Inactivated whole virion vaccine against influenza and methods of use thereof

Abstract

Provided herein are methods for inactivating an influenza particle, the methods comprising contacting the influenza particle with UV light in the presence of riboflavin such that the integrity of the antigenic proteins of the influenza particle are preserved. Vaccine compositions comprising inactivated influenza particles, and methods of use thereof, are also provided

Description

[0001] 2023-048 INACTIVATED WHOLE VIRION VACCINE AGAINST INFLUENZA AND METHODS OF USE THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS This International PCT Application claims the benefit of and priority to U.S. Provisional Application No.63 / 533,211 filed August 17, 2023, the specification, claims and drawings of which are incorporated herein by reference in their entirety. SEQUENCE LISTING The instant application contains contents of the electronic sequence listing (90013.00121- Sequence-Listing.xml; Size: 3000 bytes; and Date of Creation: August 13, 2024) is herein incorporated by reference in its entirety. TECHNICAL FIELD The inventive technology is directed to the design, production, and use of vaccines, and in particular the design, production, and use of novel whole virion vaccine directed against influenza. BACKGROUND Influenza continues to have a significant impact on human health globally, with approximately 20,000-50,000 deaths reported each year and millions more reporting clinical symptoms which can often be debilitating. Vaccines are an effective tool in combating the disease burden globally. However, traditional vaccines are only 40-60% effective as new influenza strains emerge every year. Inactivated vaccines using beta-propiolactone and formalin are commercially available to protect against influenza in the human population. However, these vaccines often require i) harsh chemical or physical processes to prevent viral replication, and ii) complex, expensive, and time-consuming production steps to remove toxic byproducts to below a rigorous threshold. Perhaps more importantly, these methods damage essential components of the virus that serve as antigenic targets, leading to reduced vaccine efficacy.. Non-pandemic influenza vaccine sales are expected to grow to $6.5B by 2028 and remain dominated by egg-grown products, which require significant lead times and are difficult to scale. Thus, there is a need in the art for improved compositions and methods for producing inactivated viral vaccines, which inactivate a virus particle’s ability to replicate while preserving the potency and integrity of the antigenic proteins thereon. In particular, there is a need in the art for compositions and methods for producing an inactivated viral vaccine against influenza. 2023-048 To address this long-felt need, the present inventors have developed a novel method to inactivate viruses and create inactivated vaccines using a photochemical reaction. By using a combination of UV light and riboflavin, viruses are inactivated at the nucleic acid level to prevent viral replication while preserving key immunogenic antigens needed to develop a protective immunity against the disease. This novel vaccine platform, generally referred to as SolaVAX™ below, allows for the rapid manufacturing of inactivated viruses including novel influenza strains / variants that impact human health every season. Specifically, the SolaVAX™ technology uses a combination of riboflavin (vitamin B2) and UV light to rapidly inactivate whole pathogens, while maintaining integrity of the antigen profile. SolaVAX™ does not rely on toxic inactivating chemicals that can compromise antigen conformation (‘antigen masking’) and add to manufacturing complexity, especially at scale. As a result, the SolaVAX™ method enhances both the speed and lower the cost of producing influenza vaccines as described below. BRIEF SUMMARY OF THE INVENTION Provided herein are compositions and methods for producing inactivated influenza viral vaccines, including vaccines against influenza. The compositions and methods employ the use of a photochemical (e.g., riboflavin) in combination with UV light to carry out specific nucleic acid alterations through electron transfer chemistry-based processes. When combined with UV light, these photochemicals modify nucleic acid structure, primarily through modification of guanine bases. The specificity of the riboflavin photochemistry used in this process substantially avoids the alkylation, crosslinking and covalent modifications that are associated with other chemical and photochemical mechanisms of traditional viral inactivation. Unlike the standard chemical agents such as beta-propiolactone and ethyleneimine derivatives that are routinely used for inactivated vaccine production, the photochemicals used in the disclosed approaches (e.g., riboflavin) have well-established safety toxicology profiles, are non-mutagenic and non-carcinogenic and pose little to no toxicity or disposal risk to facility personnel or the environment. The present invention further relates to influenza viral vaccines and methods for preparing the same. More specifically, in one preferred embodiment the present invention relates to methods for inactivation of influenza viral particles, including influenza viral particles, using a photosensitizer such as riboflavin in combination with UV light. Also provided herein is a method for producing a viral vaccine, the method comprising (i) providing a plurality of influenza particles, and (ii) inactivating the particles by contacting them with UV light in the presence of 2023-048 riboflavin. In some embodiments, the method comprises purifying the inactivated influenza particles. Also provided herein is a method for inactivating an influenza viral particle, the method comprising contacting the influenza viral particle with a dose of UV light in the presence of riboflavin; wherein the dose of UV light is about 100 Joules to about 1000 Joules; wherein the method comprises selectively oxidizing about 1 to about 30 guanine bases in a nucleic acid of the viral particle; and wherein the method does not comprise substantially altering the structure of antigens on the viral particle. In some embodiments, the method comprises selectively oxidizing about 9 guanine bases in the nucleic acid of the viral particle. In some embodiments, the method comprises selectively oxidizing about 20 guanine bases in the nucleic acid of the viral particle. In some embodiments, the nucleic acid of the viral particle is an RNA, and more specifically a single -stranded RNA (ssRNA). In some embodiments, the invention includes a vaccine composition comprising an inactivated influenza particle and a pharmaceutically acceptable carrier or excipient Also provided herein is a method for treating or preventing a viral infection in a subject in need thereof, the method comprising administering to the subject an effective amount of the influenza vaccine composition as described herein. In some embodiments, the subject is a mammal. In some embodiments, the subject is a human. In some embodiments, the vaccine is administered intramuscularly. In some embodiments, the vaccine is administered subcutaneously. Additional aspects of the invention are described in the specification and drawings provided herein. BRIEF DESCRIPTION OF DRAWINGS FIG.1A-B: Retention of HA Protein. FIG.2: Mouse Antibody Generation Post-Vaccination with SolaVAX-INF. FIG.3: Neutralizing antibody response in mice 56 days after vaccination with inactivated SolaVAX vaccine. FIG.4: Neutralizing antibody response after vaccination. FIG. 5: General strategy of SolaVAX method of inactivation which employs riboflavin photochemistry to carry out specific nucleic acid modifications, creating whole virion vaccines with damaged nucleic acid but intact antigens. 2023-048 FIG.6: Inactivation via SolaVAX method of seasonal influenza strains used in the 2023- 2024 influenza vaccine formulation recommended by the WHO, including 2 Influenza A strains (A / Wisconsin / 67 / 2022 H1N1 (A), A / Darwin / 6 / 2021 H3N2 (B)) and 2 Influenza B strains (B / Austria / 1359417 / 2021 (C), B / Phuket / 3073 / 2013 (D)). Each strain was propagated in MDCK cells then treated by SolaVAX method at incremental energy doses of 0.5J / ml until complete inactivation was achieved. Confirmation of inactivation was confirmed by plaque assay to demonstrate no infectious particles were present after treatment. Viral titers detected by plaque assay before and after SolaVAX treatment. Limit of detection for the plaque assay is 1 log10 pfu / ml (dotted line). Each virus strain was tested in duplicates. Applicant’s identified that 2J / ml of energy is sufficient to fully inactivate influenza A and B virus strains by the SolaVAX method. FIG. 7: (A) Influenza A (H3N2) hemagglutinin antigenicity before and after SolaVAX treatment; and (B) Influenza B) hemagglutinin antigenicity before and after SolaVAX treatment. DETAILED DESCRIPTION OF INVENTION Described herein are compositions and methods for producing inactivated viral vaccines, including vaccines for influenza. The compositions and methods disclosed herein take advantage of a unique property of the photosensitizer riboflavin and UV light to selectively inactivate virus particles by directed damage to nucleic acids while preserving the integrity of the proteins and other viral antigens. The nature of the photosensitizer (riboflavin) provides for low toxicity and thus easy handling, distribution and processing under even austere conditions. In some embodiments, the disclosed methods can produce up to 3 million doses of vaccine in less than 5 minutes, making rapid and affordable production of an inactivated vaccine both practical and cost- effective. Throughput calculations indicate that within 1 month, a sufficient amount of vaccine product can be manufactured for every person on the planet at a reasonable cost, using disclosed compositions and methods. A significant advantage of the disclosed methods is that the photochemical, riboflavin, is inexpensive, has been demonstrated to be non-toxic and does not pose safety or environmental concerns. This stands in sharp contrast to many of the agents currently in use for preparation of inactivated vaccines such as glutaraldehyde, formaldehyde, Aldrithiol-2, ethyleneimine derivatives and irradiation technologies. The use of these inactivating chemistries requires facilities for production in very specialized operations with training for personnel and waste 2023-048 disposal processes that are cumbersome and difficult to produce in mobile facilities and operation under austere environmental conditions. Another advantage is that the specific chemistry induced by riboflavin / UV inactivation allows more influenza virus vaccine candidates to be prepared via this route, since the selectivity in chemistry is more likely to preserve labile and sensitive antigen profiles that are destroyed by the methods commonly used in the art. Such production methods, including VRP (virus replication particle) and VLP (virus-like particle) technology platforms, often require multiple steps of disassembly and re-assembly under controlled conditions. In the processes described herein, the virus or target agent is inactivated in situ in its native form. The processes described herein inactivate nucleic acid replication without requiring additional processing steps to remove replication potential in the target agent. This approach is therefore useful to enhance the safety profile for viral vaccine candidates that contain nucleic acids. Such a reduction in processing steps and the requirements for extended protein stability throughout processing easily extend the application of this approach to agents generally considered up to this point to not be amenable to preparation of vaccine candidates. Thus, the disclosed approach allows for vaccine production in an austere environment with minimal facility and personnel training needs. The vaccine compositions described herein can be used, for example, for influenza vaccination of at-risk subjects, including healthcare workers and those working with potentially infected animals. As used herein, the term “influenza” refers to a disease caused by the influenza virus. As used herein, “influenza virus” (“IF” or “IFV”), is the causative agent of influenza. As further used herein, influenza virus includes any strain of influenza virus that is capable of causing disease in animals or humans, or that is of interest as a candidate for experimental analysis. refers to a reference species of the Orthomyxoviridae family. The influenza virus according to the present invention is as described above. The influenza virus according to the present invention is preferably an influenza A or B virus. The influenza A or B or C virus can be any strain of virus. As used herein, “influenza A virus” includes all genetic variants of the virus including those that can cause the disease influenza A or Flu A. Influenza A is virus a negative-sense, single- stranded, segmented RNA virus. The several subtypes are labeled according to an H number (for the type of hemagglutinin and a N number (for the type of neuraminidase). There are 18 different 2023-048 known H antigens (H1 to H18) and 11 different known N antigens (N1 to N11). For example, H17N10 was isolated in 2012 and H18N11 was discovered in 2013. Specifically, in a preferred embodiment, the influenza A virus can be is selected from the group consisting of H1N1, H2N2, H3N1, H3N2, H3N8, H5N1, H7N1, H7N7, H1N2, H9N2, H7N2, H7N3, and H10N7 viruses. Influenza virus proteins: “influenza virus proteins”, as used herein, denote the PB1 , PB2, PA, HA, NP, NA, M1 , M2, NS1 and NS2 / NEP proteins for type A influenza, PB1 , PB2, PA, HA, NP, NA, NB, M1 , BM2, NS1 and NS2 / NEP proteins for type B influenza, or PB1 , PB2, PA, HEF, NP, M1 , M1 \ CM2, NS1 and NS2 / NEP for type C influenza. As used herein, “influenza B virus” includes all genetic variants of the virus including those that can cause the disease influenza B or Flu B. Influenza B virus is the only species in the genus Betainfluenzavirus in the virus