Pentavalent and octavalent influenza virus immunogens, compositions and methods of use thereof

Abstract

Provided are an immunogenic multivalent (e.g., pentavalent or octavalent) composition, vaccine, and formulations thereof, composed of five or eight, isolated, non-naturally occurring, immunogenic antigens derived from influenza viruses that are capable of eliciting a broadly reactive immune response, e.g., a broadly reactive neutralizing antibody response directed against influenza virus antigens, following introduction into a subject. Also provided are immunogens and virus-like particles (VLPs) comprising the multivalent composition. Methods of generating an immune response in a human or non-human subject by administering the multivalent composition are provided. In particular, the multivalent immunogen comprises isolated, broadly reactive hemagglutinin (HA) protein antigens of influenza virus strains, such as H1, H3, and IBV, and / or viral neuraminidase (NA) N1 and N2 protein antigens, which may be recombinant and / or recombinantly produced.

Description

[0001]Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 PENTAVALENT AND OCTAVALENT INFLUENZA VIRUS IMMUNOGENS, COMPOSITIONS AND METHODS OF USE THEREOF CROSS REFERENCE TO RELATED APPLICATIONS This application claims priority to and benefit of U.S. Provisional Application No. 63 / 556,907, filed on February 23, 2024, U.S. Provisional Application No.63 / 556,916, filed on February 23, 2024, and Indian Patent Application No.202411013142, filed on February 23, 2024, the entire contents of each of which are incorporated by reference herein. SEQUENCE LISTING This application contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. The Sequence Listing XML file, created on February 19, 2025, is named 173093-011902PCT_SL.xml and is 117,551 bytes in size. BACKGROUND Influenza viruses cause serious respiratory disease and associated afflictions in millions of people, resulting in severe morbidity and mortality each year, both in the United States and worldwide. The effectiveness of current influenza virus vaccines vary from year to year ranging from 10% to 60%. Current vaccines typically contain three to four seasonal virus strains or subtypes, which need to be updated annually. Accurate predictions of circulating virus strains are difficult due to antigenic variations of the virus from constant mutations and immune selective pressures. Because a severe flu season can kill approximately 50,000 people in the United States alone, new and improved immunogens and vaccines that provide broad and long lasting protection against both circulating human and zoonotic virus strains, particularly, influenza virus strains in present and future circulation, are urgently needed. SUMMARY OF THE DISCLOSURE Featured and described herein are multivalent (i.e., pentavalent or octavalent) influenza virus immunogens and compositions that are composed of five (pentavalent) or eight (octavalent), isolated, discrete influenza virus hemagglutinin (HA) and / or neuraminidase (NA) antigen polypeptide sequences, or the polynucleotide sequences encoding these virus antigen polypeptides. The isolated influenza virus antigen polypeptides or virus antigen polypeptide Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 sequences are also called “virus antigens” or “virus antigen sequences,” respectively, herein. Compositions or formulations that contain the five or eight influenza virus HA and / or NA antigens or encoding polynucleotide sequences are described. Such compositions and formulations are referred to as pentavalent / octavalent (i.e., pentavalent or octavalent) immunogen or vaccine compositions or formulations. In embodiments, the pentavalent / octavalent immunogen, composition, or a formulation thereof, is a pharmaceutically acceptable product that contains other physiologically or pharmaceutically acceptable components, agents, or ingredients. The influenza virus HA and NA antigens or antigen sequences contained in the pentavalent / octavalent immunogen or vaccine as described may be derived from the same or different influenza virus types, subtypes, and / or strains. As described herein, a pentavalent / octavalent immunogen comprising isolated, non-naturally occurring, broadly reactive HA and NA antigens and antigen sequences derived from influenza viruses, such as influenza H1, H2, H3, H5, H7, and / or IBV (influenza B virus) HA antigens, and / or N1 and N2 NA antigens, (also referred to as “H1, H2, H3, H5, H7, IBV, N1, and N2 influenza,” “H1, H2, H3, H5, H7, IBV, N1 and N2 influenza viruses,” or simply, “H1, H2, H3, H5, H7, IBV, N1 and N2” herein, are provided. In embodiments, the HA and NA antigens contained in the pentavalent / octavalent immunogen, composition, or vaccine are recombinant proteins and / or are recombinantly produced. The influenza virus antigens included in the pentavalent / octavalent immunogen or vaccine as described herein reflect structural proteins or peptides and include, for example, influenza virus hemagglutinin (HA) protein antigens and / or neuraminidase (NA) protein antigens. In embodiments, the immunogen may include the HA1 (head) or HA2 (tail or stalk) portions of the HA protein. The pentavalent / octavalent influenza antigen composition and formulation is a potent immunogen that elicits a broadly reactive immune response against the HA and / or NA influenza virus proteins and, ultimately, against present and future virus strains in a subject. As referred to herein, the virus antigens or antigen sequences (e.g., influenza virus antigens) that elicit an immune response in a subject are immunogenic antigens (i.e., immunogens). The terms “immunogen” and “vaccine” are used interchangeably herein. The pentavalent / octavalent influenza virus immunogen is termed broadly reactive, because it can elicit the production of broadly reactive antibodies that are directed against different subtypes or strains of influenza viruses having both sequence similarity and variability, and epitope (antigenic determinant) diversity in their protein antigens and sequences thereof, in particular, the HA antigen and / or the neuraminidase (NA) antigen of influenza virus. Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 The multivalent nature of the pentavalent / octavalent virus antigen immunogens described herein may offer improved and / or superior protection against disease and pathologies associated with infection by influenza viruses. Without wishing to be bound by theory, the presence of more than one immunogenic antigen protein or nucleic acid sequence in the pentavalent / octavalent immunogen or vaccine preparation or composition elicits a more robust immune response in a subject to whom the pentavalent / octavalent immunogen is administered and more robust immune protection and treatment against disease caused by influenza viruses of differing types and subtypes following infection. In addition, the immune response may be more long-lasting in the subject, for example, for at least 3, 4, 5, 6, 7, 8, 9, or 10 months, or longer. There are four different types of influenza viruses, three of which (influenza A, B, and C) infect people. Of those three infectious viruses, the influenza A and B subsets are the most common types, and each of these subsets develops different strains or subtypes. Influenza A and B viruses routinely spread in humans and cause seasonal flu epidemics. By way of nonlimiting example, the H1N1, H2N2, H3N2, and H5N1 strains are subtypes of influenza A that typically cause severe flu disease and that adapt to evade being eradicated by constantly changing their surface proteins, such as the hemagglutinin (HA) protein. Strains of influenza virus have been particularly problematic to treat because of unusually high rate of mutation and an inability to generate vaccines that were effective against the relatively rapid changes that occurred in the HA surface protein. In an embodiment, at least one of the immunogenic virus antigens (or antigen