin, lipomannan, Lysophosphatidylserine, Lipophosphoglycan (LPG), and Glycophosphatidylinositol (GPI).[000188] The lipopeptide adjuvant wherein a lipid moiety that is known to act as an adjuvant is combined with a peptide immunogen, may be capable of enhancing the immunogenicity of an otherwise weakly immunogenic peptide in the absence of an extrinsic adjuvant [Tan, ACL, et al., Mol Pharm 9, 2710, (2012), Ashhurst AS, et al., Nat Commun, 13(1), 6972, (2022), Jung et al., Angew Chem, Int Ed Engl 10, 872, (1985); Martinon et al., J Immunol 149, 3416, (1992); Toyokuni et al., J Am Chem Soc 116, 395, (1994); Deprez, et al., J Med Chem 38, 459, (1995); and Sauzet et al., Vaccine 13, 1339, (1995)]. Lipopeptides like dipalmitoyl-S-glyceryl-cysteine play a crucial role in stimulating the innate immune system, particularly by activating Toll-like receptors (TLRs) that trigger immune cell recruitment and cytokine production. The lipopeptide structure provides a means to increase the stability and bioavailability of the antigen while promoting effective delivery to the nasal mucosa. Dipalmitoyl-S-glyceryl-cysteine is particularly effective in stimulating both cellular and humoral immune responses, making it an ideal candidate for use in vaccines targeting respiratory pathogens.Antigens[000189] The composition includes an antigen that is responsible for stimulating the immune system to produce an immune response. The antigen can be any substance capable of eliciting an immune response, such as proteins, peptides, or inactivated or live-attenuated viruses, which are commonly used in vaccines. In the context of nasal administration, the antigen should be chosen based on its ability to activate immune cells in the nasal mucosa and induce a systemic immune response. The antigen may be derived from pathogens causing respiratory diseases, such as coronaviruses, influenza viruses, or bacterial pathogens, but it is not limited to any specific pathogen or disease.[000190] One of the most critical targets for vaccine development is the antigenic components of the virus, particularly the Spike (S) protein and Nucleocapsid (N) protein. These proteins, present in viruses such as coronaviruses, including SARS-CoV-2, are essential for the virus’sability to infect host cells and reproduce, and for eliciting an immune response that can potentially inhibit and / or neutralise the virus.[000191] The antigen may be formulated in various forms, including whole antigens, subunits, or viral vectors, and can be selected based on the particular infectious agent or condition targeted by the vaccine. In one aspect, the antigen is the delta spike protein of SARS-CoV-2. In one aspect, the antigen is the glycoprotein of Influenza A (IAV), for example, Hemagglutinin (HA) or Neuraminidase (NA). In one aspect, the antigen is the pre-Fusion (F) protein or the Glycoprotein (G) of Respiratory Syncytial Virus (RSV). In another aspect, the antigen is gB, gp350, gHgL, or gHgLgp42 of Epstein-Barr Virus (EBV).Excipients[000192] The inclusion of mannitol in the pharmaceutical composition is particularly advantageous for dry powder formulations intended for nasal administration. Mannitol provides superior stability to the dry powder by protecting the active ingredients, such as the lipopeptide adjuvant dipalmitoyl-S-glyceryl-cysteine and the antigen, from degradation. This stabilising effect is critical for maintaining the immunogenicity of the antigen and the efficacy of the adjuvant over extended storage periods. Additionally, mannitol acts as a bulking agent, ensuring the uniformity of the powder formulation and preventing aggregation of the particles during manufacturing and storage.[000193] Mannitol also contributes to the aerodynamic properties of the dry powder formulation. By optimising particle size distribution and enhancing flowability, mannitol ensures efficient delivery of the composition to the nasal mucosa. This localised delivery minimises systemic exposure while targeting the nasal-associated lymphoid tissue (NALT) to stimulate a robust immune response.[000194] In addition to mannitol, the composition may include other excipients that serve to improve the overall stability, dispersibility, and functionality of the formulation. Specifically, osmolytes such as xylitol, erythritol, and sorbitol are valuable additions due to their ability to enhance vaccine stabilisation. These compounds can help mitigate protein aggregation and degradation by maintaining hydration and stabilising the tertiary structure of protein antigens. This stabilization effect is crucial for preserving the integrity and biological activity of protein-based vaccines, especially during storage and transportation under suboptimal conditions. Incorporating these osmolytes has been shown to significantly extend the shelf life of vaccines, thereby increasing their efficacy and accessibility, particularly in regions where cold chain logistics are challenging. Preferably, the stabilising agent is mannitol.[000195] In one aspect, the invention relates to a pharmaceutical composition for nasal administration comprising an adjuvant (e.g., Pam2Cys), an antigen, and an excipient. The excipient may serve to improve the overall stability, dispersibility, and functionality of the composition. Exemplary excipients include, but are not limited to, lyoprotectants such as sugars and their corresponding sugar alcohols (e.g., mannitol), amino acids, antioxidants, and any combinations thereof. Preferably, the sugar is a non-reducing sugar. Examples of non-reducing sugars include non-reducing glycosides of polyhydroxy compounds selected from sugar alcohols and other straight chain polyalcohols. Non-reducing sugars include, but are not limited to, trehalose, sucrose, and raffinose. These can provide an amorphous protective matrix during freezing and drying, which improves the retention of protein structure, for example, a Spike's tertiary and secondary structure. Examples of amnio acids include glycine, arginine, and histidine. These can help mitigate pH shifts during freezing, suppress mannitol crystallisation, and reduce antigen aggregation. Examples of antioxidants include methionine, glutathione, sodium ascorbate, and a-tocopherol acetate. These may preserve adjuvant integrity over extended storage.[000196] The pharmaceutical composition as described herein may comprise an adjuvant, an antigen, mannitol, and an additional excipient. The pharmaceutical composition as described herein may also comprise an adjuvant, an antigen, and an excipient selected from a sugar or sugar alcohol, an amino acid, an antioxidant, and any combinations thereof.