family Orthomyxoiridae, a family of negative-sense RNA viruses. There are two known circulating lineages of Influenza B virus based on the antigenic properties of the surface glycoprotein hemagglutinin. The lineages are termed B / Yamagata-like and B / Victoria-like viruses. Influenza B virus, like influenza A, has a linear, negative-sense single-stranded RNA segmented genome. As used herein, the term “influenza structural protein” refers to any protein associated with the influenza nucleocapsid, matrix and envelope, including the surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), and the matrix (M1) protein and proton ion-channel protein (M2), and functional or antigenic fragments thereof. By contrast, non-structural proteins of the influenza virus include influenza virus proteins necessary to form the ribonucleoprotein complex. By “influenza virus proteins necessary to form the ribonucleoprotein complex” means proteins PA, PB1, PB2 and NP for type A, B or C influenza virus. Non-structural proteins also include NS1 and NS2. Exemplary influenza Strains and Isolates of the present invention can include but are not limited to the strains and isolates provided in Table 1 below. In some embodiments, the influenza is any strain of influenza now known or later discovered. In some embodiments, the influenza is A / California / 07 / 2009(H1N1)) Gene Bank Accession No. GCA_000865085.1, or a sequence with about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% sequence identity relative thereto. In some embodiments, the influenza has a genome with about 1 to about 100, about 100 to about 250, or about 250 or about 500 nucleic acid substitutions relative to the genome of Gene Bank Accession No. GCA_000865085. In some embodiments, the 2023-048 influenza has a genome sequence with at least about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% sequence identity relative isolate A / California / 07 / 2009(H1N1)) Gene Bank Accession No. GCA_000865085.1. In some embodiments, the influenza is an influenza having an HA protein according to SEQ ID NO. 1, or a sequence with about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% sequence identity relative thereto. In some embodiments, the HA protein has a sequence with about 1 to about 100, about 100 to about 250, or about 250 or about 500 or more nucleic acid substitutions relative to the nucleotide sequence that encodes the HA protein according to SEQ ID NO.1. Inactivated Viral Vaccine Compositions Provided herein are inactivated viral vaccine compositions. The compositions comprise, consist essentially of, or consist of inactivated viral influenza particles or fragments or derivatives thereof. The influenza viral particles are inactivated by modifying their RNA, rendering them incapable of causing disease. In some embodiments, the modification of the viral RNA renders the influenza virus incapable of replicating but does not kill the virus. Because the inactivation process does not substantially alter the structure of antigens (e.g., protein and / or lipid antigens) on the influenza viral particles, when administered to a subject in need thereof, the vaccines comprising the inactivated particles present antigenic targets, such as the HA proteins, to the subject’s immune system that are substantially identical to those present on a pathogenic, replication-competent influenza virus. Administration of the vaccine compositions to a subject in need thereof stimulates an immune response to the virus, therefore preventing or treating a viral infection in the subject. In some embodiments, the inactivated influenza viral vaccine comprises, consists essentially of, or consists of influenza viral particles inactivated using a photochemical process to inactivate the disease-causing ability of the virus while preserving protein structure and phenotype. In some embodiments, the RNA of the inactivated influenza viruses comprises modified bases. For example, in some embodiments the RNA of the inactivated influenza viruses may comprise modified guanine bases, such as oxidized guanine bases. In some embodiments, an inactivated influenza viral particle comprises about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, about 20, about 21, about 22, about 2023-048 23, about 24, about 25, about 26, about 27, about 28, about 29, about 30 or more modified guanine bases, such as oxidized guanine bases, in its genome. In some embodiments, an influenza particle comprises about 9 modified guanine bases in its genome. In some embodiments, an influenza particle comprises about 16 modified guanine bases in its genome. In some embodiments, an influenza particle comprises about 17 modified guanine bases in its genome. In some embodiments, an influenza particle comprises about 18 modified guanine bases in its genome. In some embodiments, an influenza particle comprises about 19 modified guanine bases in its genome. In some embodiments, an influenza particle comprises about 20 modified guanine bases in its genome. In some embodiments, an influenza particle comprises about 21 modified guanine bases in its genome. In some embodiments, an influenza particle comprises about 22 modified guanine bases in its genome. In some embodiments, an influenza particle comprises about 23 modified guanine bases in its genome. In some embodiments, an influenza particle comprises about 24 modified guanine bases in its genome. In some embodiments, the inactivated influenza viral vaccine composition further comprises one or more agonists or antagonists. In some embodiments, the agonist is a Toll-Like Receptor (TLR) agonist. In some embodiments, the TLR agonist is an agonist of one or more of TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, or TLR12. In some embodiments, the agonist is a TLR3 and / or a TLR9 agonist. In some embodiments, the antagonist is a C-C chemokine receptor type 2 (CCR2) antagonist. In some embodiments, the antagonist is an angiotensin receptor blocker (ARB), such as losartan, telmisartan, irbesartan, azilsartan, candesartan, eprosartan, olmesartan, or valsartan. In some embodiments, the ARB is administered at a dose of between about 5 and about 100 mg / kg, for example about 5, about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, or about 100 mg / kg. In some embodiments, the inactivated virus vaccine comprises at least one of (i.e., one of, two of, or all three of) a TLR agonist, a CCR2 antagonist and an ARB. In some embodiments, the agonist or antagonist (e.g., a TLR3 and / or a TLR9 agonist) is contained within or coupled to a liposome. Liposomes are spherical, self-enclosed vesicles composed of amphipathic lipids. Liposomes may be unilamellar, having one lipid bilayer membrane, or multilamellar, having two or more concentrically arranged bilayers. Suitable 2023-048 liposomes may have a selected mean particle size diameter of about 200-500 nm. Various methods of preparing liposomes and encapsulation of therapeutic agents therein are well documented (see, for example, U.S. Pat. Nos. 3,932,657, 4,311,712, and 5,013,556, all of which are incorporated herein by reference). Known methods include the reverse phase evaporation method as described in U.S. Pat. No.4,235,871, which is incorporated herein by reference. Lipids for use in forming the liposomes described herein include vesicle-forming lipids having two hydrocarbon chains, typically acyl chains, and a polar head group. Included in this class are the phospholipids, such as phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidic acid (PA), phosphatidylinositol (PI), and sphingomyelin (SM), where the two hydrocarbon chains are typically between about 14-22 carbon atoms in length and have varying degrees of unsaturation. The selection of lipids and proportions can be varied to achieve a desired degree of fluidity or rigidity, to control stability, and / or to control the rate of release of an entrapped agent. Where more than one type of lipid is used, a suitable amount of a relatively unsaturated lipid (such as PC), may be used in order to form stable liposomes. In one embodiment, at least 45- 50 mol % of the lipids used to form the liposome are PC. The liposomes may also include lipids derivatized with a hydrophilic polymer such as polyethylene glycol (PEG). Suitable hydrophilic polymers include polyvinylpyrrolidone, polyvinylmethylether, polymethyloxazoline, polyethyloxazoline, polyhydroxypropyloxazoline, polyhydroxypropylmethacrylamide, polymethacrylamide, polydimethylacrylamide, polyhydroxypropylmethacrylate, polyhydroxyethylacrylate, hydroxymethylcellulose, hydroxyethylcellulose, polyethyleneglycol, polyaspartamide, and hydrophilic peptide sequences. Methods of preparing lipids derivatized with hydrophilic polymers are known (see e.g., U.S. Pat. No, 5,395,619, which is incorporated herein by reference). In some embodiments, the inactivated viral vaccine comprises cationic liposome-DNA complexes (CLDC). In some embodiments, the inactivated influenza viral vaccine further comprises a photosensitizer such as riboflavin (vitamin B2). In some embodiments, the inactivated influenza viral vaccine is substantially free of photosensitizer. In some embodiments, the inactivated influenza viral vaccine composition further comprises a carrier. In some embodiments, the cells and / or the photosensitizer are suspended in the carrier. In some embodiments, the carrier comprises normal saline (e.g., 0.9% sodium 2023-048 chloride), dextrose saline (e.g., dextrose 5% in 0.9% sodium chloride), phosphate buffered saline (e.g., 137 mmol / L NaCl, 2.7 mmol / L KCl, 10 mmol / L Na2HPO4, 2 mmol / L KH2PO4). In some embodiments, the inactivated influenza viral vaccine composition further comprises one or more additional pharmaceutically acceptable ingredients well known to those skilled in the art, including, but not limited to, pharmaceutically acceptable carriers, diluents, excipients, fillers, buffers, preservatives, antioxidants, lubricants, stabilizers, solubilizers, surfactants (e.g., wetting agents), masking agents, coloring agents, flavoring agents, and sweetening agents. Suitable carriers, diluents, excipients, and the like can be found in standard pharmaceutical texts. See, for example, Handbook of Pharmaceutical Additives, 2nd Edition (eds. M. Ash and I. Ash), 2001 (Synapse Information Resources, Inc., Endicott, New York, USA), Remington's Pharmaceutical Sciences, 20th edition, pub. Lippincott, Williams & Wilkins, 2000; and Handbook of Pharmaceutical Excipients, 2nd edition, 1994. In some embodiments, a vaccine composition comprises an inactivated influenza viral particle; wherein the composition comprises about 15 to about 50 picograms of viral protein (e.g., about 35 picograms of viral protein). In some embodiments, a vaccine composition comprises an inactivated influenza viral particle; wherein the genome of the influenza viral particle comprises about 1 to about 30 oxidized guanine residues (e.g., about 9 or about 20 oxidized guanine residues); wherein the structure of influenza antigens on the viral particle is not substantially altered compared to influenza viral particle that has not been inactivated. In some embodiments, a vaccine composition comprises inactivated influenza viral particles from multiple influenza strains. For example, in some embodiments, a vaccine composition comprises an inactivated influenza particle from a first strain, and a second inactivated influenza particle from a separate strain. In some embodiments, a vaccine composition comprises inactivated influenza particles from at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten different influenza strains. Methods of Producing Inactivated Viral Vaccines The inactivated influenza viral vaccines described herein are produced using an innocuous chemical agent in a selective process that prevents cellular replication processes while preserving antigenic protein structure. More specifically, the inactivated influenza viral vaccines are produced by the combined application of a photosensitizer and light for rendering influenza viral particles 2023-048 unable to cause disease. The process for producing the inactivated influenza viral vaccines of the disclosure is described in detail below. Initially, influenza viral particles are provided. The influenza viral particles may be recombinant viral particles. Next, the influenza viral particles are inactivated using photochemical technology. This is achieved using photosensitizers that can act as electron transfer agents. The application of photosensitizer agents that can be placed into an excited state in proximity to a guanine base in RNA constructs allows for selective modification (e.g., oxidation, cross-linking, fragmentation, deamination) of these bases. Because electron chemistry can only occur over short distances, the photosensitizer agent must be bound or associated with (i.e., intercalated with) the nucleic acid in order to conduct the desired chemistry. In some embodiments, the photosensitizer is a flavin, for example riboflavin (Vitamin B2), flavin mononucleotide, or flavin adenine dinucleotide. In some embodiments, the photosensitizer is a tertiary aliphatic amine (e.g., 1,4-diazabicyclo(2,2,2)octane), a piperazine, (e.g., N-2- hydroxyethylpiperazine-N'-2-ethanesulfonic acid and 1,4-dimethylpiperazine), an amino acid (e.g., tyrosine, tryptophan, histidine, methionine), an enzyme (e.g., superoxide dismutase) or EDTA (ethylenediaminetetraacetic acid). In some embodiments, the photosensitizer is riboflavin. In some embodiments, the influenza viral particles are added to a solution containing the photosensitizer (e.g., riboflavin), or the photosensitizer is added to a solution containing the viral particles. In some embodiments, the concentration of photosensitizer used during inactivation is about 10 µM to about 100 µM, such as about 10 µM, about 15 µM, about 20 µM, about 25 µM, about 30 µM, about 35 µM, about 40 µM, about 45 µM, about 50 µM, about 55 µM, about 60 µM, about 65 µM, about 70 µM, about 75 µM, about 80 µM, about 85 µM, about 90 µM, about 95 µM, about 100 µM, about 200 µM, about 300 µM, about 500 µM, or more. In some embodiments, the solution contains the