sequence), or encoding polynucleotide, in the pentavalent / octavalent immunogen is derived from an influenza A virus. In certain embodiments, the immunogenic virus antigens (antigen sequences), or encoding polynucleotides, in the multimeric immunogen are derived from an H1 or H3 influenza virus strain, type, or subtype. In an embodiment, at least one of the immunogenic virus antigens (or antigen sequence), or encoding polynucleotide, in the pentavalent / octavalent immunogen is derived from an influenza B virus (IBV). In an embodiment, the virus antigen is a structural protein of the virus. In a particular embodiment, the influenza virus antigens in the pentavalent / octavalent composition / vaccine described herein include hemagglutinin (HA) and neuraminidase (NA) antigens, which are immunogenic. In an aspect, the isolated, non-naturally occurring influenza virus HA and NA antigen proteins (e.g., structural antigens) and their amino acid sequences as described herein contain broadly reactive epitopes that reflect sequence similarities and variabilities of past, present and future influenza virus antigens. Such antigen sequences and the antigens comprising the sequences are thus “non-naturally occurring, broadly reactive” antigens. The antigens are Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 immunogenic and, when introduced into or administered to a subject, elicit an immune response in which broadly reactive antibodies, such as neutralizing antibodies, are produced and directed against HA and NA influenza virus antigens, in particular, H1, H2, H3, H5, H7, IBV, N1 and / or N2 influenza virus protein antigens, in the subject. In an embodiment, the elicited antibodies are also reactive against related, yet nonidentical H1, H2, H3, H5, H7, IBV, N1 and / or N2 influenza virus types, respectively. In an embodiment, such influenza virus antigen sequences are amino acid sequences. In an embodiment, the influenza virus antigen sequences are polynucleotide sequences, for example, polynucleotide sequences that encode the amino acid sequences of the antigens described herein. For ease of reference, a “non-naturally occurring, broadly reactive” antigen of an influenza virus described herein is referred to as a “broadly reactive antigen.” Accordingly, the broadly reactive influenza virus antigens described herein are immunogenic, as they elicit a broadly reactive immune response in a subject following administration. The immune response is particularly in the form of a neutralizing antibody response, for example, neutralizing antibodies that are specifically directed against the HA and / or NA antigens of influenza virus and that neutralize the activity of the HA and / or NA proteins, as well as a T-cell response. For ease of reference, a non-naturally occurring, broadly reactive, influenza virus immunogen as described herein is referred to as a “broadly reactive immunogen.” Also provided are methods of using the pentavalent HA and NA immunogen as described herein to induce an immune response against influenza infection, disease, and / or the symptoms thereof, in a subject. In a particular embodiment, the influenza virus antigen is the HA, HA1, or HA2 protein of influenza virus type or subtype, or a virus type related thereto, or an antibody binding portion thereof. Methods of using the immunogens to induce an immune response in a subject are also provided. In an aspect, a pentavalent immunogen or vaccine is provided. The pentavalent immunogen or vaccine comprises five, isolated, non-naturally occurring and immunogenic influenza virus hemagglutinin (HA) and neuraminidase (NA) antigens as follows: SEQ ID NO: 1 (Y2 (H1 HA)), SEQ ID NO: 2 (NG2 (H3 HA)), SEQ ID NO: 3 (BC2 (IBV HA)), SEQ ID NO: 4 (N1-I (N1 NA)), and SEQ ID NO: 5 (N2-B (N2 NA)), antigen binding portions thereof, or encoding polynucleotides thereof. In an embodiment of the pentavalent immunogen or vaccine, the encoding polynucleotides comprise SEQ ID NOs: 16-20, respectively. In another aspect, the disclosure features an octavalent immunogen or vaccine containing eight, isolated, non-naturally occurring and immunogenic influenza virus hemagglutinin (HA) and neuraminidase (NA) antigens, or antigen-binding portions thereof, or polynucleotides encoding the antigens or antigen-binding portions thereof. The antigens contain the following Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 amino acid sequences: a) SEQ ID NO: 51 (Y4 (H1 HA)), b) SEQ ID NO: 40 (NG3 (H3 HA)), c) SEQ ID NO: 4 (N1I (N1 NA)), d) SEQ ID NO: 65 (N2A (N2 NA)), e) SEQ ID NO: 69 (BC3 (IBV HA)) or SEQ ID NO: 3 (BC2 (IBV HA)), f) SEQ ID NO: 56 (Z1 (H2 HA)), g) SEQ ID NO: 34 (IAN8 (H5 HA)), and h) SEQ ID NO: 45 (Q6 (H7 HA)). In another aspect, the disclosure features an octavalent immunogen or vaccine containing eight, isolated, non-naturally occurring and immunogenic influenza virus hemagglutinin (HA) and neuraminidase (NA) antigens, or antigen-binding portions thereof, or polynucleotides encoding the antigens, or antigen-binding portions thereof. The antigens contain the following amino acid sequences: a) SEQ ID NO: 53 (sY4 (sH1 HA)), b) SEQ ID NO: 42 (sNG3 (sH3 HA)), c) SEQ ID NO: 62 (sN1I (sN1 NA)), d) SEQ ID NO: 67 (sN2A (sN2 NA)), e) SEQ ID NO: 71 (sBC3 (sIBV HA)) or SEQ ID NO: 8 (sBC2 (sIBV HA)), f) SEQ ID NO: 58 (sZ1 (sH2 HA)), g) SEQ ID NO: 36 (sIAN8 (sH5 HA)), and h) SEQ ID NO: 47 (sQ6 (sH7 HA)). In another aspect, the disclosure features a composition or formulation containing the octavalent immunogen or vaccine as described herein, or embodiments thereof. In another aspect, the disclosure features a pharmaceutically acceptable composition or formulation containing the octavalent immunogen or vaccine as described herein, or embodiments thereof, and a pharmaceutically acceptable excipient, diluent, or carrier. In another aspect, the disclosure features a virus-like particle (VLP) containing the octavalent immunogen or vaccine as described herein, or embodiments thereof. In another aspect, the disclosure features a composition or formulation containing a VLP as described herein, or embodiments thereof, and a pharmaceutically acceptable carrier, diluent, or excipient. In another aspect, the disclosure features an immunogenic composition or vaccine containing the octavalent immunogen or vaccine as described herein, or embodiments thereof. In another aspect, the disclosure features a method of generating or eliciting an immune response in a subject. The method involves administering to the subject an effective amount of the octavalent immunogen or vaccine, the composition or formulation, or the virus-like particle (VLP) as described herein, or embodiments thereof. In another aspect, the disclosure features a method of generating or eliciting an immune response in a subject. The method involves administering to the subject an effective amount of the pharmaceutical composition or formulation as described herein, or embodiments thereof. In another aspect, the disclosure features a method of treating, ameliorating, or abrogating disease and / or symptoms thereof associated with influenza virus infection in a Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 subject. The method involves administering to the subject an effective amount of the pharmaceutical composition or formulation as described herein, or embodiments thereof. In another aspect, the disclosure features an octavalent immunogen or vaccine containing eight, isolated, non-naturally occurring and immunogenic influenza virus hemagglutinin (HA) and neuraminidase (NA) antigens, or antigen-binding portions thereof, or polynucleotides encoding the antigens or antigen-binding portions thereof. The antigens contain the following amino acid sequences: i) a) SEQ ID NO: 51 (Y4 (H1 HA)), b) SEQ ID NO: 40 (NG3 (H3 HA)), c) SEQ ID NO: 4 (N1I (N1 NA)), d) SEQ ID NO: 65 (N2A (N2 NA)), e) SEQ ID NO: 69 (BC3 (IBV HA)) or SEQ ID NO: 3 (BC2 (IBV HA)), f) SEQ ID NO: 56 (Z1 (H2 HA)), g) SEQ ID NO: 34 (IAN8 (H5 HA)), and h) SEQ ID NO: 45 (Q6 (H7 HA)); or ii) a) SEQ ID NO: 53 (sY4 (sH1 HA)), b) SEQ ID NO: 42 (sNG3 (sH3 HA)), c) SEQ ID NO: 62 (sN1I (sN1 NA)), d) SEQ ID NO: 67 (sN2A (sN2 NA)), e) SEQ ID NO: 71 (sBC3 (sIBV HA)) or SEQ ID NO: 8 (sBC2 (sIBV HA)), f) SEQ ID NO: 58 (sZ1 (sH2 HA)), g) SEQ ID NO: 36 (sIAN8 (sH5 HA)), and h) SEQ ID NO: 47 (sQ6 (sH7 HA)). The immunogen or vaccine is formulated for intranasal administration or administered intranasally together with a c-di-AMP cyclic dinucleotide adjuvant. In another aspect, the disclosure features a method of treating, ameliorating, or abrogating disease and / or symptoms thereof associated with influenza virus infection in a subject. The method involves intranasally administering to the subject an effective amount of the octavalent immunogen or vaccine as described herein, or embodiments thereof, and the c-di- AMP adjuvant. In an aspect, a pharmaceutically acceptable composition or formulation comprising the above-delineated pentavalent immunogen or vaccine comprising HA and NA antigens comprising SEQ ID NO: 1 (Y2 (H1 HA)), SEQ ID NO: 2 (NG2 (H3 HA)), SEQ ID NO: 3 (BC2 (IBV HA)), SEQ ID NO: 4 (N1-I (N1 NA)), and SEQ ID NO: 5 (N2-B (N2 NA)), antigen binding portions thereof, or encoding polynucleotides thereof, and a pharmaceutically acceptable excipient, diluent, or carrier is provided. In an aspect, a pentavalent immunogen or vaccine comprising five, isolated, non- naturally occurring and immunogenic influenza virus hemagglutinin (HA) and neuraminidase (NA) antigens, in soluble form, comprising SEQ ID NO: 6 (sY2 (H1 HA)), SEQ ID NO: 7 (sNG2 (H3 HA)), SEQ ID NO: 8 (sBC2 (IBV HA)), SEQ ID NO: 9 (sN1-I (N1 NA)), and SEQ ID NO: 10 (sN2-B (N2 NA)), antigen binding portions thereof, or encoding polynucleotides thereof, is provided. In an embodiment of the pentavalent immunogen or vaccine, the encoding polynucleotides comprise SEQ ID NOs: 11-15, respectively. Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 In an aspect, a pharmaceutically acceptable composition or formulation comprising the above-delineated pentavalent immunogen or vaccine comprising HA and NA antigens comprising SEQ ID NO: 6 (sY2 (H1 HA)), SEQ ID NO: 7 (sNG2 (H3 HA)), SEQ ID NO: 8 (sBC2 (IBV HA)), SEQ ID NO: 9 (sN1-I (N1 NA)), and SEQ ID NO: 10 (sN2-B (N2 NA)), antigen binding portions thereof, or encoding polynucleotides thereof, and a pharmaceutically acceptable excipient, diluent, or carrier is provided. In an embodiment of the pentavalent / octavalent immunogen or vaccine of any of the above-delineated aspects and / or embodiments thereof, the encoding polynucleotides comprise DNA, RNA, or mRNA. In an embodiment of the pentavalent / octavalent immunogen or vaccine of any above-delineated aspects and / or embodiments thereof, the HA and NA antigens are recombinant and / or are recombinantly produced. In an aspect, a composition or formulation comprising the pentavalent immunogen or vaccine as delineated above and / or embodiments thereof is provided. In an embodiment, the composition or formulation further comprises a pharmaceutically acceptable excipient, diluent, or carrier. In an embodiment of the above-delineated composition or formulation and / or embodiments thereof, the composition or formulation further comprises an adjuvant. In an embodiment, the adjuvant is a dinucleotide adjuvant. In an embodiment, the dinucleotide adjuvant is cyclic-di-AMP (c-di-AMP). In another aspect, a virus-like particle (VLP) comprising the pentavalent immunogen or vaccine of any of the above-delineated aspects and / or embodiments thereof is provided. In an embodiment, the VLP comprises a pharmaceutically acceptable carrier, diluent, or excipient. In an embodiment, the VLP further comprises an adjuvant. In an embodiment, the adjuvant is cyclic-di-AMP (c-di-AMP). In embodiments, the pentavalent / octavalent immunogen or vaccine of any of the above-delineated aspects and / or embodiments thereof, the composition or formulation of any of the above-delineated aspects and / or embodiments thereof, or the virus-like particle (VLP) of any of the above-delineated aspects and / or embodiments thereof, generates an immune response in a subject following immunization. In an embodiment, the immune response comprises the production of neutralizing antibodies. In an embodiment, the immune response comprises the production of antibodies having hemagglutinin inhibitory activity and / or neuraminidase inhibitory activity. In an embodiment, the immune response comprises the production of T-lymphocytes. In an aspect, an immunogenic composition or vaccine comprising the pentavalent immunogen or vaccine of any of the above-delineated aspects and / or embodiments thereof, is Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 provided. In an embodiment, the immunogenic composition or vaccine includes a pharmaceutically acceptable carrier, diluent, or excipient. In an embodiment, the immunogenic composition or vaccine, which may include a pharmaceutically acceptable carrier, diluent, or excipient, further comprises an adjuvant. In an embodiment, the adjuvant is a cyclic dinucleotide. In an embodiment, the cyclic dinucleotide adjuvant is cyclic-di-AMP (c-di-AMP). In another aspect, a method of generating or eliciting an immune response in a subject is provided, in which the method involves administering to a subject in need thereof an effective amount of the pentavalent immunogen or vaccine, the composition or formulation, or the virus- like particle (VLP) of any of the above-delineated aspects and / or embodiments thereof. In another aspect, a method of generating or eliciting an immune response in a subject is provided, in which the method involves administering to a subject in need thereof an effective amount of an immunogenic composition or vaccine comprising the pentavalent immunogen, or a pharmaceutical composition or formulation of any of the above-delineated aspects and / or embodiments thereof. In another aspect, a method of treating, ameliorating, or abrogating disease and / or symptoms thereof associated with influenza virus infection in a subject is provided, in which the method involves administering to a subject in need thereof an effective amount of a immunogenic composition or vaccine comprising the pentavalent immunogen, or a pharmaceutical composition or formulation of any of the above-delineated aspects and / or embodiments thereof. In an embodiment, the influenza virus comprises influenza subtype A virus and / or influenza subtype B virus. In an embodiment, the subject generates an immune response directed against the antigens in the pentavalent / octavalent composition / vaccine, in which the immune response may include the production of antibodies, such as HA and / or NA neutralizing antibodies and the elicitation of a cellular immune response, such as a T cell response. In an embodiment of any of the above-delineated methods and / or embodiments thereof, the immune response is generated or elicited against hemagglutinin (HA) and neuraminidase (NA) antigens of influenza virus subtypes. In an embodiment, the influenza virus subtypes comprise H1, H3 IBV, N1 and N2. In an embodiment of the above-delineated methods and / or embodiments thereof, the pentavalent / octavalent immunogen or vaccine, the composition or formulation, the virus-like particle (VLP), or the pharmaceutical composition or formulation is delivered intranasally. In an embodiment of any of the above-delineated methods and / or embodiments thereof, the method further involves generating an immune response in the subject which comprises the production of neutralizing antibodies. In an embodiment of the methods, Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 the immune response comprises generating a cellular immune response comprising the production of T-lymphocytes. In embodiments of any of the above-delineated methods and / or embodiments thereof, an adjuvant is admixed with the pentavalent / octavalent immunogen or vaccine, the composition or formulation, the