[000197] To improve stability of the pharmaceutical composition as described herein, excipients such as a sugar or sugar alcohol, an amino acid, an antioxidant, and any combinations thereof may be added to the composition prior to drying.Dry Powder[000198] The pharmaceutical composition is formulated, but not limited to, a dry powder. Other formulations of the pharmaceutical composition may include, but is not limited to, liquid inactivated vaccines, liquid live-attenuated vaccines, liquid nasal and / or mucosal vaccines. Preferably, the pharmaceutical composition is a dry powder, which may comprise 70%, 75%, 80%, 85%, 90%, 95% or about 100% of particles with a range varying from about 10 pm to 300 pm. Preferably, more than 90% of the particles have a diameter larger than approximately 10 pm. This particle size distribution is significant because it facilitates the effective deposition of the dry powder in the nasal cavity and ensures the particles are large enough to be retained in the nasal mucosa, where they can interact with immune cells. Particles larger than 10 pm are more likely to be deposited in the upper airways, which are crucial sites for immune activation in respiratory infections. This particle size range enhances the stability and controlled release of the active ingredients, improving both local and systemic immune responses.Subjects[000199] In other aspects, the disclosure provides methods and / or uses of the composition in vaccinating a subject against, inducing or enhancing an immune response against, treating or preventing, and / or reducing the symptoms of an influenza infection. In other embodiments, a subject may be selected from, but not limited to, the group consisting of: mammals, including but not limited to, murine, hamster, and primate species.Administration[000200] The intranasal compositions of the disclosure can be formulated, for example, in liquid form as nose drops, spray, or suitable for inhalation, as powder, as cream, or as emulsion. Nebulised or aerosolised intranasal vaccines may also be utilised. Administration of compositions to mucosa of the upper and / or lower respiratory tract via inhalation of mists, powders, or sprays, or by intranasal administration of nose drops, swabs, powders, sprays, mists, aerosols, and the like is also contemplated.[000201] In one embodiment, the compositions for intranasal administration are provided in a freeze-dried powder form. Powder vaccine formulations of compositions of the present disclosure provide a means of overcoming refrigerated storage and distribution requirements associated with liquid-based vaccine stability and delivery. Dry powder formulations offer the advantage of being more stable and also do not support microbial growth.[000202] The freeze-dried compositions may induce levels of cross- protective immunity similar to that of non-freeze-dried compositions. The compositions may be freeze-dried using any suitable technique known in the art. For example, liquid preparations of a first immunogen and an antigen from a virus may be frozen in dry ice, followed by desiccation in a Freeze-Dryer (Alpha 2-4 LSC plus Freeze Dryer (Martin Christ, Germany)) for a suitable time period (e.g. 24 hours).[000203] Preferred devices for intranasal administration of the composition are nasal spray devices (e.g. UniDose nasal device). Non-limiting examples of suitable devices are described, for example, in Bommer, (1999), “Advances in Nasal drug delivery Technology”, Pharmaceutical Technology Europe, p26-33.Dosages[000204] Results revealed a delivered dose between 90 - 102% of the nominal dose in the 10 devices, which passes USP 905 acceptable limit for nasal delivery powder and devices which ranges from 75 - 125% Each UniDose device contained 20 mg vaccine powder, containing a nominal dose of 60 pg Pam2Cys and 60 pg delta spike protein. Thus, the range of activeingredients that was delivered was between 54 g and 61.2 pg of each Pam2Cys and delta spike protein from each device.Advantages of NoVCoV[000205] The current COVID-19 vaccines do not effectively stimulate mucosal immune responses. While systemic immunity plays a crucial role in reducing disease severity, it is not sufficient to prevent infection or the spread of respiratory viruses. NoVCoV, a nasal vaccine, induces both humoral and cellular immune memory in the nasal passages and lungs, offering a significant advantage over the mRNA vaccines in use today.[000206] NoVCoV is also a subunit vaccine, which provides a safety advantage over mRNA and viral vectored vaccines, as well as live attenuated vaccines, especially when delivered through the respiratory route. mRNA and adenoviral-vectored vaccines carry small risks of cardiomyopathy and thrombocytosis, respectively, while live attenuated vaccines are unsuitable for immunocompromised individuals due to safety concerns. Most of the currently approved mucosal COVID- 19 vaccines rely on viral vectors, as there is a lack of effective mucosal adjuvants for nasal subunit vaccines. The only nasal influenza vaccine is a live attenuated virus, which is also unsuitable for high-risk groups. Therefore, NoVCoV stands out in the mucosal vaccine market as a subunit vaccine that is safe for diverse populations while still inducing effective local immune responses.[000207] In addition, the inventor’s studies have demonstrated that nasal Pam2Cys in powder form, when combined with spike protein antigen, is effective. This formulation could potentially be adapted for other pathogens by simply altering the vaccine antigen. Similar adjuvanted subunit vaccines, such as GlaxoSmithKline’s AS04, which is used in the Fendrix hepatitis B vaccine and the Cervarix human papillomavirus vaccine, set a precedent for such adaptations. Therefore, the NoVCoV platform has the flexibility to induce protective immune responses against a wide range of mucosal pathogens.[000208] One of NoVCoV's key advantages is that it is a nasal vaccine formulated as a dry powder, pre-packaged in its delivery device. Currently, there are no dry powder nasal vaccines approved worldwide. Nasal vaccines generally enjoy higher acceptance rates among populations hesitant about needle injections, making NoVCoV an appealing option for booster doses, especially for individuals who have already received multiple SARS-CoV-2 vaccinations. Furthermore, dry powder vaccines are more stable than liquid forms and, unlike mRNA vaccines, do not require ultra-cold storage at -30°C or -80°C, reducing production and distribution costs. This makes NoVCoV more accessible to broader populations, including those in developing countries and rural areas.[000209] NoVCoV may provide superior stability at room temperature compared to -30°C or 4°C storage for up to 1 month, 3 months, 6 months, or more. This provides a substantial practical advantage for a clinical product to reduce reliance on cold chain distribution and storage for vaccination programs.