photosensitizer at a concentration of about 1 µM to about 50 µM, such as about 2 µM, about 3 µM, about 4 µM, about 5 µM, about 6 µM, about 7 µM, about 8 µM, about 9 µM, about 10 µM, about 15 µM, about 20 µM, about 25 µM, about 30 µM, about 35 µM, about 40 µM, about 45 µM, about 50 µM, about 100 µM , about 200 µM, about 300 µM, about 500 µM, or more. In some embodiments, the photosensitizer concentration is less than about 10 µM, such as less than about 9 µM, about 8 µM, about 7 µM, about 6 µM, about 5 µM, about 4 µM, about 3 µM, about 2 µM, or about 1 µM. 2023-048 The solution containing the photosensitizer and the influenza viral particles (optionally, in media) is then subjected to light treatment. In some embodiments, the light treatment comprises treatment with visible light, ultraviolet light, and / or infrared light. The light treatment inactivates a nucleic acid (e.g., RNA) in the influenza viral particles by modifying bases of these nucleic acids. In some embodiments, guanine bases are selectively modified. In some embodiments, guanine bases are selectively oxidized. Oxidized guanine bases cannot be repaired by natural enzymatic and cell repair mechanisms. As such, there is no possibility for reversion of the induced change to a form that would restore the ability of the viral particles to cause disease. In some embodiments, the light treatment comprises treatment with ultraviolet (UV) light. The UV light may be UV-A, UV-B, or UV-C light. The UV light may have a wavelength of 170 to 400 nm, including all ranges and subranges therebetween. For example, in some embodiments, the UV light has a wavelength of 315 to 400 nm, 310 to 320 nm, 280 to 360 nm, 280 to 315 nm, or 180 to 280 nm. The UV light may be provided by UV light sources known in the art, such as the Mirasol®PRT Illumination device (TerumoBCT, Lakewood, Colorado). In some embodiments, the influenza viral particles may be treated with multiple wavelengths of light simultaneously. In some embodiments wherein riboflavin is used as a photosensitizer, UV light having a wavelength of 310 to 320 nm is used. The inventors have determined that this wavelength prevents riboflavin from reacting in free solution, which results in production of undesirable oxygen free radicals. At these wavelengths, riboflavin will selectively react when intercalated with nucleic acid. The dose of the UV light may vary depending on the volume of solution being treated. For example, the dose of the UV light may be between 200-400 Joules (e.g., 300 Joules) for a volume of about 170 to 370 mls of solution. As will be understood by those of skill in the art, the dosage may be adjusted up or down if the volume to be treated is above or below this range. In some embodiments, the dose of UV light may be from about 200 Joules to about 600 Joules, for example about 200, about 225, about 250, about 275, about 300, about 325, about 350, about 375, about 400, about 425, about 450, about 475, about 500, about 525, about 550, about 575, or about 600 Joules. In some embodiments, the volume of viral preparations for illumination may be from about 200 ml to about 600 ml, for example about 200, about 225, about 250, about 275, about 300, about 325, about 350, about 375, about 400, about 425, about 450, about 475, about 500, about 525, about 550, about 575, or about 600 ml. In some embodiments, the dose of 2023-048 UV light may be from about 0.01 Joules / ml to about 1.0 Joules / ml. In some embodiments, the dose of UV light may be from about 0.5 Joules / ml to about 3.0 Joules / ml. For example, the dose of UV light may be about 0.1, about 0.2 about 0.3, about 0.4, about 0.5, about 0.6, about 0.7, about 0.8, about 0.9, about 1.0, about 1.1, about 1.2, about 1.3, about 1.4, about 1.5, about 1.6, about 1.7, about 1.8, about 1.9, about 2.0, about 2.1, about 2.2, about 2.3, about 2.4, about 2.5, about 2.6, about 2.7, about 2.8, about 2.9, or about 3.0 Joules / ml. In some embodiments, the dose of UV light may be about 0.1 Joules / ml. In some embodiments, the dose of UV light may be from about 1 Joules / ml to about 10 Joules / ml, such as about 1.87 Joules / ml, about 3.74 Joules / ml, or about 6.24 Joules / ml. The influenza viral particles may be treated with UV light for about 1 minute to about 60 minutes, for example, about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, or about 60 minutes. In some embodiments, the influenza viral particles are treated with UV light for about 1 minute to about 10 minutes, about 1 minute to about 5 minutes, or about 1 minute to about 3 minutes. In some embodiments, the influenza viral particles are pre-incubated for a predetermined period of time in the solution containing the photosensitizer (e.g., riboflavin) before subjecting the viral particles to the light treatment. In some embodiments, the influenza viral particles are not subjected to any additional purification or modification steps after light treatment. In other embodiments, the influenza viral particles are purified after the light treatment. In some embodiments, the influenza viral particles are concentrated after the light treatment. In some embodiments, the influenza viral particles are combined with one or more additional pharmaceutically acceptable ingredients as described above after light treatment. In some embodiments, the influenza viral particles generated using this method are incapable of replication processes, but substantially maintain and preserve the antigen and epitope profile of the original, native influenza viral particle or antigen. In some embodiments, the inactivation process does not substantially change the phenotype or structure of the viral particles. In some embodiments, because the specificity of the chemistry preserves the antigen profile and viral particle integrity and maintains viral protein and / or lipid structure in its native state, the 2023-048 inactivated influenza viral particles that are produced by this process provide an improved source for antigen presentation. In some embodiments, a method for inactivating an influenza viral particle comprises contacting the influenza viral particle with a dose of UV light in the presence of riboflavin; wherein the dose of UV light is about 100 Joules to about 1000 Joules; wherein the method comprises selectively oxidizing about 1 to about 30 guanine bases (e.g., about 9 or about 30 guanine bases) in a nucleic acid of the influenza viral particle; and wherein the method does not comprise substantially altering the structure of antigens on the viral particle. Methods of Treatment The inactivated influenza viral vaccine compositions described herein can be used as vaccine agents or stimulants for immune system priming and recognition that foster immune responses in subjects. In some embodiments, the inactivated influenza viral vaccine may be administered to a subject to treat or prevent a viral infection, such as an influenza infection. In some embodiments, the subject is assessed for immune function and immune status prior to administration of the vaccine. Such assessments may include, but are not limited to, DTH skin testing, blood tests, lymph node aspirate tests, tumor tissue tests, and / or determination of whether the subject is anergic, B cell responsive, etc. In some embodiments, the subject is not assessed for immune function and immune status prior to administration of the vaccine. In some embodiments, the subject is immunocompetent. In some embodiments, the subject is immunocompromised. Optionally, the vaccine may be used in combination with genetic testing to quantify the degree of immune-responders, or immune non-responders. It will be appreciated by one of skill in the art that appropriate number of influenza viral particles in the vaccine composition can vary. In some embodiments, the vaccine composition comprises about 1 x 103, about 1 x 104, about 1 x 105, about 1 x 106, about 1 x 107, about 1 x 108, about 1 x 109, or about 1 x 1010viral particles. In some embodiments, a vaccine composition comprises about 1 x 105to about 1 x 108influenza viral particles. In some embodiments, about 1x105to about 1x108influenza viral particles are administered to a subject in each administration. For example, about 1x105, about 5x105, about 1x106, about 5x106, about 1x107, about 5x107, or about 1x108influenza viral particles may be administered to a subject per administration. In some embodiments, the administered dose is a split dose, wherein the total number of influenza viral particles for administration is divided into 2, 3, 4, 5, 6, 7, 8, 9, or 10 sub-doses. 2023-048 In some embodiments, about 10 to about 100 micrograms of influenza viral protein are administered to a subject in each administration. In some embodiments, about 1 to about 100 picograms of influenza viral protein are administered to a subject in each administration. In some embodiments, about 15 to about 50 picograms, or about 30 to about 40 picograms of influenza viral protein are administered to a subject in each administration. For example, about 5, about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, or about 100 picograms of influenza viral protein may be administered to a subject in each administration. In some embodiments, about 10 picograms of influenza viral protein are administered to a subject in each administration. In some embodiments, about 11 picograms of influenza viral protein are administered to a subject in each administration. In some embodiments, about 12 picograms of influenza viral protein are administered to a subject in each administration. In some embodiments, about 13 picograms of influenza viral protein are administered to a subject in each administration. In some embodiments, about 14 picograms of influenza viral protein are administered to a subject in each administration. In some embodiments, about 15 picograms of influenza viral protein are administered to a subject in each administration. In some embodiments, about 16 picograms of influenza viral protein are administered to a subject in each administration. In some embodiments, about 17 picograms of influenza viral protein are administered to a subject in each administration. In some embodiments, about 35 picograms of influenza viral protein are administered to a subject in each administration. In some embodiments, the administered dose is a split dose, wherein the total amount of influenza viral protein for administration is divided into 2, 3, 4, 5, 6, 7, 8, 9, or 10 sub-doses. One or more sub-doses may be administered to the subject peripherally at different locations on the subject’s body. Each sub-dose may be administered at approximately the same time, or administration of the sub-doses may be staggered. For example, sub-doses may be administered at intervals of 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, or 3 hours. In some embodiments, the inactivated influenza viral vaccine is administered once, or more than once to the subject. In some embodiments, the vaccine is administered once, twice, three times, four times, five times, six times, seven times, eight times, nine times, or ten times to the subject. 2023-048 The inactivated influenza viral vaccine may be administered to the subject every day, about every 3 days, about every 7 days, about every fourteen days, about once per month, or about once per year. In some embodiments, the influenza vaccine is administered at least once per week, at least every two weeks, or at least once every six months. In some embodiments, the influenza vaccine is administered once, twice, three times, four times, five times, six times, seven times, eight times, nine times, ten times, twelve times, fifteen times, twenty times, or twenty-five times in a year. In some embodiments, a first dose (e.g., a prime dose) of inactivated influenza viral vaccine is administered, followed by a second dose (e.g., a boost dose) to the subject. In some embodiments, the second dose is administered about 1 week, about 2 weeks, about 3 weeks, about 4 weeks, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, or about 1 year after the first dose. In some embodiments, the amount of influenza viral protein in the first dose is greater than the amount of influenza viral protein in the second dose. For example, the amount of viral protein may be about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or about 100% greater than the amount of influenza viral protein in the first dose. In some embodiments, the amount of influenza viral protein in the first dose is less than the amount of influenza viral protein in the second dose. For example, the amount of influenza viral protein may be about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or about 100% less than the amount of influenza viral protein in the first dose. In some embodiments, the amount of influenza viral protein in the first dose is about the same as the amount of influenza viral protein in the second dose. In some embodiments, a first inactivated influenza viral vaccine and a second inactivated influenza viral vaccine are administered to the subject. In some embodiments, the second inactivated influenza viral vaccine is administered after the first vaccine to boost the immune response. In some embodiments, immune response in the subject is monitored between administration of the first vaccine and the second vaccine. In some embodiments, the second vaccine is administered when it is determined that the subject has not exhibited a satisfactory immune response following administration of the first vaccine. The inactivated influenza viral vaccine may be delivered to the subject intramuscularly, intramucosally, intranasally, subcutaneously, intratumorally, intradermally, transdermally, intravaginally, intraperitoneally, intrarectally, intra-articularly or intra-lymphatically, orally or 2023-048 intravenously. In some embodiments, administration may be by sublingual, buccal, intra-organ (e.g., intrasplenic), or inhaled routes. For intravenous, cutaneous or subcutaneous injection, or injection at the site of an infection, the vaccine composition may be in the form of a parenterally acceptable aqueous solution which has suitable pH, isotonicity