virus-like particle (VLP), or the pharmaceutical composition or formulation, or is concomitantly administered to the subject. In an embodiment, the adjuvant is a cyclic dinucleotide. In an embodiment, the adjuvant is c-di-AMP. In an embodiment of the composition or formulation, the VLP, the immunogenic composition or vaccine, or the method in which an adjuvant and / or a cyclic dinucleotide adjuvant is included or administered, the adjuvant comprises a cyclic di-nucleotide (CDN), such as c-di-AMP adjuvant, according to the following formula or structure: , wherein A, A’ is independently from one another S or O; X is independently from one another S, N, O, CH2; Y, Y’ is independently from one another NH, CH2, O; Z, Z’ is independently from one another NH, CH2, O; R1 is independently from one another hydrogen or O or absent; R2 is independently from one another NH2, O, H, or a hydrogen; R3is independently from one another absent if a covalent bond is present between the Z or Z’ and the C atom, or is hydrogen, OH, halogen, a straight or branched C1-C6 alkyl group, or a straight or branched C1-C6 alkoxy group which may optionally be substituted; R4is independently from one another hydrogen, halogen, or a straight or branched C1-C6alkyl group, which may optionally be substituted; and ... is a single or double bond; or conjugates thereof, and salts or solvates thereof. In an embodiment, the CDN adjuvant has a purine residue selected from adenine, xanthine or hypoxanthine, or combinations thereof. In an embodiment, Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 both purine residues in the CDN adjuvant comprise adenine. In an embodiment, the CDN adjuvant is characterized in that R3 is a OH group, X is an oxygen atom and Y, Y’, Z and Z’ are oxygen. In an embodiment, the CDN is a compound selected from the group of cyclic bis (3’-5’) diadenylic acid (CDA) or c-di-AMP, c-di-IMP, c-IAMP, or a cyclic di-AMP thiophosphate, c-di- MP thiophosphate and c-IAMP thiophosphate. In an embodiment of any of the above-delineated methods and / or embodiments thereof, the immune response is prophylactic or therapeutic. In an embodiment of any of the above- delineated methods and / or embodiments thereof, the subject is a human subject, a non-human subject, or a veterinary subject. In an embodiment of any of the above-delineated methods and / or embodiments thereof, the method (i) treats or prevents the onset or progression of disease associated with or caused by influenza virus infection; (ii) reduces horizontal transfer of influenza virus from an infected subject to a susceptible host; (iii) generates a rapid immune response following a weekly, biweekly or monthly administration schedule; and / or (iv) comprises administration using a prime-boost or prime-pull scheme of immunization or vaccination. In an embodiment of any of the above-delineated methods and / or embodiments thereof, the pentavalent / octavalent immunogen or vaccine, the composition or formulation, the virus-like particle (VLP), or the pharmaceutical composition or formulation is administered in a dose range of, e.g., 0.001 mg / mL to 10 mg / mL, in combination with or associated with administration of c-di-AMP in a concentration range from 0.01 to 10 mg / mL (or 5 μg to 500 μg, or 10 μg to 300 μg, or 10 μg to 150 μg, or 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 μg). In embodiments, the pentavalent / octavalent immunogen or vaccine, the composition or formulation, the virus-like particle (VLP), or the pharmaceutical composition or formulation is formulated as a soluble formulation in an excipient or buffer comprising muco- adhesives, stabilizers and preservatives. In an aspect, the pentavalent immunogen or vaccine of any of the above-delineated methods and / or embodiments thereof is provided, wherein the immunogen or vaccine is formulated in combination with aluminum hydroxide or a phosphate adjuvant, in combination with c-di-AMP, in an excipient of buffered saline solution and, optionally, muco-adhesives, stabilizers and preservatives. In an aspect, a pentavalent immunogen or vaccine comprising five, isolated, non- naturally occurring and immunogenic influenza virus hemagglutinin (HA) and neuraminidase (NA) antigen proteins is provided, as follows: (i) SEQ ID NO: 1 (Y2 (H1 HA)), SEQ ID NO: 2 (NG2 (H3 HA)), SEQ ID NO: 3 (BC2 (IBV HA)), SEQ ID NO: 4 (N1-I (N1 NA)), and SEQ ID NO: 5 (N2-B (N2 NA)), binding portions thereof, or encoding polynucleotides thereof; or (ii) Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 SEQ ID NO: 6 (sY2 (H1 HA)), SEQ ID NO: 7 (sNG2 (H3 HA)), SEQ ID NO: 8 (sBC2 (IBV HA)), SEQ ID NO: 9 (sN1-I (N1 NA)), and SEQ ID NO: 10 (sN2-B (N2 NA)), binding portions thereof, or encoding polynucleotides thereof, formulated or administered with a c-di-AMP cyclic dinucleotide adjuvant for intranasal administration. In an embodiment, the encoding polynucleotides comprise DNA, RNA, or mRNA. In another aspect, a method of treating, ameliorating, or abrogating disease and / or symptoms thereof associated with influenza virus infection in a subject is provided, in which the method involves intranasally administering to a subject in need thereof an effective amount of the pentavalent immunogen or vaccine described directly above, in which the method includes administering a c-di-AMP adjuvant. In an embodiment, the method generates a prophylactic or therapeutic immune response in the subject. In an embodiment, the subject is a human subject, a non-human subject, or a veterinary subject. In an embodiment, the method (i) treats or prevents the onset or progression of disease associated with or caused by influenza virus infection; (ii) reduces horizontal transfer of influenza virus from an infected subject to a susceptible host; (iii) generates a rapid immune response following a weekly, biweekly or monthly administration schedule; and / or (iv) comprises administration using a prime-boost or prime-pull regimen of immunization or vaccination. In an embodiment, the HA and NA antigen proteins of a pentavalent / octavalent immunogen or vaccine of any of the above-delineated aspects and / or embodiments thereof are recombinant and / or are recombinantly produced. In another aspect, a pentavalent composition is provided, in which the composition includes five, isolated, non-naturally occurring and immunogenic influenza virus hemagglutinin (HA) and neuraminidase (NA) antigen proteins as follows: (i) SEQ ID NO: 1 (Y2 (H1 HA)), SEQ ID NO: 2 (NG2 (H3 HA)), SEQ ID NO: 3 (BC2 (IBV HA)), SEQ ID NO: 4 (N1-I (N1 NA)), and SEQ ID NO: 5 (N2-B (N2 NA)), antigen binding portions thereof, or encoding polynucleotides thereof; or (ii) SEQ ID NO: 6 (sY2 (H1 HA)), SEQ ID NO: 7 (sNG2 (H3 HA)), SEQ ID NO: 8 (sBC2 (IBV HA)), SEQ ID NO: 9 (sN1-I (N1 NA)), and SEQ ID NO: 10 (sN2-B (N2 NA)), antigen binding portions thereof, or encoding polynucleotides thereof, wherein the composition is formulated or associated with a cyclic dinucleotide adjuvant capable of enhancing an anti-viral immune response. In an embodiment, the HA and NA antigen proteins are recombinant and / or are recombinantly produced. In an embodiment, the cyclic dinucleotide adjuvant is as described herein. In an embodiment, the cyclic dinucleotide is c-di- AMP. Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 In another aspect, a method of producing a pentavalent composition comprising five, isolated, non-naturally occurring and immunogenic influenza virus hemagglutinin (HA) and neuraminidase (NA) antigen proteins as follows: (i) SEQ ID NO: 1 (Y2 (H1 HA)), SEQ ID NO: 2 (NG2 (H3 HA)), SEQ ID NO: 3 (BC2 (IBV HA)), SEQ ID NO: 4 (N1-I (N1 NA)), and SEQ ID NO: 5 (N2-B (N2 NA)) or encoding polynucleotides thereof; or (ii) SEQ ID NO: 6 (sY2 (H1 HA)), SEQ ID NO: 7 (sNG2 (H3 HA)), SEQ ID NO: 8 (sBC2 (IBV HA)), SEQ ID NO: 9 (sN1-I (N1 NA)), and SEQ ID NO: 10 (sN2-B (N2 NA)) or encoding polynucleotides thereof, is provided, in which the method involves contacting a cell with one or more polynucleotides encoding the HA and NA antigens under conditions sufficient for expression in the cell; expressing the protein antigens in the cell; and isolating and / or purifying the expressed protein antigens. In an embodiment, the cell is a prokaryotic cell. In an embodiment, the cell is a eukaryotic cell. In an embodiment, the cell is contacted with one or more expression vectors containing the encoding polynucleotides for expression of the protein antigens in the cell. In an embodiment, the expression vector is a eukaryotic expression vector. In an embodiment, the expression vector is transduced or transfected into the cell. In yet another aspect, a method of detecting reactivity of antibodies against a pentavalent composition is provided, in which the pentavalent composition comprises five, isolated, non- naturally occurring and immunogenic influenza virus hemagglutinin (HA) and neuraminidase (NA) antigen proteins as follows: (i) SEQ ID NO: 1 (Y2 (H1 HA)), SEQ ID NO: 2 (NG2 (H3 HA)), SEQ ID NO: 3 (BC2 (IBV HA)), SEQ ID NO: 4 (N1-I (N1 NA)), and SEQ ID NO: 5 (N2- B (N2 NA)) or antibody binding portions thereof; or (ii) SEQ ID NO: 6 (sY2 (H1 HA)), SEQ ID NO: 7 (sNG2 (H3 HA)), SEQ ID NO: 8 (sBC2 (IBV HA)), SEQ ID NO: 9 (sN1-I (N1 NA)), and SEQ ID NO: 10 (sN2-B (N2 NA)) or antibody binding portions thereof, in which method involves contacting the antigen proteins, or the binding portions thereof, of the composition with an isolated or obtained sera or sample to be tested under conditions sufficient for binding of antibodies in the sera or the sample to the antigen proteins; and detecting the binding of antibodies in the sera or sample to the antigen proteins, thereby detecting reactivity of antibodies against the pentavalent composition. In an embodiment, the antigen proteins are detectably labeled or wherein a detectably labeled secondary antibody that reacts with antibodies in the sera or sample is included in the method. In an embodiment, the antigen proteins are linked, coupled, or affixed to a solid support. In an embodiment, the detected antibodies neutralize activity of influenza virus hemagglutinin and / or neuraminidase antigens. In an aspect, the polynucleotides encoding the antigens contain SEQ ID NOs: 68, 37, 43, 48, 54, 59, 63, 72, and / or 13. Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 In an aspect, one or more of the antigens further contains between 5 and 10 consecutive His amino acids. In embodiments, the one or more of the HA antigens contain the between 5 and 10 consecutive His amino acids at the C-terminus. In an aspect of the disclosure, the sN2A and / or sN1I antigens further contain a peptide having an amino acid sequence containing SEQ ID NO: 33 fused to the N-terminus of the antigen. In an aspect, one or more of the HA antigens further contain a peptide containing one of the following amino acid sequences fused to the C-terminus of the antigen: SEQ ID NO: 31, 38, 27, 49, 23, or 60. In an aspect, the composition or formulation further contains a pharmaceutically acceptable excipient, diluent, or carrier. In an aspect, the composition or formulation further contains an adjuvant. In embodiments, the adjuvant is a dinucleotide adjuvant. In embodiments, the dinucleotide adjuvant is cyclic-di-AMP (c-di-AMP). In an aspect, the composition or formulation further contains an adjuvant. In embodiments, the adjuvant is cyclic-di-AMP (c-di-AMP). In an aspect, the octavalent / pentavalent immunogen or vaccine, the composition or formulation, or the virus-like particle (VLP) generates an immune response in a subject following immunization. In embodiments, the immune response involves the production of neutralizing antibodies. In embodiments, the immune response involves the production of antibodies having hemagglutinin inhibitory activity and / or neuraminidase inhibitory activity. In embodiments, the immune response involves the production of T-lymphocytes. In an aspect, the immunogenic composition or vaccine further contains a pharmaceutically acceptable carrier, diluent, or excipient. In an aspect, the immunogenic composition or vaccine further contains an adjuvant. In an aspect, the adjuvant is cyclic-di-AMP (c-di-AMP). In an aspect, the influenza virus infection is an influenza subtype A virus infection and / or influenza subtype B virus infection. In an aspect, the immune response is generated or elicited against hemagglutinin (HA) and neuraminidase (NA) antigens of influenza virus subtypes. In embodiments, the influenza virus subtypes contain H1, H2, H3, H5, H7, and IBV. In an aspect, the octavalent / pentavalent immunogen or vaccine, the composition or formulation, the virus-like particle (VLP), or the pharmaceutical composition or formulation is delivered intranasally. Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 In an aspect, the method further involves generating an immune response in the subject that involves the production of neutralizing antibodies. In an aspect, the immune response involves generating a cellular immune response involving the production of T-lymphocytes. In an aspect, an adjuvant is admixed with the octavalent / pentavalent immunogen or vaccine, the composition or formulation, the virus-like particle (VLP), or the pharmaceutical composition or formulation of an aspect of the disclosure, or embodiments thereof, or is concomitantly administered to the subject. In embodiments, the adjuvant is a cyclic dinucleotide (CDN). In embodiments, the adjuvant is a CDN or c-di-AMP having the structure or formula set forth hereinabove in connection with the composition or formulation, VLP, immunogenic composition or vaccine, or methods as described herein. In an embodiment, the immune response is prophylactic or therapeutic. In another embodiment, the subject is a human subject, a non-human subject, or a veterinary subject. In an aspect, the described method: (i) treats or prevents the onset or progression of disease associated with or caused by influenza virus infection; (ii) reduces horizontal transfer of influenza virus from an infected subject to a susceptible host; (iii) generates a rapid immune response following a weekly, biweekly or monthly administration schedule; and / or (iv) involves administration using a prime-boost or prime-pull scheme of immunization or vaccination. In an aspect, the octavalent / pentavalent immunogen or vaccine, the composition or formulation, the virus-like particle (VLP), or the pharmaceutical composition or formulation is administered at a total antigen concentration of from 0.001 mg / mL to 10 mg / mL in combination with c-di-AMP at a concentration of from 0.01 to 10 mg / mL. In an aspect, the octavalent / pentavalent immunogen or vaccine, the composition or formulation, the virus-like particle (VLP), or the pharmaceutical composition or formulation is administered as a soluble formulation in an excipient or buffer. In an aspect, the soluble formulation further contains a muco-adhesive, stabilizer, and / or preservative. In an aspect, the octavalent / pentavalent immunogen or vaccine is formulated in combination with one or more adjuvants. In embodiments, the one or more adjuvants are selected from one or more of aluminum hydroxide, phosphate adjuvants, and c-di-AMP. In an aspect, the octavalent / pentavalent immunogen or vaccine is formulated in combination with an excipient and / or a buffered saline solution. In an aspect, the octavalent / pentavalent immunogen or vaccine is formulated in combination with a muco-adhesive, stabilizer, and / or preservative. In an aspect of the disclosure, or embodiments thereof, the polynucleotides encoding the HA or NA antigens contain SEQ ID NO: 66, 35, 41, 46, 52, 57, 19, 70, and / or 18. In embodiments, the polynucleotides contain DNA, RNA, or mRNA. Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 In an aspect of the disclosure, or embodiments thereof, the octavalent / pentavalent immunogen or vaccine as described contains immunogenic influenza virus hemagglutinin (HA) and neuraminidase (NA) antigens at a cumulative concentration of between about 0.001 and 10 mg / mL and c-di-AMP at a concentration between about 0.01 and 10 mg / mL or between about 0.020 mg / mL and 0.300 mg / mL. In an aspect of the disclosure, or embodiments thereof, the octavalent / pentavalent immunogen or vaccine is a soluble formulation containing an excipient based in a buffer. In some embodiments, the buffer is phosphate buffered saline. In an aspect of the disclosure, or embodiments thereof, the octavalent / pentavalent immunogen or vaccine contains commercial muco-adhesives, stabilizers, and / or preservatives. In an aspect of the disclosure, or embodiments thereof, the octavalent / pentavalent immunogen or vaccine contains an aluminum hydroxide or phosphate adjuvant. In an aspect of the disclosure, or embodiments thereof, the octavalent / pentavalent immunogen or vaccine is administered alone or as part of a formulation with alum or other depot adjuvants. In an aspect of the disclosure, or embodiments thereof, the octavalent / pentavalent immunogen or vaccine is formulated together with one or more adjuvants or is administered together with or mixed with the one or more adjuvants within about 30 sec, 1 min, 5 min, 10 min, 12 hours, or 1 day of administration to a subject. In an aspect of the disclosure, or embodiments thereof, the octavalent / pentavalent immunogen or vaccine is administered to a subject about every week, every 15 days, every month, or every year for a total of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, or more administrations. In an aspect, a pentavalent or octavalent immunogen or vaccine is provided, wherein the pentavalent immunogen or vaccine includes five, isolated, non-naturally occurring and immunogenic influenza virus hemagglutinin (HA) and neuraminidase (NA) antigens, or antigen binding portions thereof, or polynucleotides encoding the antigens or antigen-binding portions thereof, wherein the antigens comprise the following amino acid sequences: SEQ ID NO: 1 (Y2 (H1 HA)), SEQ ID NO: 2 (NG2 (H3 HA)), SEQ ID NO: 3 (BC2 (IBV HA)), SEQ ID NO: 4 (N1-I (N1 NA)), and SEQ ID NO: 5 (N2-B (N2 NA)); and wherein the octavalent immunogen or vaccine includes eight, isolated, non-naturally occurring and immunogenic influenza virus hemagglutinin (HA) and neuraminidase (NA) antigens, or antigen-binding portions thereof, or polynucleotides encoding the antigens or antigen-binding portions thereof, wherein the antigens comprise the following amino acid sequences: a) SEQ ID NO: 51 (Y4 (H1 HA)), b) SEQ ID NO: 40 (NG3 (H3 HA)), c) SEQ ID NO: 4 (N1I (N1 NA)), d) SEQ ID NO: 65 (N2A (N2 NA)), e) SEQ ID NO: 69 (BC3 (IBV HA)) or SEQ ID NO: 3 (BC2 (IBV HA)), f) SEQ ID NO: 56 (Z1 (H2 HA)), g) SEQ ID NO: 34 (IAN8 (H5 HA)), and h) SEQ ID NO: 45 (Q6 (H7 HA)). In an Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 embodiment, of the above-described pentavalent or octavalent immunogen or vaccine, the polynucleotides encoding the HA or NA antigens of the pentavalent immunogen or vaccine include SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, and SEQ ID NO: 20; and wherein the polynucleotides encoding the HA or NA antigens of the octavalent immunogen or vaccine include SEQ ID NO: 66, SEQ ID NO: 35, SEQ ID NO: 41, SEQ ID NO: 46, SEQ ID NO: 52, SEQ ID NO: 57, SEQ ID NO: 19, SEQ ID NO: 70, and / or SEQ ID NO: 18, optionally, wherein the polynucleotides comprise DNA, RNA, or mRNA. In another aspect, a pentavalent or octavalent immunogen or vaccine is provided, wherein the pentavalent immunogen or vaccine includes five, isolated, non-naturally occurring and immunogenic influenza virus hemagglutinin (HA) and neuraminidase (NA) antigens, which are soluble antigens, or antigen-binding portions thereof, or polynucleotides encoding the antigens or antigen-binding portions thereof, wherein the antigens include the following amino acid sequences: a) SEQ ID NO: 6 (sY2 (H1 HA)), b) SEQ ID NO: 7 (sNG2 (H3 HA)), c) SEQ ID NO: 8 (sBC2 (IBV HA)), d) SEQ ID NO: 9 (sN1-I (N1 NA)), and e) SEQ ID NO: 10 (sN2-B (N2 NA)); and wherein the octavalent immunogen or vaccine includes eight, isolated, non- naturally occurring and immunogenic influenza virus hemagglutinin (HA) and neuraminidase (NA) antigens, which are soluble antigens, or antigen-binding portions thereof, or polynucleotides encoding the antigens or antigen-binding portions thereof, wherein the antigens include the following amino acid sequences: a) SEQ ID NO: 53 (sY4 (H1 HA)), b) SEQ ID NO: 42 (sNG3 (H3 HA)), c) SEQ ID NO: 62 (sN1I (N1 NA)), d) SEQ ID NO: 67 (sN2A (N2 NA)), e) SEQ ID NO: 71 (sBC3 (IBV HA)) or SEQ ID NO: 8 (BC2 (sIBV HA)), f) SEQ ID NO: 58 (sZ1 (H2 HA)), g) SEQ ID NO: 36 (sIAN8 (H5 HA)), and h) SEQ ID NO: 47 (sQ6 (H7 HA)). In an embodiment, the polynucleotides encoding the pentavalent immunogen or vaccine comprise SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, and SEQ ID NO: 15, respectively, and the polynucleotides encoding the octavalent immunogen or vaccine comprise SEQ ID NOs: 68, 37, 43, 48, 54, 59, 63, 72, and / or 13; optionally, wherein the polynucleotides comprise DNA, RNA, or mRNA. In embodiments of the pentavalent or octavalent immunogen or vaccine as described in the above-delineated aspects and / or embodiments thereof, (i) one or more of the antigens further comprises between 5 and 10 consecutive His amino acids, and / or (ii) one or more of the HA antigens comprises the between 5 and 10 consecutive His amino acids at the C-terminus; or (iii) one or more of the soluble antigens further comprises a peptide having an amino acid sequence comprising MPMGSLQPLATLYLLGMLVASVLSAHHHHHHGSGSLVPRGSPSRSIINETADDIVYRLTVIIDD Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 RYESLKNLITLRADRLEMIINDNVSTILASIGSGTG (SEQ ID NO: 33) fused to the N-terminus of the antigen; or (iv) one or more of the HA antigens further comprises a peptide comprising one of the following amino acid sequences fused to the C-terminus of the antigen: GTGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGLNDIFEAQKIEWHEGHHHHHH (SEQ ID NO: 23); GSGYIPEAPRDGQAYVRKDGEWVLLSTFLGLNDIFEAQKIEWHEGHHHHHHGS (SEQ ID NO: 27); IGSGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGLNDIFEAQKIEWHEGHHHHHH (SEQ ID NO: 5); or GYIPEAPRDGQAYVRKDGEWVLLSTFLGSGLNDIFEAQKIEWHEGHHHHHH (SEQ ID NO: 17). In another aspect, a composition or formulation including the pentavalent or octavalent immunogen or vaccine of any of the above-delineated aspects and / or embodiments thereof is provided, which includes, or optionally includes, a pharmaceutically acceptable excipient, diluent, or carrier. In another aspect, a virus-like particle (VLP) comprising the pentavalent or octavalent immunogen or vaccine, or as delineated in any of the above aspects and / or embodiments thereof, or a composition comprising the VLP, is provided, which includes, or optionally includes a pharmaceutically acceptable carrier, diluent, or excipient. In an embodiment, the above-described composition or formulation or the virus-like particle (VLP) or composition thereof further includes an adjuvant. In another aspect, a method of generating or eliciting an immune response in a subject, or of treating, ameliorating, or abrogating disease and / or symptoms thereof associated with influenza virus infection in a subject, is provided, in which the method involves administering to the subject an effective amount of the pentavalent or octavalent immunogen or vaccine, the composition or formulation, the virus-like particle (VLP) or composition thereof as described in any of the above-delineated aspects and / or embodiments thereof. In embodiments of the method, the influenza virus comprises influenza subtype A virus and / or influenza subtype B virus; the immune response is generated or elicited against hemagglutinin (HA) and neuraminidase (NA) antigens of influenza virus subtypes; and / or the immune response is generated or elicited against hemagglutinin (HA) and neuraminidase (NA) antigens of influenza virus subtypes, which comprise H1, H2, H3, H5, H7, and