[000210] In contrast, liquid nasal sprays can be swallowed, leading to poor absorption in the nasal tissues. Dry powders, however, have been shown to stay longer on the mucosal surface, enhancing immune responses. NoVCoV has the potential to revolutionize the way vaccines are developed for respiratory pathogens, offering an affordable, accessible, and safe solution that can reach diverse populations and provide protection to vulnerable individuals.EXAMPLES[000211] The present invention will now be described with reference to the following examples which should be considered in all respects as illustrative and non-restrictive.EXAMPLE 1: Preparation of Cvs-Dipalmitoyl-Ser-Lvs-Lvs-Lvs-Lys-PEG2-NH2 adjuvant[000212] Synthesis of Pam2Cys-SK4-Peg2-NH2 adjuvant proceeded with the loading of Fmoc-Peg2-OH (166108-71-0) to rink amide resin. First, the Rink Amide resin was treated with piperidine in DMF (1:4, v / v) to remove the Fmoc group, then the resin was washed with DMF, CH2CI2 and DMF again. The resin was then treated with a solution of Fmoc-Peg2-OH, Oxyma and N,N'-Diisopropylcarbodiimide in DMF. The remaining Ser-Lys-Lys-Lys-Lys portion of the peptide was extended in the same manner, using Fmoc-Lys(Boc)-OH and Fmoc-Ser(tBu)-OH. The Pam2Cys unit was installed using a Fmoc-S-[(R)-2,3- bis(palmitoyloxy)propyl]-L-cysteine building block. The N-terminal Fmoc group was then liberated with piperidine in DMF (1:4, v / v,) and the resin was washed with DMF then CH2CI2. The peptide was then liberated from resin and its sidechain protecting groups with an acidolytic treatment with TFA / i- Pr3SiH / H2O (90:5:5, v / v / v). The crude residue was purified by reverse-phase HPLC, with the buffers of water (0.1% formic acid) and acetonitrile (0.1% formic acid). The HCI salt of Pam2Cys-SK4-Peg2-NH2 was formed through iterative freeze-drying following re-solubilisation in dilute aqueous HCI.EXAMPLE 2: Preparation of Dry Vaccine Powder[000213] Using sample container suitable for freeze-drying, mannitol pre-solution was prepared by adding about 900 mg of Mannitol powder and 4 mL of Milli- Q water followed by stirring for 2-3 minutes at 450 rpm to ensure complete dispersion of powder in the solution. An aqueous solution of Pam2Cys at concentration of 1 mg / mL prepared using Pam2Cys GLP powder (Sai Scientific, India) dissolved in Milli-Q water added to the mannitol pre-solution with continuous stirring. Afterwards, an aqueous solution of 1 mg / mL delta-Spike Protein in DPBS (Excellgene, Switzerland) was transferred to the above mixture with stirring till complete dissolution. The finalvaccine solution is composed of 9%w / v mannitol, 0.03%w / v delta-spike protein, and 0.03%w / v Pam2Cys. The sample container was capped and placed inside -80 °C freezer or under dry ice for about 2 hours to ensure complete freezing of the solution. The prepared frozen sample was transferred to the Alpha 2-4 LSC plus Freeze Dryer (Martin Christ, Germany) located at Ab Initio Pharma GMP facility. Using the programmed freeze dryer cycle in Table 1, the drying process of the frozen vaccine sample will commence and continue for 24 hours. After the freeze dryer cycle has been completed, dry samples were removed from the chamber and stored inside a desiccator with silica beads at - 80 ° C freezer until filling the Aptar Unidose devices with 20 mg of the vaccine powder and packaging them in aluminum bags.Table 1: Freeze dryer cycle conditions for producing NoVCoV vaccine powder.EXAMPLE 2: Nasal Delivery[000214] Vaccine powder loaded into a UniDose nasal device is efficiently actuated from the device. The physical characteristic of the powder produced is suitable for nasal delivery since over 90% of the particles are larger than 10 pm, thus restricting the vaccine to the upper respiratory tract (URT), and the powder contains minimal water content.EXAMPLE 3: Animal Studies[000215] To establish that vaccination with Pam2Cys and SARS-CoV-2 spike protein to the URT only is sufficient to generate mucosal immune responses in the nasal tissues, mice were first immunised using a liquid formulation of the vaccine (spike protein and Pam2Cys formulatedin PBS). For these studies, the vaccine adjuvant Pam2Cys-SK4-triethylene glycolate (Parr^Cys) was produced as previously described [Ashhurst et al (2022), “Mucosal TLR2-activating proteinbased vaccination induces potent pulmonary immunity and protection against SARS-CoV-2 in mice” Nature Communications 13(1):6972], For studies testing the efficacy of the dry powder vaccine, Pam2Cys was purchased from Sai Life Sciences (India). SARS-CoV-2 HexaPro ancestral spike protein was expressed in Expi293F cells. Delta-variant SARS-CoV-2 HexaPro spike protein was obtained from Excellgene (Switzerland). Female C57BL / 6 mice were randomly allocated to an experimental group and immunized with 5 pg Parr^Cys and 6 pg spike protein (ancestral or delta variant) for all experiments except where otherwise stated. All immunizations were performed while mice were anaesthetised under inhalational isofluorane (1 L / min O2 and 4% isofluorane). Subcutaneous injections were performed in a total volume of 200 pL Dulbecco’s phosphate buffered saline (PBS; Sigma Aldrich, MA, USA) in the back skin, URT / LRT immunizations were performed using a total volume of 30 pL, and URT immunizations in a total volume of 12 pLto the nares (6 pL each nostril). To test the dry powder vaccine, 1-2 mg of vaccine powder was resolubilized in 12 pL PBS and administered to the nares.[000216] For SARS-CoV-2 challenge experiments, hemizygous K18-hACE2 mice that express the human angiotensin converting enzyme 2 (hACE2; entry receptor for SARS-CoV-2) were immunized as described in the figure descriptions and then challenged with delta-variant SARS-CoV-2. Briefly, mice were anaesthetized using isoflurane prior to intranasal challenge with SARS-CoV-2 (1,000 PFU, delta variant B.1.617.2) in 30 pL total volume. Mice were weighed and monitored for clinical symptoms daily and were euthanized at day 6 post-infection. Viral loads were determined in the BALF, lungs, and brain by plaque assay, and total leukocytes in the BALF were enumerated with a total cell count using a hemocytometer, after which cells were deposited onto glass slides using a cytospin. Slides were then stained using a Quick Dip Stain Kit (Modified Giemsa Stain) protocol as per the manufacturer’s instructions (POCD Scientific, Australia) and differential cell counts obtained.