and stability. Those of relevant skill in the art are well able to prepare suitable solutions using, for example, isotonic vehicles such as Sodium Chloride Injection, Ringer's Injection, or Lactated Ringer's Injection. Preservatives, stabilizers, buffers, antioxidants and / or other additives may be included, as required. In some embodiments, the influenza vaccine is administered peripherally to the subject. In some embodiments, multiple aliquots of the vaccine are administered peripherally to the subject in different locations. In some embodiments, the influenza vaccine is administered simultaneously or sequentially (either before or after) with a vaccine-enhancing agent. In some embodiments, the vaccine-enhancing agent is an angiotensin receptor blocker (ARB) or a beta blocker (BB). Exemplary vaccine-enhancing agents include losartan, telmisartan, irbesartan, azilsartan, candesartan, eprosartan, olmesartan, valsartan, propranolol, acebutolol, atenolol, betaxolol, bisoprolol, carteolol, carvedilol, esmolol, labetalol, metoprolol, nadolol, nebivolol, penbutolol, pindolol, propranolol, sotalol, timolol. In some embodiments, the vaccine-enhancing agent is selected from the group consisting of losartan and propranolol. In some embodiments, the vaccine- enhancing agent is losartan. In some embodiments, the vaccine-enhancing agent is propranolol. Suitable subjects include both avians and mammals. The term “avian” as used herein includes, but is not limited to, chickens, ducks, geese, quail, turkeys, pheasant, parrots, parakeets, and the like. The term “mammals” as used herein includes, but is not limited to, humans, non- human primates, bovines, ovines, caprines, equines, felines, canines, lagomorphs, etc. Human subjects include neonates, infants, juveniles, adults and geriatric subjects. Diagnostic methods In diagnostic development, the goal is to have an accurate test to detect a target of interest, whether that be a nucleic acid, antigen, or antibody. Several serological assays have been developed that use the influenza viral particle as an antigen to detect the present of antibodies against that pathogen in the host. Serological assays are important for the detection of antibodies against pathogens in the host. These assays provide information on previous exposure to an antigen 2023-048 and are used for the surveillance and prevalence of a pathogen within a population. A common serological platform is to use antigen from the pathogen to detect the presence of antibodies. The key to success with such approaches resides in the ability to balance the alterations required for antigen production with the preservation of key antigen epitopes similar to the native pathogen and maintain high diagnostic accuracy. Candidates produced by such a method would possess the native protein structures that are as close to natural structures in the intact pathogen as possible. The production of inactivated pathogen antigens uses methods such as heat and formalin, but the harsh treatments can lead to damage to key epitopes for antibody binding. Antigens are also produced using a bacterial system where specific antigens from the pathogen are recombinantly produced. These antigens are commonly pieces of the pathogen as opposed to the whole pathogen. Using smaller, more specific antigens allow for the detection of specific antibodies but does not allow the detection of multiple antibody subtypes and therefore reduces assay sensitivity. Moreover, these recombinant antigens are laborious and time consuming to produce. The technique typically requires specialized skill set and equipment. Provided herein is a method for producing whole pathogen antigen (i.e., inactivated viral particles) for use in a diagnostic assay, using a combination of UV light and riboflavin. The UV and riboflavin methodology utilizes whole pathogen for increased antibody attachment and the production process is much shorter. Additionally, the method is safe and does not need harsh inactivation methods or sophisticated equipment for production. The method can be used to rapidly develop indirect or capture format serological assay like ELISAs, lateral flow tests, and western blots. The method can be used with existing serological assays to improve sensitivity and reduce assay cost. Or it can be used for new assay development especially with newer multiplexing technologies. Lastly, the ease and low cost to produce inactivated antigen makes it useful in lower- income areas where the need for sensitive yet affordable diagnostic tests is critically needed. Thus, in some embodiments, influenza viral particles inactivated according to the methods disclosed herein may be used in diagnostic compositions and methods. For example, the inactivated influenza viral particles may be used to detect the presence of an anti-viral antibody (e.g., a neutralizing antibody) in a biological sample. The biological sample may be, for example, blood (e.g., whole blood, serum, or plasma), stool, urine, saliva, or swab specimens of the nostril, throat, cervix, or urethra. Because intact influenza viral particles are used, antibodies that bind to 2023-048 many different targets (i.e., different viral epitopes, such as HA or other influenza proteins, may be detected using a single assay. In some embodiments, an inactivated influenza viral particle is coupled to and / or immobilized on a substrate. The substrate may be biological, nonbiological, organic, inorganic, or a combination of any of these, existing as particles, strands, precipitates, gels, sheets, tubing, spheres, containers, capillaries, pads, slices, films, plates, slides, etc. The substrate may have any convenient shape, such as a disc, square, sphere, and a circle. The substrate may, in some embodiments, form a rigid support. In some embodiments, the substrate and its surface may be chosen to provide appropriate light-absorbing characteristics. For instance, the substrate may be a polymerized Langmuir Blodgett film, functionalized glass, Si, Ge, GaAs, GaP, SiO2, SiN4, modified silicon, or any one of a wide variety of polymers such as (poly)tetrafluoroethylene, (poly)vinylidenedifluoride, or combinations thereof. In some embodiments, the substrate may be a bead, a resin, a membrane, a fiber, a polymer, a matrix, a chip, a microplate or a tissue culture vessel. In some embodiments, the substrate is pre-treated before the inactivated influenza viral particle is coupled thereto. For example, the substrate may be treated with an enzyme, such as a DNAse, RNAse or protease. In some embodiments, the substrate may be coated with a polymer or a carbohydrate. In some embodiments, the substrate may be coated with a protein, such as an antibody, antibody fragment (e.g., Fab), or antibody derivative (e.g., a single chain variable fragment (scFv)). The inactivated viral particle (e.g., the inactivated influenza viral particle) may be coupled to the substrate using various different methods. For example, the inactivated viral particle may be reversibly or irreversibly coupled to the substrate. In some embodiments, the inactivated viral particle is coupled to the substrate via a linker. The linker may be a chemical or a protein linker. The chemical linker may be, for example, a carbohydrate linker, a polyether linker, a fatty acid linker, or a lipid linker. In some embodiments, the protein linker may comprise about 1 to about 50 amino acids. In some embodiments, the protein linker is a flexible linker (i.e., a linker that comprises small polar amino acids, including threonine, serine, and / or glycine). In some embodiments, the protein linker is not flexible (i.e., a linker that comprises one or more proline residues). 2023-048 In some embodiments, the inactivated influenza viral particles described herein may be used in a method for detecting the presence of an antibody in a biological sample. The antibody may be an antibody that binds to the viral particle (e.g., an influenza viral particle), such as a neutralizing antibody. In some embodiments, the method for detecting an antibody in a biological sample comprises contacting the biological sample with a virus particle (e.g., an influenza particle) that is coupled to a substrate. In some embodiments, the antibody binds to the virus particle that is coupled to the substrate, thereby immobilizing the antibody. In some embodiments, the method further comprises contacting the immobilized antibody with a second antibody, such as a detection antibody. The detection antibody may be coupled to, for example, a fluorophore, or to an enzyme (e.g., horseradish peroxidase (HRP)) capable of cleaving a substrate (e.g., a fluorescent substrate). In some embodiments, the inactivated influenza viral particles described herein may be used in an ELISA-based assay. An ELISA (enzyme-linked immunosorbent assay) is a plate-based assay technique designed for detecting and quantifying proteins, such as antibodies, in a biological sample. In an ELISA, an antigen (e.g., an inactivated influenza viral particle) is typically immobilized to a solid surface and then complexed with an antibody that is linked to an enzyme. Detection may be accomplished by measuring the activity of the reporter enzyme via incubation with the appropriate substrate to produce a measurable product. There are several different types of ELISAs commonly used, including direct ELISAs, indirect ELISAs, sandwich ELISAs, and competitive ELISAs. In some embodiments, an inactivated influenza particle is coupled to a substrate. The influenza particle is contacted with a biological sample comprising an antibody that binds to the influenza particle. A complex is formed between the antibody and the virus particle that is coupled to the substrate, thereby immobilizing the antibody. After the biological sample (including any unbound antibodies) is washed away, the antibody is contacted with a detection antibody. The binding of the antibody to the influenza particle is measured, for example, by detecting the amount of detection antibody bound. In some embodiments wherein the detection antibody is conjugated to an enzyme (e.g., an HRP), binding of the antibody to the influenza particle may be measured by measuring the amount of a fluorophore produced when an appropriate substrate is added to the sample. 2023-048 Immunogenic Compositions Comprising Inactivated Viral Particles Convalescent plasma therapy has long been used to treat or prevent viral and other infections. This therapy has been used against novel viruses that spread through communities with no natural immunity, where there are survivors, and where no vaccine and no effective antiviral treatment is available. Convalescent plasma therapy was first described during the 1918 Spanish influenza (H1N1) pandemic, and has since been used to treat diphtheria, measles, SARS, MERS, and Ebola. Convalescent plasma therapy involves obtaining plasma from a first subject that has recovered from a viral or other infection (i.e., a convalescent subject). The first subject’s plasma presumably contains antibodies against the virus or other pathogenic agent. Subsequently, the first subject’s plasma is administered to a second subject, in order to treat or prevent infection in the second subject. Several clinical studies have reported success using convalescent plasma therapy to treat or prevent various infections, but such data is often hard to interpret. Moreover, there are several issues which prevent widespread use of such therapy. For example, plasma obtained from each convalescent subject will contain a different titer of antibodies and may have different neutralizing potential. Therefore, it is difficult to predict a priori if a particular convalescent subject’s plasma will be effective when administered to a second subject. Additionally, the availability of convalescent plasma is limited by the number of convalescent subjects. During large pandemics or other periods of high demand, there may not be enough convalescent plasma to treat all subjects in need thereof. There is a need in the art for improved therapies that overcome the limitations of convalescent plasma therapy. Specifically, there is a need in the art for improved methods for producing antibodies against one or more viruses or other pathogens and use thereof to treat or prevent disease in a subject. The inactivated influenza viral particles described herein may be used in immunogenic compositions, to provoke an antibody response when administered to a host. The antibodies may then be recovered from the host and administered to subject in need thereof in order to treat or prevent a disease or disorder in the subject. In some embodiments, the compositions and methods described herein are used to treat or prevent infection by the influenza virus in a subject in need 2023-048 thereof. In some embodiments, the compositions and methods described herein may be used for convalescent plasma therapy. In some embodiments, an immunogenic composition comprises a polyclonal antibody that binds to an influenza viral particle, wherein the polyclonal antibody is produced by administering to a host an inactivated viral particle, wherein the inactivation is performed by contacting the viral particle with a dose of UV light in the presence of riboflavin. In some embodiments, the dose of UV light is about 100 Joules to about 1000 Joules. In some embodiments, the dose of UV light is about 100 Joules. Also provided herein are methods for treating or preventing a disease or disorder in a subject in need thereof, the method comprising administering to a subject in need thereof an effective amount of an immunogenic composition as described herein. In some embodiments, the inactivated viral particle is influenza, and the disease or disorder is influenza. In some embodiments, the immunogenic composition is administered intravenously to the subject. In some embodiments, the immunogenic composition is administered intramuscularly to the subject. In some embodiments, the subject is a human. In some embodiments, a method of producing a polyclonal antibody that binds to an influenza viral particle comprises generating an inactivated viral particle by contacting