IBV. In an aspect, the pentavalent or octavalent immunogen or vaccine, the composition or formulation, the virus-like particle (VLP) or composition thereof, the pharmaceutical composition or formulation, as described in any one of the above-delineated aspects and / or Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 embodiments thereof, or as used in the above-described methods, is formulated for nasal administration and / or is delivered intranasally, and / or wherein an adjuvant is admixed with the pentavalent or octavalent immunogen or vaccine, the composition or formulation, the virus-like particle (VLP), or the pharmaceutical composition or formulation, or wherein the adjuvant is concomitantly administered to the subject. In an embodiment, the adjuvant is a cyclic dinucleotide, a c-di-AMP, or comprises a c-di-AMP (CDN) adjuvant according to the formula: , wherein A, A’ is independently from one another S or O; X is independently from one another S, N, O, CH2; Y, Y’ is independently from one another NH, CH2, O; Z, Z’ is independently from one another NH, CH2, O; R1is independently from one another hydrogen or O or absent; R2 is independently from one another NH2, O, H, or a hydrogen; R3 is independently from one another absent if a covalent bond is present between the Z or Z’ and the C atom, or is hydrogen, OH, halogen, a straight or branched C1-C6alkyl group, or a straight or branched C1-C6 alkoxy group which may optionally be substituted; R4 is independently from one another hydrogen, halogen, or a straight or branched C1-C6 alkyl group, which may optionally be substituted; and “ ...” is a single or double bond; or conjugates thereof, and salts or solvates thereof; optionally, wherein the CDN has a purine residue selected from adenine, xanthine or hypoxanthine, or combinations thereof; or wherein both purine residues in the CDN comprise adenine; or wherein the CDN is characterized in that R3 is a OH group, X is an oxygen atom and Y, Y’, Z and Z’ are oxygen; and / or Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 wherein the CDN is a compound selected from the group of cyclic bis (3’-5’) diadenylic acid (CDA) or c-di-AMP, c-di-IMP, c-IAMP, or a cyclic di-AMP thiophosphate, c-di-MP thiophosphate and c-IAMP thiophosphate. In another aspect, a pentavalent or octavalent immunogen or vaccine is provided, wherein the pentavalent immunogen or vaccine includes five, isolated, non-naturally occurring and immunogenic influenza virus hemagglutinin (HA) and neuraminidase (NA) antigens or antigen- binding portions thereof, or polynucleotides encoding the antigens or antigen-binding portions thereof, wherein the antigens comprise the following amino acid sequences: (i) SEQ ID NO: 1 (Y2 (H1 HA)), SEQ ID NO: 2 (NG2 (H3 HA)), SEQ ID NO: 3 (BC2 (IBV HA)), SEQ ID NO: 4 (N1-I (N1 NA)), and SEQ ID NO: 5 (N2-B (N2 NA)), or (ii) SEQ ID NO: 6 (sY2 (H1 HA)), SEQ ID NO: 7 (sNG2 (H3 HA)), SEQ ID NO: 8 (sBC2 (IBV HA)), SEQ ID NO: 9 (sN1-I (N1 NA)), and SEQ ID NO: 10 (sN2-B (N2 NA)); or wherein the octavalent immunogen or vaccine includes eight, isolated, non-naturally occurring and immunogenic influenza virus hemagglutinin (HA) and neuraminidase (NA) antigens or antigen-binding portions thereof, or polynucleotides encoding the antigens or antigen-binding portions thereof, wherein the antigens include the following amino acid sequences: i) a) SEQ ID NO: 51 (Y4 (H1 HA)), b) SEQ ID NO: 40 (NG3 (H3 HA)), c) SEQ ID NO: 4 (N1I (N1 NA)), d) SEQ ID NO: 65 (N2A (N2 NA)), e) SEQ ID NO: 69 (BC3 (IBV HA)) or SEQ ID NO: 3 (BC2 (IBV HA)), f) SEQ ID NO: 56 (Z1 (H2 HA)), g) SEQ ID NO: 34 (IAN8 (H5 HA)), and h) SEQ ID NO: 45 (Q6 (H7 HA)); or ii) a) SEQ ID NO: 53 (Y4 (sH1 HA)), b) SEQ ID NO: 42 (NG3 (sH3 HA)), c) SEQ ID NO: 62 (N1I (sN1 NA)), d) SEQ ID NO: 67 (N2A (sN2 NA)), e) SEQ ID NO: 71 (BC3 (sIBV HA)) or SEQ ID NO: 41 (BC2 (sIBV HA)), f) SEQ ID NO: 58 (Z1 (sH2 HA)), g) SEQ ID NO: 36 (IAN8 (sH5 HA)), and h) SEQ ID NO: 47 (Q6 (sH7 HA)); Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 wherein the pentavalent or octavalent immunogen or vaccine is formulated or administered with a c-di-AMP cyclic dinucleotide adjuvant for intranasal administration; and, optionally, wherein the HA and NA antigens are recombinant and / or are recombinantly produced. In another aspect, a method of treating, ameliorating, or abrogating disease and / or symptoms thereof associated with influenza virus infection in a subject is provided, in which the method involves intranasally administering to the subject an effective amount of the pentavalent or octavalent immunogen or vaccine as described in the above aspect and the c-di-AMP adjuvant. In an embodiment, the method generates a prophylactic or therapeutic immune response in the subject. In an embodiment of the above-delineated methods and / or embodiments thereof, the subject is a human subject, a non-human subject, or a veterinary subject. In embodiments, the method (i) treats or prevents the onset or progression of disease associated with or caused by influenza virus infection; (ii) reduces horizontal transfer of influenza virus from an infected subject to a susceptible host; (iii) generates a rapid immune response following a weekly, biweekly or monthly administration schedule; and / or (iv) comprises administration using a prime-boost or prime-pull regimen of immunization or vaccination. Definitions Unless defined otherwise, all technical and scientific terms used herein have the meaning commonly understood by a person skilled in the art to which this disclosure pertains or relates. The following references provide one of skill with a general definition of many of the terms used in this disclosure: Singleton et al., Dictionary of Microbiology and Molecular Biology (2nd ed. 1994); The Cambridge Dictionary of Science and Technology (Walker ed., 1988); The Glossary of Genetics, 5th Ed., R. Rieger et al. (eds.), Springer Verlag (1991); Benjamin Lewin, Genes V, published by Oxford University Press, 1994 (ISBN 0-19-854287-9); Kendrew et al. (eds.); The Encyclopedia of Molecular Biology, published by Blackwell Science Ltd., 1994 (ISBN 0-632- 02182-9); Molecular Biology and Biotechnology: a Comprehensive Desk Reference, Robert A. Meyers (ed.), published by VCH Publishers, Inc., 1995 (ISBN 1-56081-569-8); and Hale & Marham, The Harper Collins Dictionary of Biology (1991). As used herein, the following terms have the meanings ascribed to them below, unless specified otherwise. By “adjuvant” is meant a substance or vehicle that non-specifically enhances an immune response to an antigen. Adjuvants may include a suspension of minerals (e.g., alum, aluminum hydroxide, or phosphate) on which antigen is adsorbed; or water-in-oil emulsion in which antigen solution is emulsified in mineral oil (e.g., Freund's incomplete adjuvant), sometimes with Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 the inclusion of killed mycobacteria (Freund's complete adjuvant) to further enhance antigenicity. Immunostimulatory oligonucleotides (such as those including a CpG motif) can also be used as adjuvants (see, e.g., U.S. Patent Nos.6,194,388; 6,207,646; 6,214,806; 6,218,371; 6,239,116; 6,339,068; 6,406,705; and 6,429,199). Adjuvants also include biological molecules, such as costimulatory molecules. Exemplary biological adjuvants include, without limitation, interleukin-1 (IL-2), the protein memory T-cell attractant “Regulated on Activation, Normal T Expressed and Secreted” (RANTES), granulocyte-macrophage-colony stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), granulocyte- colony stimulation factor (G-CSF), lymphocyte function-associated antigen 3 (LFA-3, also called CD58), cluster of differentiation antigen 72 (CD72), (a negative regulator of B cell responsiveness), peripheral membrane protein, B7-1 (B7-1, also called CD80), peripheral membrane protein, B7-2 (B7-2, also called CD86), the TNF ligand superfamily member 4 ligand (OX40L) or the type 2 transmembrane glycoprotein receptor belonging to the TNF