[000217] During some experiments, blood was collected by tail vein for serum. At endpoint, mice were euthanized by asphyxiation with CO2, before samples (blood, nasal wash, BALF, lungs, cervical lymph nodes, nasal turbinates and NALT) were collected aseptically. Blood was obtained via the inferior vena cava / portal vein, allowed to clot, then centrifuged (2000 xg, 15 min) to enable collection of sera. The BALF was collected via tracheal intubation, inflation of the airways with 1 mL DPBS and collection of the resultant fluid. Any cells were then removed by centrifugation, and the BALF was immediately frozen at -30°C. Nasal wash was collected by flushing 300 pL DPBS through the nares via the trachea while the mouse was laid supine. For collecting lung tissue, any circulating blood was removed through perfusion with PBS and heparin (20 U / mL, Sigma) injected into the right atrium of the heart. For some experiments, the apical lobe was inflated with 10% neutral buffered formalin and stored at room temperature for future histological analysis. Theremaining lung lobes were diced and then digested for 45 min at 37 °C with collagenase type 4197 (50 U / mL, Sigma) and DNase I (13 g / mL, Sigma), before being filtered through a 70 pm sieve. Nasal turbinates were similarly digested and filtered through a 70 pm sieve. Cervical lymph nodes and NALT were passed through a 70 pm filter, and the cells pelleted by centrifugation. Lysis of erythrocytes was performed using ACK lysis buffer (Gibco, Thermo Fisher Scientific, MA, USA) where necessary, and then leukocytes enumerated using a Countess 3FL (Invitrogen, MA, USA) with Trypan Blue (0.4%; Invitrogen) exclusion. To determine antigen-specific T cell responses, cells were incubated in the presence of 5 pg / mL spike protein (either delta or ancestral variant depending on experiment) and spike peptide 538-546 at 5 pg / mL concentration (epitope previously identified to be recognised by CD8+T cells) for 4 hours at 37°C, before the addition of 10 pg / mL Brefeldin A (Sigma) and incubation overnight at 37°C. Samples were then stained with fluorochrome-conjugated monoclonal antibodies and analysed on an LSRII-5L flow cytometer (Becton Dickinson, Sydney Cytometry Facility).[000218] Spike-specific antibody titres were determined by coating Corning 96-well Clear Flat Bottom Polystyrene High Bind Microplates (Corning, NY, USA) with 1 pg / mL spike protein (ancestral or delta) in carbonate coating buffer (0.05M pH 9.6 = 1.59 g / L Na2COs, 2.93 g / L NaHCCh), 70 pL per well, then incubating at 4°C overnight. Plates were then washed with PBS (POCD) and 0.05% Tween 20 (Sigma), before being blocked with 1% bovine serum albumin (BSA; Bovogen, Vic, Australia) in PBS for 1 hour at 37°C. Serum samples were serially diluted in 1% BSA / PBS then added to washed microplates and incubated for 1 hour at 37°C. Secondary antibodies conjugated to HRP were then added diluted 1 in 2000 in 1% BSA / PBS and incubated for 30 minutes at 37°C. Antibodies used were anti-mouse IgG is Novex (#A16090, Life Technologies, CA, USA), anti-mouse lgG1 (#115-035-205, Jackson ImmunoResearch, PA, USA), anti-mouse lgG2c Jackson (#115-035-208, ImmunoResearch), and anti-mouse IgA (#626720, Invitrogen). Plates were then washed and TMB substrate (Sigma) was added and allowed to develop for approximately 2 minutes before the reaction was stopped by the addition of an equal volume of 2M HCI (Sigma). Absorbances were read at 450 nm (570 nm reference) on a Tecan plate reader. Pseudovirus assays were performed as follows. Briefly, HEK293T cells transduced to express human ACE-2 were added to a 384-well plate (poly-D-lysine coated; PerkinElmer, MA, USA) and incubated at 37°C. The next day, serially diluted serum, BALF or nasal wash from immunized animals was incubated with pseudoviruses expressing spike protein from ancestral, delta or omicron BA4 / 5. The pseudoviruses were then added to ACE-2-HEK293T cells, and level of infection was measured by fluorescence using a Phoenix high throughput microscope (Sydney Cytometry Facility). The proportion of infected cells was enumerated using Harmony® high-content analysis software (Perkin Elmer). NAb titres were determined as the dilution required for >50% inhibition of infection (EC50) compared to the infection levels of adjuvant-only controls, estimated by sigmoidal curve and interpolation (GraphPad Prism 10).EXAMPLE 4: Powder Vaccine Stability StudyStability assessment of active components of dry powder vaccine[000219] Freeze-dried NoVCoV formulation (approximately 60 g Pam2Cys and 60 pg Spike protein in 20 mg mannitol as freeze-dried powder) was prepared, packaged into Aptar Unidose devices that were sealed individually in foil packets also containing an oxygen scavenger and silicone bead desiccant pouch. Stability of Pam2Cys adjuvant and delta-spike protein was determined after vaccine was stored in the fridge (4° Celsius) or at room temperature (25° Celsius) for up to 6 months. Vaccine was actuated from devices and active components quantitated against standard calibration curve by quantitative HPLC. Activity of Pam2Cys to activate TLR2 was evaluated using HEK293T-TLR2 reporter cells that secrete IL-8 after TLR2 activation. The adjuvant activity of Pam2Cys after freeze-drying and storage in NoVCoV vaccine formulation was tested by comparison to Pam2Cys alone. IL-8 in cell culture supernatants was measured by ELISA.Immunogenicity study[000220] For immunogenicity studies testing the efficacy of the dry powder vaccine after storage at various temperatures, powder vaccine was formulated and packaged as in examples above, then stored at -30 °C, 4 °C or 25 °C for up to 6 months. Female C57BI / 6 mice were randomly allocated to an experimental group. All immunizations were performed while mice were anaesthetised under inhalational isofluorane (1 L / min O2 and 4% isofluorane). Mice received URT immunizations in a total volume of 12 pL to the nares (6ul each nostril). To test the dry powder vaccine, 2 mg of vaccine powder (2 mg mannitol, 6 pg Parr^Cys and 6 pg delta spike) was resolubilized in 12 pL PBS and administered to the nares. This was compared to freshly prepared soluble liquid vaccine with equivalent active components as a control to determine in powder formulation or storage altered immunogenicity.[000221] During some experiments, blood was collected by tail vein for serum. At endpoint, mice were euthanized by asphyxiation with CO2, before samples (blood, nasal wash, BALF) were collected aseptically. Blood was obtained via the inferior vena cava / portal vein, allowed to clot, then centrifuged (2000 xg, 15 min) to enable collection of sera. The BALF was collected via tracheal intubation, inflation of the airways with 1 mL DPBS and collection of the resultant fluid. Any cells were then removed by centrifugation, and the BALF was immediately frozen at -30°C. Nasal wash was collected by flushing 300 pL DPBS through the nares via the trachea while the mouse was laid supine. Spike-specific antibody titres were determined by coating Corning 96-well Clear Flat Bottom Polystyrene High Bind Microplates (Corning, NY, USA) with 1 pg / mL delta spike protein in carbonate coating buffer (0.05M pH 9.6 = 1.59 g / L Na2COs, 2.93 g / L NaHCCh), 70 pL per well, then incubating at 4°C overnight. Plates were then washed with PBS (POCD) and0.05% Tween 20 (Sigma), before being blocked with 1% bovine serum albumin (BSA; Bovogen, Vic, Australia) in PBS for 1 hour at 37°C. Serum samples were serially diluted in 1% BSA / PBS then added to washed microplates and incubated for 1 hour at 37°C. Secondary antibodies conjugated to HRP or biotin were then added diluted 1 in 2000 (IgG) or 1:4,000 (IgA) in 1% BSA / PBS and incubated for 30 minutes at 37°C. Antibodies used were