the influenza viral particle with a dose of UV light in the presence of riboflavin; administering the inactivated viral particle to a host, wherein the host produces a polyclonal antibody; and recovering the polyclonal antibody. In some embodiments, the viral particle is an influenza particle. In some embodiments, the host is a chicken, and the polyclonal antibody is recovered from an egg produced by the host. n some embodiments, the polyclonal antibody is recovered from the blood of the host. In some embodiments, the polyclonal antibody is recovered from B cells of the host. Also provided are polyclonal antibodies produced by the methods described herein. Also provided are methods for treating or preventing a disease or disorder in a subject in need thereof, the method comprising administering to a subject in need thereof an effective amount of a polyclonal antibody described herein. Also provided are methods for detecting the presence of an influenza viral particle in a subject in need thereof, the method comprising contacting a biological sample of the subject with a polyclonal antibody as described herein; and detecting binding between the polyclonal antibody 2023-048 and the influenza viral particle. In some embodiments, the biological sample is whole blood, serum, plasma, urine, saliva, lymph fluid, bile, cerebrospinal fluid, nasal mucus, or stool. In some embodiments, the polyclonal antibody is conjugated to a substrate. In some embodiments, the substrate is a bead, a chip, a slide or a dish. In some embodiments, the detecting step comprises contacting the polyclonal antibody with a secondary antibody that is conjugated to an enzyme or to a fluorophore. Methods for Producing Polyclonal Antibodies in a Host The compositions described herein, including the immunogenic compositions, can be used to provoke an immune response in a host. In some embodiments, a composition comprising an inactivated viral particle or other inactivated pathogen is administered to a host, in order to provoke an immune response in the host. The immune response may comprise, for example, production of antibodies against various different antigens on the inactivated viral particle or other inactivated pathogen. As used herein, the term “polyclonal antibodies” refers to antibodies that are secreted by different B cell lineages. In contrast, a monoclonal antibody comes from a single-cell lineage. A polyclonal antibody comprises a collection of immunoglobulin molecules that react against a specific antigen, each identifying a different epitope. Typically, when a viral particle or other pathogenic particle is administered to a host, the host produces a polyclonal antibody against the particle that was administered. The polyclonal antibody will typically include a mixture of antibodies produced by different B cell lineages, and each antibody may identify a different epitope. In some embodiments, a method of producing a polyclonal antibody that binds to an influenza viral particle comprises i) generating an inactivated influenza viral particle by contacting the influenza viral particle with a dose of UV light in the presence of riboflavin; ii) administering the inactivated influenza viral particle to a host, wherein the host produces a polyclonal antibody; and iii) recovering the polyclonal antibody. The inactivated viral particle or other pathogenic particle may be administered to the host by standard methods used in the art. For example, the inactivated particle may be administered intramuscularly, intramucosally, intranasally, subcutaneously, intratumorally, intradermally, transdermally, intravaginally, intraperitoneally, intrarectally, intra-articularly or intra- lymphatically, orally or intravenously. 2023-048 In some embodiments, the host is a mammal. In some embodiments, the host is a non- human primate, a bovine, an ovine, a caprine, an equine, a feline, a canine, a rodent or a lagomorph. The rodent may be, for example, a mouse, a rat, a guinea pig, or a hamster. In some embodiments, the host is a human. In some embodiments, the host is an avian. In some embodiments, the host is a chicken, a duck, a goose, a quail, a turkey, a pheasant, a parrot, or a parakeet. The polyclonal antibody may be recovered from a host in numerous different ways. For example, a blood sample (e.g., whole blood, serum, or plasma) containing the polyclonal antibody may be recovered from the host. In some embodiments, the antibody may be recovered from an immune cell producing an antibody (e.g., a B-cell) that is obtained from the host. In some embodiments, the antibody may be recovered from biological material produced by the host. For example, antibodies may be recovered from an egg (e.g., a chicken egg) produced by the host. In some embodiments, the antibodies may be isolated or purified after they are recovered from the host. In some embodiments, the antibodies are not isolated or purified after they are recovered from the host. In some embodiments, the host is a chicken, and the polyclonal antibody is recovered from an egg produced by the host. In some embodiments, the polyclonal antibody is recovered from the blood of the host. In some embodiments, the polyclonal antibody is recovered from B cells of the host. In some embodiments, about 1x105to about 1x108influenza viral particles are administered to a host in each administration. For example, about 1x105, about 5x105, about 1x106, about 5x106, about 1x107, about 5x107, or about 1x108influenza viral particles may be administered to a host per administration. In some embodiments, the administered dose is a split dose, wherein the total number of influenza viral particles for administration is divided into 2, 3, 4, 5, 6, 7, 8, 9, or 10 sub-doses. In some embodiments, about 10 to about 100 micrograms of influenza viral protein are administered to a host in each administration. In some embodiments, about 1 to about 100 picograms of influenza viral protein are administered to a host in each administration. In some embodiments, about 15 to about 50 picograms, or about 30 to about 40 picograms of influenza viral protein are administered to a host in each administration. For example, about 5, about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, or about 100 picograms of 2023-048 influenza viral protein may be administered to a host in each administration. In some embodiments, about 10 picograms of influenza viral protein are administered to a host in each administration. In some embodiments, about 11 picograms of influenza viral protein are administered to a host in each administration. In some embodiments, about 12 picograms of influenza viral protein are administered to a host in each administration. In some embodiments, about 13 picograms of influenza viral protein are administered to a host in each administration. In some embodiments, about 14 picograms of influenza viral protein are administered to a host in each administration. In some embodiments, about 15 picograms of influenza viral protein are administered to a host in each administration. In some embodiments, about 16 picograms of influenza viral protein are administered to a host in each administration. In some embodiments, about 17 picograms of influenza viral protein are administered to a host in each administration. In some embodiments, the administered dose is a split dose, wherein the total amount of influenza viral protein for administration is divided into 2, 3, 4, 5, 6, 7, 8, 9, or 10 sub-doses. One or more sub-dose may be administered to the host peripherally at different locations on the host’s body. Each sub-dose may be administered at approximately the same time, or administration of the sub-doses may be staggered. For example, sub-doses may be administered at intervals of 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, or 3 hours. In some embodiments, the composition may be administered once, or more than once to the host. In some embodiments, the influenza vaccine is administered once, twice, three times, four times, five times, six times, seven times, eight times, nine times, or ten times to the host. The composition may be administered to the host every day, about every 3 days, about every 7 days, about every fourteen days, about once per month, or about once per year. In some embodiments, the composition is administered at least once per week, at least every two weeks, or at least once every six months. In some embodiments, the composition is administered once, twice, three times, four times, five times, six times, seven times, eight times, nine times, ten times, twelve times, fifteen times, twenty times, or twenty-five times in a year. In some embodiments, a first dose (e.g., a prime dose) of the composition is administered, followed by a second dose (e.g., a boost dose) to the host. In some embodiments, the second dose is administered about 1 week, about 2 weeks, about 3 weeks, about 4 weeks, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, or about 1 year after the first dose. In some embodiments, the amount of influenza viral protein in the first dose is greater than the 2023-048 amount of viral protein in the second dose. For example, the amount of viral protein may be about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or about 100% greater than the amount of viral protein in the first dose. In some embodiments, the amount of viral protein in the first dose is less than the amount of influenza viral protein in the second dose. For example, the amount of influenza viral protein may be about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or about 100% less than the amount of influenza viral protein in the first dose. In some embodiments, the amount of viral protein in the first dose is about the same as the amount of influenza viral protein in the second dose. In some embodiments, a first inactivated influenza composition and a second inactivated influenza composition are administered to the host. In some embodiments, the second inactivated influenza composition is administered after the first inactivated influenza composition to boost the immune response. In some embodiments, immune response in the subject is monitored between administration of the first composition and the second composition. In some embodiments, the second composition is administered when it is determined that the host has not exhibited a satisfactory immune response following administration of the first composition. In some embodiments, the composition is administered simultaneously or sequentially (either before or after) with an immune-enhancing agent. In some embodiments, the immune- enhancing agent is an angiotensin receptor blocker (ARB) or a beta blocker (BB). Exemplary immune-enhancing agents include losartan, telmisartan, irbesartan, azilsartan, candesartan, eprosartan, olmesartan, valsartan, propranolol, acebutolol, atenolol, betaxolol, bisoprolol, carteolol, carvedilol, esmolol, labetalol, metoprolol, nadolol, nebivolol, penbutolol, pindolol, propranolol, sotalol, and timolol. In some embodiments, the immune-enhancing agent is selected from the group consisting of losartan and propranolol. In some embodiments, the immune- enhancing agent is losartan. In some embodiments, the immune-enhancing agent is propranolol. In some embodiments, a method for administering an immunogenic composition to a host comprises administering a composition comprising inactivated viral particles or other inactivated particles to the host. Administration of an immunogenic composition (e.g., a composition comprising inactivated influenza viral particles) may elicit an immune response in the host. In some embodiments, the immune response may include one or more of the following: (i) upregulation of immunoglobulin expression (e.g., IgG, IgM, IgA, IgE), (ii) T-cell activation, (iii) 2023-048 modulation of innate immune cells (e.g., myeloid cells), and (iv) revival of “exhausted” T-Cell populations. Also provided are polyclonal antibodies produced according to the methods described herein, and polyclonal antibodies produced using the immunogenic compositions described herein. The polyclonal antibodies may comprise, for example, IgG, IgM, IgA, IgY, or IgE, or mixtures thereof. In some embodiments, the polyclonal antibodies bind to a viral particle or other pathogen. In some embodiments, the polyclonal antibodies bind to the same viral particle or pathogen in the subject as was used to produce the polyclonal antibody in the host. All patents, patent applications, references, and journal articles cited in this disclosure are expressly incorporated herein by reference in their entireties for all purposes. The invention now being generally described will be more readily understood by reference to the following examples, which are included merely for the purposes of illustration of certain embodiments of the present invention. The examples are not intended to limit the invention, as one of skill in the art would recognize from the above teachings and the following examples that other techniques and methods can satisfy the claims and can be employed without departing from the scope of the claimed invention. Indeed, while this invention has been particularly shown and described with references to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention encompassed by the appended claims. EXAMPLES Described below are various studies evaluating a photochemical process for inactivation of viral particles, including influenza, and use of an inactivated influenza whole virion for prevention of influenza infection. These studies demonstrate the ability of this process to inactivate influenza virus via a specific, targeted guanine base modification. This work also demonstrated the ability of products made via this method to induce a potent immune response to vaccination. This response triggered both Th1 and Th2 type immune pathways, leading to generation of neutralizing antibodies and cellular responses capable of protecting vaccinated animals against intranasal challenge with 105pfu influenza. The data also shows a vaccine candidate for influenza produced by this method (SolaVax™) is effective in providing protection against challenge infection in a sensitive hamster model. The use of this inactivation / viral production methodology may afford a means to rapidly 2023-048 produce vaccine candidates in response to both emergent and existing disease threats. Given the nature of the photosensitizer (riboflavin) and equipment utilized in this setting, such an approach may afford a facile method to prepare vaccine candidates in a logistically practical and cost- effective manner that avoids issues associated with current methods for production of inactivated vaccines. This more selective method of nucleic acid modification, without extensive protein alteration, which is known to occur with current inactivation approaches, may also result in more effective vaccination at lower immunogen dose, thus facilitating vaccine distribution and availability in diverse regions of the global community. Example 1: Retention of HA Protein. As shown in Figure 1A, the InDevR Vaxarray platform was used to analyze the preservation and potency of the HA antigen (SEQ ID NO.1) for binding to antibodies. Applicants used the Vaxarray seasonal influenza monovalent HA assay and compared live virus (H1N1 A / California / 07 / 2009 strain) to inactivate material treated by SolaVAX (Mirasol) or by formalin. The SolaVAX method was comparable in HA reactivity compared to live virus indicating the treatment preserved HA antigenicity. The SolaVAX method had better preservation of the HA antigen compared to formalin treatment. As shown in Figure 1A, retention of hemagglutinin antigen (HA) levels in H1N1 after preparation by SolaVAX inactivation (orange) and formalin treatment (pink), compared to H1N1 stock control (gray). Viral protein measured with VaxArray system using flu antigen standard. As demonstrated, influenza material inactivated by SolaVAX provided 70-80% retention of HA activity, as compared to 40-45% after inactivation by formalin Example 2: Mouse Antibody Generation Post-Vaccination with SolaVAX-INF. As shown in Figure 2, images of neutralization assay plates demonstrating the production of neutralizing antibodies by the high and low dose SolaVAX groups. Mouse 34 from the high dose group and mouse 41 from the low dose group show a titer of 1:320 by PRNT90 cutoff. Example 3: Neutralizing antibody response in mice 56 days after vaccination with inactivated SolaVAX vaccine. As shown in Figure 3, female ICR mice (N=5 / group) were vaccinated with either SolaVAX, formalin inactivated, or live virus (5e5 pfu / ml). The inactivated influenza vaccines were derived from H1N1 A / California / 07 / 2009 strain and were formulated as 40ug, 20ug, or 10ug total protein per dose. All mice received a prime dose vaccination intramuscularly and then a booster dose 21 days later. At 56 days post prime dosing, the mice were humanely euthanized and terminal 2023-048 blood collected to determine neutralizing antibody response by microneutralization assays. Antibody titers were recorded as the reciprocal of the highest dilution in which >90% of virus was neutralized. BPL= Beta-propiolactone. Antibodies were detected in all vaccinated groups. A dose response was observed with the SolaVAX and formalin inactivated groups. While the live control had a stronger response than the SolaVAX groups, the live control received a higher dose of virus compared to the groups. SolaVAX formulated at 20 and 10 ug doses had a higher antibody response compared to the formalin 20 and 10 ug groups. Example 4: Neutralizing antibody response in mice 56 days after vaccination with inactivated SolaVAX vaccine. As shown in Figure 4, female ICR mice (N=5 / group) were vaccinated with either SolaVAX, formalin inactivated, or live virus (5e5 pfu / ml). The inactivated influenza vaccines are derived from H1N1 A / California / 07 / 2009 strain and were formulated as 40mg, 20mg, or 10mg total protein per dose. All mice received a prime dose vaccination intramuscularly and then a booster dose 21 days later. At 56 days post prime dosing, the mice were humanely euthanized and terminal blood collected to determine neutralizing antibody response by microneutralization assays. Antibody titers were recorded as the reciprocal of the highest dilution in which >90% of virus was neutralized. Applicants detected a dose response to the SolaVAX inactivated material when used to vaccinate mice. Mice vaccinated with SolaVAX material at a 10ug dose responded with a higher neutralizing antibody titer when compared to the traditional formalin inactivated vaccine. Example 5: In vitro inactivation of influenza virions. As shown in Figure 5, viral loads in respiratory tissues from hamster after challenge with live virus. Oropharyngeal swabs were taken on 1, 2, and 3 days post infection (dpi). Viral titers of swabs collected from hamsters vaccinated via subcutaneous (SQ; A) and intramuscular (IM; B) were determined by plaque assay. The presence of infectious virus was also determined 3 dpi in turbinate’s (C), trachea (D), right cranial lung lobe (E), and right caudal lung lobe (F). Data shows mean + / - standard deviation. Limit of detection is denoted as horizontal dotted line. Asterisks indicate statistically significant difference in viral titers between control and vaccinated group (****p<0.0001, ***p<0.001, **p<0.01, *p<0.05). Example 6: Materials and Methods. 2023-048 Animals: Six- to eight-week-old outbred (ICR) female mice (50 total) will be housed in cages covered with barrier filters in an approved biosafety level 2 animal facility maintained by Colorado State University, Fort Collins, Colorado. All experiments will be performed using experimental protocols approved by the Institutional Animal Care and Use Committee (IACUC), Colorado State University and will follow National Institutes of Health and United States Department of Agriculture guidelines.5 mice vaccinated at highest 40 ug of live virus Inactivated Virions Production Design: Whole virion inactivated vaccines will be produced in the IDRC via 3 different inactivation methods with H1N1 influenza A virus (A / California / 07 / 2009) in a BSL-2 setting. Three groups of mice (N=15 per group) will be administered 0.1ml of vaccine intramuscularly (IM) on days 0 and 21 with 3 different doses of vaccines (5 hamsters per dose, per group). A fourth group of mice (N=5) will be vaccinated with live virus serve as a control group. To test for antibody production, blood will be collected by facial vein puncture on days 0, 21, and 56 post-prime immunization. Additional bleeding days may be added at the discretion of the PI for this study. Sera will be stored at -80C until assay. Vaccination schedules for this study are as follows: 1. 15 mice: βPL-inactivated vaccine a. 5 mice: vaccinated with 40 ug material b. 5 mice: vaccinated with 20 ug material c. 5 mice: vaccinated with 10 µg material 2. 15 mice: Formalin-inactivated vaccine a. 5 mice: vaccinated with 40 ug material b. 5 mice: vaccinated with 20 ug material c. 5 mice: vaccinated with 10 µg material 3. 15 mice: SolaVAX-inactivated vaccine a. 5 mice: vaccinated with 40 ug material b. 5 mice: vaccinated with 20ug material c. 5 mice: vaccinated with 10 µg material 4. 5 mice: Live virus vaccination (control group) Vaccine Administration Vaccination Grp 1A-C βPL-Inactivated IM Day 0, Day 21 Grp 2A-C Formalin- IM Day 0, Day 21 Inactivated Grp 3A-C SolaVAX IM Day 0, Day 21 Grp 4 (ctrl) Live Virus IM Day 0 2023-048 Virus Preparation: Virus will be grown in the allantoic cavity of 10-day–old embryonated hens’ eggs using standard intraallantoic inoculation. Virus as allantoic fluid will be harvested 3 days post-inoculation, pooled and frozen in 10 ml aliquots. Viral titer will be determined via PA on MDCK cells prior to use. Viral Inactivation: Vaccine material for Group 1 will be produced by incubating H1N1 virus stock with β-PL at a final concentration of 0.1% BPL at 4°C for 16-24 hours. Β-PL will be removed post-inactivation by tangential flow filtration (TFF). Vaccine material for Group 2 will be produced by incubating H1N1 virus stock with Formalin at a final concentration of 0.1% Formalin at 37°C for 16-24 hours. Formalin will be removed post-inactivation by TFF. Vaccine material for Group 3 will be produced by a photoinactivation process using riboflavin and UV light (SolaVAX). Post-inactivation material will be processed by TFF. Samples of inactivated material may be retained for host-cell protein, host-cell DNA, and other analyses. Samples will be stored at ≤-65°C until time of testing. Neutralizing Antibody Assays: Sera will be heat inactivated at 56°C for 30 minutes. Assays for virus-specific neutralizing antibodies will be performed on serial 2-fold diluted samples of each serum using a microneutralization test and starting at a serum dilution of 1:5. The serum:virus mixtures will be incubated for 60 minutes at 37°C in 5% CO2; then 100 ^L of each mixture will be inoculated into recently confluent MDCK cells in multi-well plates for 18-20 hours at 37°C in 5% CO2. Particle Counts and Antigenicity Assays: The number of virion particles present in each batch of inactivation material (after TFF) will be quantified using the Virocyte Virus Counter Platform (Sartorius). These data will be used to prepare vaccine material for each inactivation method that have equal numbers of virus particles per dose tested. The potency of the hemagglutinin (HA), neuraminidase (NA) and nucleoprotein (NP) antigens in the inactivated material will be characterized using the VaxArray Platform (InDevR). These data will then be compared to the neutralization response observed in the inoculated hamsters. Statistical Analysis: Neutralizing antibody titers, viral particle counts, levels of HA, NA and NP protein will be averaged for each data set. Comparisons will be conducted using parametric and nonparametric statistics as indicated. DEFINITIONS The following terms are used in the description herein and the appended claims: 2023-048 Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. The terminology used in the detailed description herein is for the purpose of describing particular embodiments only and is not intended to be limiting. The singular forms “a,” “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. Furthermore, the term “about” as used herein when referring to a measurable value such as an amount, dose, time, temperature, and the like, is meant to encompass variations of ± 20%, ± 10%, ± 5%, ± 1%, ± 0.5%, or even ± 0.1% of the specified amount. Also as used herein, “and / or” refers to and encompasses any and all possible combinations of one or more of the associated listed items, as well as the lack of combinations when interpreted in the alternative (“or”). As used herein, the terms “reduce,” “reduces,” “reduction” and similar terms mean a decrease of at least about 10%, about 15%, about 20%, about 25%, about 35%, about 50%, about 75%, about 80%, about 85%, about 90%, about 95%, about 97% or more. As used herein, the terms “enhance,” “enhances,” “enhancement” and similar terms indicate an increase of at least about 10%, about 15%, about 20%, about 25%, about 50%, about 75%, about 100%, about 150%, about 200%, about 300%, about 400%, about 500% or more. As used herein, the term “vaccine” is typically understood to be a prophylactic or therapeutic material providing at least one antigen or antigenic function. The antigen or antigenic function may stimulate the body's adaptive immune system to provide an adaptive immune response. The terms “subject,” “individual,” and “patient” are used interchangeably herein to refer to a vertebrate, such as a mammal. The mammal may be, for example, a mouse, a rat, a rabbit, a cat, a dog, a pig, a sheep, a horse, a non-human primate (e.g., cynomolgus monkey, chimpanzee), or a human. As used herein, the term “inactivated” refers to a pathogen, such as a virus or microbe, or a vaccine comprising microbes, that has been treated and / or modified so that the pathogen do not have disease-producing capacity. In some embodiments, an inactivated vaccine comprises microbes that have been killed by physical and / or chemical processes. In some embodiments, the inactivated microbes do not replicate in a subject. In some embodiments, the inactivated pathogen 2023-048 are alive, while in some embodiments, the inactivated microbes are dead. In a preferred embodiment, the inactivated pathogen is generated by the SolaVAX process. As used herein, the term “attenuated,” the term “live vaccine” or “attenuated vaccine” refers to a vaccine containing a live viral active ingredient. In addition, “attenuation” means that the toxicity of a living pathogen is artificially weakened, and it does not cause disease in the body by mutating genes involved in the essential metabolism of pathogens, but only stimulates the immune system to induce immunity. Viral attenuation can be achieved by irradiation, chemical treatment, or n by high-order continuous subculture in vitro, a / k / a serial passage. Attenuation can also be achieved by making clear genetic changes, for example by specific deletions of viral sequences known to provide toxicity or by insertion of sequences into the genome. As used herein, the term “inactivated / attenuated” or alternatively “attenuated / inactivated” refers to a pathogen, such as an ASFV particle, that has been attenuated and further inactivated, preferably through a SolaVAX process. As used herein, the term “SolaVAX” refers to a vaccine comprising a pathogen particle, including a viral, bacterial or pathogen or fragments thereof, which have been inactivated using riboflavin and UV light as described herein. The systems, methods and processes that encompass SolaVAX are described by Goodrich et al., PCT / US2021 / 021190 and PCT / US2021 / 053160, entitled, the entire specifications, claims and figures related to the inactivation of pathogen particles using UV radiation in the presence of riboflavin is hereby being incorporated by reference.) The terms “pre-SolaVAX” and “post-SolaVAX” refer to pathogen preparations before and after inactivation, respectively, using riboflavin and UV light. In a preferred embodiment, the pathogen is attenuated prior to inactivation by application