anti-mouse IgG is Novex (#A16090, Life Technologies, CA, USA) and anti-mouse IgA-biotin (#AB97233, Abeam). For IgA plates, SA-HRP was added at 1:10,000 (Pierce High Sensitivity #21130). Plates were then washed and TMB substrate (Sigma) was added and allowed to develop for approximately 2 minutes before the reaction was stopped by the addition of an equal volume of 2M HCI (Sigma). Absorbances were read at 450 nm (570 nm reference) on a Tecan plate reader.Protection from SARS-CoV-2 in Hamster model[000222] Efficacy of the powdered NoV CoV (nose-only vaccine for COVID-19) was established in a Syrian hamster model (contracted to the Institute Biological Sciences (ICB), UFMG, Brazil). Syrian hamsters (6 weeks old) were purchased from UFMG. The experiments were performed in the Animal Biosafety Level 3 (ABSL-3) facility at the Institute of Biological Sciences from UFMG. All animals were maintained with a 12 h light / dark cycle with humidity of 50-58% and temperature of 25 °C. The SARS-CoV-2 viral strain used in this study belonged to the lineage Delta. Viral stocks were propagated in Vero CCL81 in a humidified incubator at 37°C with 5% CO2 and monitored for cytopathic effects (CPE) daily up to 72 h. Viruses were titrated in Vero CCL81 cells by plaque-forming units (PFU) assay, and viral aliquots were kept at -80 °C until further use. The hamsters were immunized with an intranasal administration of 20 pL vehicle with 4 mg placebo (mannitol) or 4 mg vaccine (4 mg mannitol, 12 pg Pam2Cys, 12 pL delta-spike). On the 14th and 28th day after vaccination, all groups were boosted with the same dose of vehicle or vaccine. Blood samples were collected from all animals 1 day prior and 48th after immunization. At 49th post immunization, hamsters were challenged with 100 pL of saline or SARS-CoV-2 (3x104PFU, Delta variant) (Souza et al. 2023). Weight and clinical signs, including piloerection, hunched posture, and lethargy (0. Absent, 1. Mild, 2. Significantly present) were monitored during the experiment. The animals were euthanized 3 days post-challenge and blood, lungs, BAL, nasal turbinate and nasal wash were collected for further analysis. Bronchoalveolar lavage fluid (BAL) was collected by instilling 1 mL of phosphate-buffered saline (PBS) through a tracheal catheter, withdrawing and re-instilling the fluid twice more. This process was repeated, and the lavages were pooled. Nasal wash was collected instilling 400 pL of PBS into the nasal cavity of the hamsters. All surgery procedures were carried out under ketamine / xylazine anesthesia.[000223] Viral titration. To assess viral titters, a serial dilution of lungs, plasma, BALF, nasal wash and nasal turbinate homogenates of immunized hamsters was incubated in monolayers of Vero CCL81 cells (105cells / well) plated in 24-well plates for 1 h at 37 °C. Fresh semisolid mediumcontaining 1.5% carboxymethylcellulose (CMC) was added, and the culture was maintained for 72 h at 37 °C. Cells were fixed with 10% formaldehyde for 2 h at room temperature and then stained with crystal violet (0.4%). The virus titers were determined by plaque forming units (PFU) per milliliter or milligram.[000224] Plaque reduction neutralization test (PRNT). Plasma, BALF and Nasal wash samples were heat-inactivated by incubation at 56 °C for 20min in a dry bath. Serial dilutions of the samples were mixed with an equal amount of virus suspension containing 100 plaque-forming units (PFU) in 0.1 mL. After incubation at 37 °C for 1 h, each virus-diluted serum sample (0.1 mL) was inoculated into one well of a 24-well plate containing a confluent monolayer of 105Vero cells. After incubation at 37 °C for 1 h, fresh semisolid medium containing 1.5% carboxymethylcellulose (CMC) was added, and the culture was maintained for 72 h at 37 °C. Cells were fixed with 10% formaldehyde for 2 h at room temperature and then stained with crystal violet (0.4%), and plaques were counted. The antibody titer was determined as the serum dilution that inhibited 50% of the tested virus inoculum (PRNT50).[000225] Anti-SARS-CoV-2 IgG ELISA. To detect anti-SARS-CoV-2 IgG in hamster plasma, nasal wash and BAL samples, we performed an indirect ELISA. Briefly, 96-well plates were coated with inactivated delta SARS-CoV-2 antigen (1*105PFU / well) and incubated overnight at 4 °C. After washing with PBS-Tween 0.01%, plates were blocked with 1% BSA for 1 h at room temperature. Samples were serially diluted 1:10, 1:100, 1:1000, 1:5000 and 1:25000 in 0.1% BSA and added to the wells (100 pL / well), followed by incubation for 1 h at 37 °C under agitation. After washing, bound antibodies were detected using HRP-conjugated anti-hamster IgG (20 ng / well; Sigma Aldrich CAT SAB3700490). Plates were incubated for 1h at 37 °C, washed, and developed with OPD substrate supplemented with H2O2. The reaction was stopped with 1 M H2SO4, and absorbance was read at 490 nm in a plate reader. Results are shown as IgG titers, which were determined as the highest serum dilution yielding an absorbance value above the cut-off, defined as the mock mean absorbance plus two standard deviations.EXAMPLE 5: In-Vivo Testing for Influenza A (I AV), Respiratory Syncytial Virus (RSV), and Epstein-Barr Virus (EBV)[000226] To establish that vaccination with Pam2Cys and RSV pre-fusion F protein to the URT / LRT or URT only is sufficient to generate mucosal immune responses in the nasal tissues, mice were immunised using techniques as in example 3 (vaccine components were RSV prefusion F protein and Pam2Cys formulated in PBS). For these studies, the vaccine adjuvant Pam2Cys-SK4-triethylene glycolate (Pam2Cys) was produced as previously described (Ashhurst et al (2022), “Mucosal TLR2-activating protein-based vaccination induces potent pulmonary immunity and protection against SARS-CoV-2 in mice” Nature Communications 13(1):6972). RSV pre-fusion F protein was purchased from Sino Biological (USA). Female Balb / c mice wererandomly allocated to an experimental group and immunized with 3 pg Parr^Cys and 5 pg RSV pre-fusion F protein for all experiments except where otherwise stated. All immunizations were performed while mice were anaesthetised under inhalational isofluorane (1 L / min O2 and 4% isofluorane). URT / LRT immunizations were performed using a total volume of 30 pL, and URT immunizations in a total volume of 12 pL to the nares (6 pl each nostril).[000227] To establish that vaccination with Pam2Cys and IAV HA protein to the URT / LRT or URT only is sufficient to generate mucosal immune responses in the nasal tissues, mice were immunised using a liquid formulation of the vaccine (IAV HA protein and Pam2Cys formulated in PBS). For these studies, the vaccine adjuvant Pam2Cys-SK4-triethylene glycolate (Parr^Cys) was produced as previously described (Ashhurst et al (2022), “Mucosal TLR2-activating protein-based vaccination induces potent pulmonary immunity and protection against SARS-CoV-2 in mice” Nature Communications 13(1):6972). IAV HA protein was purchased from Sino Biological (USA). Female C57BI / 6 mice were randomly allocated to an experimental group and immunized with 5 pg Parr^Cys and 5 pg IAV HA protein for all experiments except where otherwise stated. All immunizations were performed while mice were anaesthetised under inhalational isofluorane (1 L / min O2 and 4% isofluorane). URT / LRT immunizations were performed using a total volume of 30 pL, and URT immunizations in a total volume of 12 pL to the nares (6 pL each nostril).[000228] To establish that vaccination with Pam2Cys and EBV gp350, or EBV gHgL, or EBV gB protein to the URT / LRT is sufficient to generate mucosal immune responses in the nasal tissues, mice were immunised using a liquid formulation of the vaccine (EBV gp350, or EBV gHgL, or EBV gB protein and Pam2Cys formulated in PBS). For these studies, the vaccine adjuvant Pam2Cys-SK4-triethylene glycolate (Parr^Cys) was produced as previously described (Ashhurst et al (2022), “Mucosal TLR2-activating protein-based vaccination induces potent pulmonary immunity and protection against SARS-CoV-2 in mice” Nature Communications 13(1 ):6972). EBV gp350, or EBV gHgL proteins were purchased from Sino Biological (USA). EBV gB protein was purchased from AcroBioSystems (USA). Female Balb / c mice were randomly allocated to an experimental group and immunized with 3 pg Pam2Cys and 5 pg EBV gp350, or 5 pg EBV gHgL, or 5 pg EBV gB protein for all experiments except where otherwise stated. All immunizations were performed while mice were anaesthetised under inhalational isofluorane (1 L / min O2 and 4% isofluorane). URT / LRT immunizations were performed using a total volume of 30 pL.[000229] Immunogenicity of RSV, IAV and EBV nasal vaccines were established using techniques as described in Examples 3 and 4, with modification to assess the antigen-specific T-cell and antibody responses against RSV, IAV or EBV as relevant.[000230] Although the invention has been described with reference to specific examples, it will be appreciated by those skilled in the art that the invention may be embodied in many other forms, and in particular features of any one of the various described examples may be provided in anycombination in any of the other described examples. Various modifications and alterations to this invention will become apparent to those skilled in the art without departing from the scope and spirit of this invention. It should be understood that this invention is not intended to be unduly limited by the illustrative embodiments and examples set forth herein and that such examples and embodiments are presented by way of example only with the scope of the invention intended to be limited only by the claims set forth herein as follows.EMBODIMENTS OF THE INVENTION[000231] Other embodiments of the invention as described herein are defined in the following paragraphs:[000232] A pharmaceutical composition for nasal administration comprising:a) a lipopeptide adjuvant Cys-Dipalmitoyl-Ser-Lys-Lys-Lys-Lys-PEG2-NH2 (otherwise referred to as dipalmitoyl-S-glyceryl-cysteine or Pam2Cys);b) an antigen; andc) mannitol,wherein the composition is formulated as a dry power with more than about 90% of the particles being larger than about 10 pm.[000233] The pharmaceutical composition as described herein, wherein the lipopeptide adjuvant Cys-Dipalmitoyl-Ser-Lys-Lys-Lys-Lys-PEG2-NH2 (dipalmitoyl-S-glyceryl-cysteine) is Pam2Cys.[000234] The pharmaceutical composition as described herein, wherein the antigen comprises a Spike (S) receptor binding domain, protein or an immunogenic fragment or immunogenic variant thereof.[000235] The pharmaceutical composition as described herein, wherein the antigen is derived from the SARS-CoV-2.[000236] The pharmaceutical composition as described herein, wherein the SARS-CoV-2 spike is a delta-variant spike protein.[000237] The pharmaceutical composition as described herein, wherein the composition is frozen at 80 °C for about 2 hours to facilitate freeze-drying and stabilisation of the delta-variant spike protein.[000238] The pharmaceutical composition as described herein, wherein the composition is freeze-dried to produce said dry powder suitable for nasal administration.[000239] The pharmaceutical composition, wherein the dry powder comprises a water content of less than about 1 % w / w.[000240] The pharmaceutical composition as described herein, wherein the dry powder is stored at about 4°C to stabilise the composition prior to nasal administration.[000241] A method of treating and / or preventing a respiratory infection in a subject thereof, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition comprising:a) a lipopeptide adjuvant Cys-Dipalmitoyl-Ser-Lys-Lys-Lys-Lys-PEG2-NH2 (otherwise referred to as dipalmitoyl-S-glyceryl-cysteine or Pam2Cys);b) an antigen;c) and mannitol,wherein the composition is formulated as a dry power with more than about 90% of the particles being larger than about 10 pm.[000242] The method as described herein, wherein the lipopeptide adjuvant dipalmitoyl-S-glyceryl-cysteine is Pam2Cys.[000243] The method as described herein, wherein the antigen comprises a Spike (S) receptor binding domain, protein or an immunogenic fragment or immunogenic variant thereof.[000244] The method as described herein, wherein the antigen is derived from the SARS-CoV-2.[000245] The method as described herein, wherein the SARS-CoV-2 spike is a delta-variant spike protein.[000246] The method as described herein, wherein the respiratory infection is selected from the group consisting of: coronavirus, rhinovirus, influenza, respiratory, syncytial virus, adenovirus, parainfluenza and metapneumovirus, and Epstein-Barr virus and bacterial infections such as Mycobacterium tuberculosis.[000247] The method of treating and / or preventing a respiratory infection in a subject thereof, as described herein, wherein the composition is freeze-dried to produce said dry powder suitable for nasal administration.[000248] The method as described herein, wherein the dry powder comprises a water content of less than about 1 % w / w.[000249] The method, wherein the dry powder is stored at about 4°C to stabilise the composition prior to nasal administration.[000250] The method as described herein, wherein the respiratory infection is selected from the group consisting of: coronavirus, rhinovirus, influenza, respiratory, syncytial virus, adenovirus, parainfluenza and metapneumovirus, and Epstein-Barr virus.[000251] The method as described herein, wherein the respiratory infection is coronavirus.[000252] The method as described herein, wherein the coronavirus infection is SARS-CoV-2.[000253] The method as described herein, wherein the SARS-CoV-2 antigen is selected from alpha, beta, gamma, kappa or delta strains or variants.[000254] The method as described herein, wherein SARS-CoV-2 is the delta strain.