of SolaVAX treatment. By the terms “treat,” “treating” or “treatment of” (and grammatical variations thereof) it is meant that the severity of the subject's condition is reduced, at least partially improved or stabilized and / or that some alleviation, mitigation, decrease or stabilization in at least one clinical symptom is achieved and / or there is a delay in the progression of the disease or disorder. The terms “prevent,” “preventing” and “prevention” (and grammatical variations thereof) refer to prevention and / or delay of the onset of a disease, disorder and / or a clinical symptom(s) in a subject and / or a reduction in the severity of the onset of the disease, disorder and / or clinical symptom(s) relative to what would occur in the absence of the methods of the disclosure. The prevention can be complete, e.g., the total absence of the disease, disorder and / or clinical 2023-048 symptom(s). The prevention can also be partial, such that the occurrence of the disease, disorder and / or clinical symptom(s) in the subject and / or the severity of onset is less than what would occur in the absence of the present disclosure. “Effective amount,” or “Therapeutically Effective Amount” as used herein refers to an amount that, when administered to a subject for treating or preventing a disease (e.g., a viral infection), or at least one of the clinical symptoms of a disease, is sufficient to affect such treatment or prevention of the disease or symptom thereof. The “effective amount” may vary depending, for example, on the disease and / or symptoms of the disease, severity of the disease and / or symptoms of the disease or disorder, the age, weight, and / or health of the subject to be treated, and the judgment of the prescribing physician. An appropriate amount in any given instance may be ascertained by those skilled in the art or capable of determination by routine experimentation. When used herein to refer to an amount, the term “viral protein” refers to the total amount of viral protein measured in a vaccine preparation using, for example, a standard assay to measure protein content. In the context of the present invention “antigen” refers typically to a substance which may be recognized by the immune system, preferably by the adaptive immune system, and is capable of triggering an antigen-specific immune response, e.g., by formation of antibodies and / or antigen- specific T cells as part of an adaptive immune response. Typically, an antigen may be or may comprise a peptide or protein which may be presented by the MHC to T-cells. In the sense of the present invention an antigen may be the product of translation of a provided nucleic acid molecule, preferably an mRNA as defined herein. In this context, fragments, variants and derivatives of peptides and proteins comprising at least one epitope are understood as antigen. In a preferred embodiment, an antigen may preferably be an antigen related to the ASFV. Epitope (also called “antigen determinant”“): T cell epitopes or parts of the proteins in the context of the present invention may comprise fragments preferably having a length of about 6 to about 20 or even more amino acids, e.g. fragments as processed and presented by MHC class I molecules, preferably having a length of about 8 to about 10 amino acids, e.g.8, 9, or 10, (or even 11, or 12 amino acids), or fragments as processed and presented by MHC class II molecules, preferably having a length of about 13 or more amino acids, e.g.13, 14, 15, 16, 17, 18, 19, 20 or even more amino acids, wherein these fragments may be selected from any part of the amino acid sequence. These fragments are typically recognized by T cells in form of a complex consisting of 2023-048 the peptide fragment and an MHC molecule. B cell epitopes are typically fragments located on the outer surface of (native) protein or peptide antigens as defined herein, preferably having 5 to 15 amino acids, more preferably having 5 to 12 amino acids, even more preferably having 6 to 9 amino acids, which may be recognized by antibodies, i.e., in their native form. In a preferred embodiment, an antigen may preferably be an epitope related to one or more antigens of the ASFV. Such epitopes of proteins or peptides may furthermore be selected from any of the herein mentioned variants of such proteins or peptides, and preferably from ASFV. In this context antigenic determinants can be conformational or discontinuous epitopes which are composed of segments of the proteins or peptides as defined herein that are discontinuous in the amino acid sequence of the proteins or peptides as defined herein but are brought together in the three- dimensional structure or continuous or linear epitopes which are composed of a single polypeptide chain. The term “expression,” as used herein, or “expression of a coding sequence” (for example, a gene or a transgene) refer to the process by which the coded information of a nucleic acid transcriptional unit (including, e.g., genomic DNA or cDNA) is converted into an operational, non- operational, or structural part of a cell, often including the synthesis of a protein. Gene expression can be influenced by external signals; for example, exposure of a cell, tissue, or organism to an agent that increases or decreases gene expression. Expression of a gene can also be regulated anywhere in the pathway from DNA to RNA to protein. Regulation of gene expression occurs, for example, through controls acting on transcription, translation, RNA transport and processing, degradation of intermediary molecules such as mRNA, or through activation, inactivation, compartmentalization, or degradation of specific protein molecules after they have been made, or by combinations thereof. Gene expression can be measured at the RNA level or the protein level by any method known in the art, including, without limitation, Northern blot, RT-PCR, Western blot, or in vitro, in situ, or in vivo protein activity assay(s). The term “nucleic acid” or “nucleic acid molecules” include single- and double-stranded forms of DNA; single-stranded forms of RNA; and double-stranded forms of RNA (dsRNA). The term “nucleotide sequence” or “nucleic acid sequence” refers to both the sense and antisense strands of a nucleic acid as either individual single strands or in the duplex. The term “ribonucleic acid” (RNA) is inclusive of iRNA (inhibitory RNA), dsRNA (double stranded RNA), siRNA (small interfering RNA), mRNA (messenger RNA), miRNA (micro-RNA), hpRNA (hairpin 2023-048 RNA), tRNA (transfer RNA), whether charged or discharged with a corresponding acetylated amino acid), and cRNA (complementary RNA). The term “deoxyribonucleic acid” (DNA) is inclusive of cDNA, genomic DNA, and DNA-RNA hybrids. The terms “nucleic acid segment” and “nucleotide sequence segment,” or more generally “segment,” will be understood by those in the art as a functional term that includes both genomic sequences, ribosomal RNA sequences, transfer RNA sequences, messenger RNA sequences, operon sequences, and smaller engineered nucleotide sequences that encoded or may be adapted to encode, peptides, polypeptides, or proteins. The term “gene” or “sequence” refers to a coding region operably joined to appropriate regulatory sequences capable of regulating the expression of the gene product (e.g., a polypeptide or a functional RNA) in some manner. A gene includes untranslated regulatory regions of DNA (e.g., promoters, enhancers, repressors, etc.) preceding (up-stream) and following (down-stream) the coding region (open reading frame, ORF) as well as, where applicable, intervening sequences (i.e., introns) between individual coding regions (i.e., exons). The term “structural gene” as used herein is intended to mean a DNA sequence that is transcribed into mRNA which is then translated into a sequence of amino acids characteristic of a specific polypeptide. It should be noted that any reference to a SEQ ID, or sequence specifically encompasses that sequence, as well as all corresponding sequences that correspond to that first sequence. For example, for any amino acid sequence identified, the specific specifically includes all compatible nucleotide (DNA and RNA) sequences that give rise to that amino acid sequence or protein, and vice versa. The term “peptide” or “protein” is a polymer of amino acid monomers. Usually, the monomers are linked by peptide bonds. The term “peptide” does not limit the length of the polymer chain of amino acids. In some embodiments of the present invention a peptide may for example contain less than 50 monomer units. Longer peptides are also called polypeptides, typically having 50 to 600 monomeric units, more specifically 50 to 300 monomeric units. “Pharmaceutical compositions” are compositions that include an amount (for example, a unit dosage) of the disclosed compound(s) together with one or more non-toxic pharmaceutically acceptable additives, including carriers, diluents, and / or optionally other biologically active ingredients. Such pharmaceutical compositions can be prepared by standard pharmaceutical formulation techniques such as those disclosed in Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pa. (19th Edition). In one embodiment, a pharmaceutical composition of 2023-048 the invention may include a quantity of HIV-1, and a pharmaceutically acceptable carrier, such as a pharmaceutically acceptable excipient or carriers Such pharmaceutical compositions / formulations are useful for administration to a subject, in vivo or ex vivo. Pharmaceutical compositions and formulations include carriers or excipients for administration to a subject. As used herein the terms “pharmaceutically acceptable” and “physiologically acceptable” mean a biologically compatible formulation, gaseous, liquid, or solid, or mixture thereof, which is suitable for one or more routes of administration, in vivo delivery, or contact. Such formulations include solvents (aqueous or non-aqueous), solutions (aqueous or non- aqueous), emulsions (e.g., oil-in-water or water-in-oil), suspensions, syrups, elixirs, dispersion and suspension media, coatings, isotonic and absorption promoting or delaying agents, compatible with pharmaceutical administration or in vivo contact or delivery. Aqueous and non-aqueous solvents, solutions and suspensions may include suspending agents and thickening agents. Such pharmaceutically acceptable carriers include tablets (coated or uncoated), capsules (hard or soft), microbeads, powder, granules, and crystals. Supplementary active compounds (e.g., preservatives, antibacterial, antiviral, and antifungal agents) can also be incorporated into the compositions. The formulations may, for convenience, be prepared or provided as a unit dosage form. In general, formulations are prepared by uniformly and intimately associating the active ingredient with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product. For example, a tablet may be made by compression or molding. Compressed tablets may be prepared by compressing, in a suitable machine, an active ingredient in a free-flowing form such as a powder or granules, optionally mixed with a binder, lubricant, inert diluent, preservative, surface-active or dispersing agent. Molded tablets may be produced by molding, in a suitable apparatus, a mixture of powdered compound moistened with an inert liquid diluent. The tablets may optionally be coated or scored and may be formulated so as to provide a slow or controlled release of the active ingredient therein. Pharmaceutical formulations and delivery systems appropriate for the compositions and methods of the invention are known in the art (see, e.g., Remington: The Science and Practice of Pharmacy (2003) 20.sup.th ed., Mack Publishing Co., Easton, Pa.; Remington's Pharmaceutical Sciences (1990) 18.sup.th ed., Mack Publishing Co., Easton, Pa.; The Merck Index (1996) 12.sup.th ed., Merck Publishing Group, Whitehouse, N.J.; Pharmaceutical Principles of Solid Dosage Forms (1993), Technonic Publishing Co., Inc., Lancaster, Pa.; Ansel and Stoklosa, 2023-048 Pharmaceutical Calculations (2001) 11.sup.th ed., Lippincott Williams & Wilkins, Baltimore, Md.; and Poznansky et al., Drug Delivery Systems (1980), R. L. Juliano, ed., Oxford, N.Y., pp. 253-315). For example, pharmaceutical compositions can optionally be formulated to be compatible with a particular route of administration. Exemplary routes of administration include administration to a biological fluid, an immune cell (e.g., T or B cell) or tissue, mucosal cell or tissue (e.g., mouth, buccal cavity, labia, nasopharynx, esophagus, trachea, lung, stomach, small intestine, vagina, rectum, or colon), neural cell or tissue (e.g., ganglia, motor or sensory neurons) or epithelial cell or tissue (e.g., nose, fingers, ears, cornea, conjunctiva, skin or dermis). Thus, pharmaceutical compositions include carriers (excipients, diluents, vehicles, or filling agents) suitable for administration to any cell, tissue, or organ, in vivo, ex vivo (e.g., tissue or organ transplant) or in vitro, by various routes and delivery, locally, regionally, or systemically. Exemplary routes of administration for contact or in vivo delivery of a target inhibitor, is a dosage of the compound that is sufficient to achieve a desired therapeutic effect, such as can optionally be formulated include inhalation, respiration, intubation, intrapulmonary instillation, oral (buccal, sublingual, mucosal), intrapulmonary, rectal, vaginal, intrauterine, intradermal, topical, dermal, parenteral (e.g., subcutaneous, intramuscular, intravenous, intradermal, intraocular, intratracheal and epidural), intranasal, intrathecal, intraarticular, intracavity, transdermal, iontophoretic, ophthalmic, optical (e.g., corneal), intraglandular, intraorgan, and intralymphatic. The invention encompasses isolated or substantially purified pathogens, such as virions, bacterium or constituents thereof. In one example, “isolated” or “purified” influenza virions or constituents thereof, are substantially or essentially free from components that normally accompany or interact with influenza virions or constituents thereof as found in its naturally occurring environment.