[000255] The method as described herein, wherein the composition upon administration, induces spike-specific neutralising antibodies in the blood and T cells in the nasal passages and lungs of the subject.[000256] The method as described herein, wherein the spike-specific and neutralising antibodies are IgG and IgA in the blood, nasal passages and in the BALF and the spike-specific T cells is CD4+ T cells.[000257] Use of a composition in the manufacture of a medicament for treating and / or preventing a respiratory infection in a subject thereof comprising:a) a lipopeptide adjuvant Cys-Dipalmitoyl-Ser-Lys-Lys-Lys-Lys-PEG2-NH2 (otherwise referred to as dipalmitoyl-S-glyceryl-cysteine or Pam2Cys);b) an antigen; andc) mannitol,wherein the composition is formulated as a dry power with more than about 90% of the particles being larger than about 10 pm.[000258] The use as described herein, wherein the lipopeptide adjuvant dipalmitoyl-S-glyceryl-cysteine is Pam2Cys.[000259] The use as described herein, wherein the antigen comprises a Spike (S) receptor binding domain, protein or an immunogenic fragment or immunogenic variant thereof.[000260] The use as described herein, wherein the antigen is derived from the SARS-CoV-2.[000261] The use as described herein, wherein the SARS-CoV-2 spike is a delta-variant spike protein.[000262] The use as described herein, wherein the composition is freeze-dried to produce said dry powder suitable for nasal administration.[000263] The use as described herein, wherein the dry powder comprises a water content of less than about 1 % w / w.[000264] The use as described herein, wherein the dry powder is stored at about 4 °C to stabilise the composition prior to nasal administration.[000265] The use as described herein, wherein the respiratory infection is selected from the group consisting of: coronavirus, rhinovirus, influenza, respiratory, syncytial virus, adenovirus, parainfluenza and metapneumovirus, and Epstein-Barr virus, and bacterial infections such as Mycobacterium tuberculosis.[000266] The use as described herein, wherein the respiratory infection is coronavirus.[000267] The use as described herein, wherein the coronavirus infection is SARS-CoV-2.[000268] The use as described herein, wherein the SARS-CoV-2 antigen is selected from alpha, beta, gamma, kappa or delta strains or other variants.[000269] The use as described herein, wherein SARS-CoV-2 is the delta strain.[000270] The use as described herein, wherein the composition upon administration, induces spike-specific neutralising antibodies and T cells in the blood, nasal passages and lungs of the subject.[000271] The use as described herein, wherein the spike-specific and neutralising antibodies are IgG and IgA in the blood, nasal passages and in the BALF and the spike-specific T cells is CD4+ T cells.[000272] A pharmaceutical composition for use in treating and / or preventing respiratory infection in a subject thereof comprising:d) a lipopeptide adjuvant Cys-Dipalmitoyl-Ser-Lys-Lys-Lys-Lys-PEG2-NH2 (otherwise referred to as dipalmitoyl-S-glyceryl-cysteine or Pam2Cys);e) an antigen;f) and mannitol,wherein the composition is formulated as a dry power with more than about 90% of the particles being larger than about 10 pm.[000273] The pharmaceutical composition for use as described herein, wherein the lipopeptide adjuvant Cys-Dipalmitoyl-Ser-Lys-Lys-Lys-Lys-PEG2-NH2 is Pam2Cys.[000274] The pharmaceutical composition for use as described herein, wherein the antigen comprises a Spike (S) receptor binding domain, protein or an immunogenic fragment or immunogenic variant thereof.[000275] The pharmaceutical composition for use as described herein, wherein the antigen is derived from the SARS-CoV-2.[000276] The pharmaceutical composition for use as described herein, wherein the SARS-CoV-2 spike is a delta-variant spike protein.[000277] The pharmaceutical composition for use as described herein, wherein the composition is freeze-dried to produce said dry powder suitable for nasal administration.[000278] The pharmaceutical composition for use as described herein, wherein the dry powder comprises a water content of less than about 1% w / w.[000279] The pharmaceutical composition for use as described herein, wherein the dry powder is stored at about 4 °C to stabilise the composition prior to nasal administration.[000280] The pharmaceutical composition for use as described herein, wherein the respiratory infection is selected from the group consisting of: coronavirus, rhinovirus, influenza, respiratory, syncytial virus, adenovirus, parainfluenza and metapneumovirus, and Epstein-Barr virus, and bacterial infections such as Mycobacterium tuberculosis.[000281] The pharmaceutical composition for use as described herein, wherein the respiratory infection is coronavirus.[000282] The pharmaceutical composition for use as described herein, wherein the coronavirus infection is SARS-CoV-2.[000283] The pharmaceutical composition for use as described herein, wherein the SARS-CoV-2 antigen is selected from alpha, beta, gamma, kappa or delta strains or other variants.[000284] The pharmaceutical composition for use as described herein, wherein SARS-CoV-2 is the delta strain.[000285] The pharmaceutical composition for use, wherein the composition upon administration, induces spike-specific neutralising antibodies and T cells in the blood, nasal passages and lungs of the subject.[000286] The pharmaceutical composition for use as described herein, wherein the spikespecific and neutralising antibodies are IgG and IgA in the blood, nasal passages and in the BALF and the spike-specific T cells is CD4+ T cells.[000287] The pharmaceutical composition, method, use, and for use as described herein, wherein the composition comprises an excipient selected from a non-reducing sugar, an amnio acid, an antioxidant, and any combinations thereof. For example, the non-reducing sugar may be trehalose, sucrose, or raffinose, the animo acid may be glycine, arginine, or histidine, and the antioxidant may be methionine, glutathione, sodium ascorbate, or a-tocopherol acetate. The pharmaceutical composition may comprise an adjuvant, an antigen, mannitol, and an additional excipient selected from a non-reducing sugar, an amnio acid, an antioxidant, and any combinations thereof.[000288] The pharmaceutical composition, method, use, and for use as described herein, wherein the antigen is derived from the SARS-CoV-2, Influenza A (IAV), Respiratory Syncytial Virus (RSV), or Epstein-Barr Virus (EBV).[000289] The pharmaceutical composition, method, use, and for use as described herein, wherein the antigen comprises a protein or an immunogenic fragment or immunogenic variant thereof derived from a virus. The virus may be a coronavirus, influenza, RSA, or EBV.[000290] The pharmaceutical composition, method, use, and for use as described herein, wherein the antigen comprises Hemagglutinin (HA) or Neuraminidase (NA) of IAV, pre-Fusion (F) protein or Glycoprotein (G) of RSV, or gB, gp350, gHgL, or gHgLgp42 of EBV.

Claims

CLAIMS1. A pharmaceutical composition for nasal administration comprising:a) a lipopeptide adjuvant Cys-Dipalmitoyl-Ser-Lys-Lys-Lys-Lys-PEG2-NH2 (otherwise referred to as dipalmitoyl-S-glyceryl-cysteine or Pam2Cys);b) an antigen; andc) mannitol,wherein the composition is formulated as a dry power with more than about 90% of the particles being larger than about 10 pm.

2. The pharmaceutical composition of claim 1, wherein the lipopeptide adjuvant Cys- Dipalmitoyl-Ser-Lys-Lys-Lys-Lys-PEG2-NH2 is Pam2Cys.

3. The pharmaceutical composition of claim 1 or claim 2, wherein the antigen comprises a Spike (S) receptor binding domain, protein or an immunogenic fragment or immunogenic variant thereof.

4. The pharmaceutical composition of claim 3, wherein the antigen is derived from the SARS-CoV-2.

5. The pharmaceutical composition of claim 4, wherein the SARS-CoV-2 spike is a deltavariant spike protein.

6. The pharmaceutical composition of any one of claims 1 to 5, wherein the composition comprises:a) about 0.3% w / v of Pam2Cys;b) about 0.3% w / v of a delta-variant spike protein; andc) about 99.3% w / v of mannitol.

7. The pharmaceutical composition of claim 6, wherein the composition is frozen at about - 80°C for about 2 hours to facilitate freeze-drying and stabilisation of the delta-variant spike protein.

8. The pharmaceutical composition of any one of claims 1 to 7, wherein the composition comprises an excipient selected from a non-reducing sugar, an amino acid, an antioxidant, and any combinations thereof.

9. The pharmaceutical composition of claim 8, wherein the non-reducing sugar is trehalose, sucrose, or raffinose, the amino acid is glycine, arginine, or histidine, and the antioxidant is methionine, glutathione, sodium ascorbate, or a-tocopherol acetate.

10. The pharmaceutical composition of any one of claims 1 to 9, wherein the composition is freeze-dried to produce said dry powder suitable for nasal administration.

11. The pharmaceutical composition of claim 10, wherein the dry powder comprises a water content of less than about 1 % w / w.

12. The pharmaceutical composition of any one of claims 1 to 11, wherein the dry powder is stored at about 4°C to stabilise the composition prior to nasal administration.

13. A method of treating and / or preventing a respiratory infection in a subject in need thereof, the method comprising administering to the subject an effective amount of the pharmaceutical composition of any one of claims 1 to 12.

14. Use of the pharmaceutical composition of any one of claims 1 to 12 in the manufacture of a medicament for treating and / or preventing a respiratory infection in a subject.

15. The method of claim 13, or the use of claim 14, wherein the respiratory infection is selected from the group consisting of: coronavirus, rhinovirus, influenza, respiratory, syncytial virus, adenovirus, parainfluenza and metapneumovirus, and Epstein-Barr virus and bacterial infections such as Mycobacterium tuberculosis.

16. The method or the use of claim 15, wherein the respiratory infection is coronavirus.

17. The method or the use of claim 16, wherein the coronavirus infection is SARS-CoV-2.

18. The method or the use of claim 17, wherein the SARS-CoV-2 antigen is selected from alpha, beta, gamma, kappa or delta strains or other variants.

19. The method or the use of claim 18, wherein SARS-CoV-2 is the delta strain.

20. The method or the use of claim 19, or the pharmaceutical composition of any one of claims 1 to 12, wherein the composition or medicament upon administration, induces spike-specific neutralising antibodies and T cells in the blood, nasal passages and lungs of the subject.

21. The method or the use of claim 20, or the pharmaceutical composition of any one of claims 1 to 12, wherein the spike-specific neutralising antibodies are IgG and IgA in the blood, nasal passages, and bronchoalveolar lavage fluid (BALF), and the spike-specific T cells is CD4+ T cells.

22. A pharmaceutical composition of any one of claims 1 to 12 for use in treating and / or preventing a respiratory infection in a subject.

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