[0002] 2023-048 Table 1: Exemplary influenza Strains and Isolates

[0003] 2023-048 SEQUENCE LISTING SEQ ID NO.1 Amino Acid HA Protein Influenza A virus (A / California / 07 / 2009(H1N1)) MKAILVVLLYTFATANADTLCIGYHANNSTDTVDTVLEKNVTVTHSVNLLEDKHNGKLCKLRGV APLHLGKCNIAGWILGNPECESLSTASSWSYIVETPSSDNGTCYPGDFIDYEELREQLSSVSSF ERFEIFPKTSSWPNHDSNKGVTAACPHAGAKSFYKNLIWLVKKGNSYPKLSKSYINDKGKEVLV LWGIHHPSTSADQQSLYQNADAYVFVGSSRYSKKFKPEIAIRPKVRDQEGRMNYYWTLVEPGDK ITFEATGNLVVPRYAFAMERNAGSGIIISDTPVHDCNTTCQTPKGAINTSLPFQNIHPITIGKC PKYVKSTKLRLATGLRNIPSIQSRGLFGAIAGFIEGGWTGMVDGWYGYHHQNEQGSGYAADLKS TQNAIDEITNKVNSVIEKMNTQFTAVGKEFNHLEKRIENLNKKVDDGFLDIWTYNAELLVLLEN ERTLDYHDSNVKNLYEKVRSQLKNNAKEIGNGCFEFYHKCDNTCMESVKNGTYDYPKYSEEAKL NREEIDGVKLESTRIYQILAIYSTVASSLVLVVSLGAISFWMCSNGSLQCRICI

Claims

2023-048 CLAIMS What is claimed is:

1. A method for inactivating an influenza particle, the method comprising contacting the influenza particle with a dose of UV light in the presence of riboflavin.

2. The method claim 1, wherein the dose of UV light is about 100 Joules to about 1000 Joules.

3. The method of claim 1, wherein the dose of UV light is about 100 Joules.

4. The method of claim 1, wherein the method comprises altering a nucleic acid of the influenza particle.

5. The method of claim 4, wherein the method comprises selectively oxidizing one or more guanine bases in the nucleic acid.

6. The method of claim 5, wherein the UV light selectively oxidizes about 1 to about 30 guanine bases in the nucleic acid of the influenza particle.

7. The method of claim 5, wherein the UV light selectively oxidizes about 20 guanine bases in the nucleic acid of the influenza particle.

8. The method of claim 4, wherein the influenza particle is selected from: influenza A, influenza B, influenza C, H1N1, H2N2, H3N1, H3N2, H3N8, H5N1, H7N1, H7N7, H1N2, H9N2, H7N2, H7N3, and H10N7.

9. The method of claim 4, wherein the influenza particle is selected from: − A / California / 07 / 2009, or an influenza particle having a genome sequence with about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% sequence identity to the genome of A / California / 07 / 2009; − B / Austria / 1359417 / 2021, or an influenza particle having a genome sequence with about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% sequence identity to the genome of B / Austria / 1359417 / 2021;2023-048 − B / Phuket / 3073 / 2013, or an influenza particle having a genome sequence with about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% sequence identity to the genome of B / Phuket / 3073 / 2013; − A / Wisconsin / 67 / 2022, or an influenza particle having a genome sequence with about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% sequence identity to the genome of A / Wisconsin / 67 / 2022; or − A / Darwin / 6 / 2021, or an influenza particle having a genome sequence with about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% sequence identity to the genome of A / Darwin / 6 / 2021.

10. The method of claim 4, wherein the influenza particle comprises an influenza particle having a hemagglutinin (HA) protein according to SEQ ID NO.

1.

11. The method of claim 4, wherein the influenza particle comprises an influenza particle having a hemagglutinin (HA) protein selected from: an HA protein according to SEQ ID NO. 1, or a sequence with about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97% 12. The method of claim 4, wherein the influenza particle comprises an influenza particle having a hemagglutinin (HA) protein selected from: an HA protein according to SEQ ID NO. 1, or a sequence with about 1 to about 100, about 100 to about 250, or about 250 or about 500 or more nucleic acid substitutions relative to the nucleotide sequence that encodes the HA protein according to SEQ ID NO.

1.

13. The method of claim 1, wherein the method does not comprise substantially altering the structure of antigens on the surface of the influenza particle.

14. The method of claim 1, wherein the inactivated influenza particle is not capable of replicating in a cell.2023-048 15. The method of claim 1, wherein the inactivated influenza particle is not capable of causing disease in a subject.

16. A vaccine composition comprising an influenza particle inactivated according to any one of claims 1-15.

17. The vaccine composition of claim 16, wherein the composition comprises about 1 to about 100 picograms of influenza protein.

18. The vaccine composition of claim 16, wherein the composition comprises about 15 to about 50 picograms of influenza protein.

19. The vaccine composition of claim 16, wherein the composition comprises about 35 picograms of influenza protein.

20. The vaccine composition of any one of claims 16-19, wherein the composition comprises a pharmaceutically acceptable carrier or excipient.

21. A method for treating or preventing a viral infection in a subject in need thereof, the method comprising administering to the subject an effective amount of the vaccine composition of any one of claims 16-20.

22. The method of claim 21, wherein the subject is a mammal.

23. The method of claim 22, wherein the subject is a human.

24. The method of any one of claims 21-23, wherein the vaccine is administered intramuscularly.

25. The method of any one of claims 21-23, wherein the vaccine is administered subcutaneously.

26. The method of any one of claims 21-25, wherein a first vaccine composition and a second vaccine composition are administered to the subject.2023-048 27. The method of claim 26, wherein the amount of viral protein in the first vaccine composition is greater than the amount of viral protein in the second vaccine composition.

28. The method of claim 26, wherein the amount of viral protein in the first vaccine composition is less than the amount of viral protein in the second vaccine composition.

29. The method of claim 26, wherein the amount of viral protein in the first vaccine composition is about the same as the amount of viral protein in the second vaccine composition.

30. The method of any one of claims 26-29, wherein the second vaccine composition is administered about 1 week, about 2 weeks, about 3 weeks, about 4 weeks, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, or about 1 year after the first vaccine composition.

31. The method of claim 30, wherein the second vaccine composition is administered about 3 weeks after the first vaccine composition.

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