superfamily (4-1BBL). In a particular embodiment, the adjuvant is a cyclic dinucleotide (CDN) that is capable of stimulating both systemic and mucosal immune responses (Ebensen, T. et al., Vaccine, 2011.29(32): p.5210-5220). In an embodiment, the cyclic dinucleotide is cyclic di- AMP (c-di-AMP). By “cyclic dinucleotide (CDN)” is meant a molecule having the following structure: , where A, A’ is independently from one another S or O; X is independently from one another S, N, O, CH2; Y, Y’ is independently from one another NH, CH2, O; Z, Z’ is independently from one another NH, CH2, O; R1 is independently from one another hydrogen or O or absent; R2 is independently from one another NH2, O, H, or a hydrogen; Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 R3 is independently from one another absent if a covalent bond is present between the Z or Z’ and the C atom, or is hydrogen, OH, halogen, a straight or branched C1-C6 alkyl group, or a straight or branched C1-C6 alkoxy group which may optionally be substituted; R4 is independently from one another hydrogen, halogen, or a straight or branched C1-C6 alkyl group, which may optionally be substituted; and “...” is a single or double bond; or conjugates thereof, and salts or solvates thereof. In some embodiments, the CDN has a purine residue from the group of adenine, xanthine or hypoxanthine residues or combinations thereof. In some embodiments, both purine residues are adenine. In some embodiments, R3 is a OH group, X is an oxygen atom and Y, Y’, Z and Z’ are oxygen. In some embodiments, the cyclic dinucleotide is selected from one or more of cyclic bis (3’-5’) diadenylic acid (CDA) or c-di-AMP, c-di-IMP, c-IAMP, or a cyclic di-AMP thiophosphate, c-di-MP thiophosphate and c-IAMP thiophosphate. In some embodiments, the CDN is c-di-AMP having the following structure: (1S,6R,8R,9R,10S,15R,17R,18R)-8,17-Bis(6-aminopurin-9-yl)-3,12-dihydroxy-3,12-dioxo- 2,4,7,11,13,16-hexaoxa-3λ5,12λ5-diphosphatricyclo[13.3.0.06,10]octadecane-9,18-diol, and CAS No.54447-84-6, or a pharmaceutically acceptable salt thereof. By “administer” is meant giving, supplying, dispensing, delivering, or applying a composition, agent, therapeutic and the like to a subject, or applying or bringing the composition and the like into contact with the subject. Administering or administration may be accomplished by any of a number of routes, such as, for example, without limitation, mucosal (e.g., intranasal, sublingual, intra-pulmonic, oral), topical, oral, subcutaneous, intramuscular, intraperitoneal, intravenous (IV), (injection), intrathecal, intramuscular, dermal, intradermal, intracranial, inhalation, intranasal, parenteral (e.g., intramuscular, subcutaneous, intradermal), rectal, intravaginal, or intraocular. By “agent” is meant any small molecule, small molecule chemical compound, antibody, nucleic acid molecule, peptide, polypeptide, or fragments, e.g., functional fragments, thereof. In various embodiments, an agent is an octavalent / pentavalent immunogen or vaccine of the disclosure. In some embodiments, an agent contains one or more polypeptides selected from Y2, Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 NG2, N2B (N2-B), Y4, NG3, N1I (N1-I), N2A, BC3, BC2, Z1, IAN8, Q6, sY2, sNG2, sN2B (sN2-B), sY4, sNG3, sN1I (sN1-I), sN2A, sBC3, sBC2, sZ1, sIAN8, and sQ6. By “alteration” is meant a change (increase or decrease) in the expression levels or activity of a gene or polypeptide as detected by standard art known methods such as those described herein. As used herein, an alteration includes a 5% change in expression levels, a 10% change in expression levels, a 25% change, a 40% change, or a 50% or greater change in expression levels. By “ameliorate” is meant decrease, reduce, diminish, suppress, attenuate, arrest, or stabilize the development or progression of a disease or pathological condition. By “analog” is meant a molecule that is not identical but has analogous functional or structural features. For example, a polypeptide analog retains the biological activity of a corresponding naturally-occurring polypeptide, while having certain biochemical modifications that enhance the analog's function relative to a naturally occurring polypeptide. Such biochemical modifications could increase the analog's protease resistance, membrane permeability, or half-life, without altering, for example, ligand binding. An analog may include an unnatural amino acid. By “antibody” is meant an immunoglobulin (Ig) molecule produced by B lymphoid cells and having a specific amino acid sequence. Antibodies are evoked or elicited in subjects (humans or other animals or mammals) following exposure to a specific antigen (immunogen). A subject capable of generating antibodies / immunoglobulin (i.e., an immune response) directed against a specific antigen / immunogen is said to be immunocompetent. Antibodies are characterized by reacting specifically with (e.g., binding to) an antigen or immunogen in some demonstrable way, antibody and antigen / immunogen each being defined in terms of the other. “Eliciting an antibody response” refers to the ability of an antigen, immunogen or other molecule to induce the production of antibodies. Antibodies are of different classes, e.g., IgM, IgG, IgA, IgE, IgD and subtypes or subclasses, e.g., IgG1, IgG2, IgG2a, IgG2b, IgG3, IgG4. An antibody / immunoglobulin response elicited in a subject can neutralize a pathogenic (e.g., infectious or disease-causing) agent by binding to epitopes (antigenic determinants) on the agent and blocking or inhibiting the activity of the agent, and / or by forming a binding complex with the agent that is cleared from the system (or body) of the subject, e.g., via the liver. As used herein, “broadly reactive” means that an immune response is elicited against a pathogen-derived antigen protein (e.g., a virus protein sequence, such as HA and / or NA) in a subject that is sufficient to block, inhibit, impede, neutralize, or prevent infection of a broad range of related pathogens (such as most or all influenza viruses within a specific subtype or Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 influenza viruses of other subtypes). In an embodiment, the subject is a mammalian subject. In an embodiment, the subject is an avian subject. By “antigen” is meant a compound, composition, or substance that can stimulate the production of antibodies or a T-cell response in an animal, including compositions that are injected or absorbed into an animal. In an embodiment, the antigen is a protein, a polypeptide, or a peptide antigen. An antigen reacts with the products of specific humoral or cellular immunity, including those induced by heterologous immunogens. In some embodiments of the disclosed compositions and methods, the antigen is an influenza hemagglutinin (HA) protein. In some embodiments of the disclosed compositions and methods, the antigen is a neuraminidase (NA) protein, e.g., an influenza virus NA protein. In many cases, an antigen that elicits or stimulates an immune response, e.g., an antibody or cellular immune response, in a subject is termed an “immunogen.” The term “antigenic drift” refers to a mechanism for variation in organisms or microorganisms such as viruses that involves the accumulation of mutations within the genes that code for antibody-binding sites (also called antigenic determinants or epitopes). This process results in a new strain of virus / virus particles that is not inhibited or blocked as effectively by antibodies that were originally generated against the antigens of virus strains prior to mutation, thus allowing the virus to spread more easily throughout a partially immune population. By way of example, antigenic drift occurs in both influenza A (IAV) and influenza B (IBV) viruses. In the context of a live virus, the term “attenuated” reflects a virus that is attenuated if its ability to infect a cell or subject and / or its ability to produce disease is reduced (for example, diminished, abrogated, or eliminated) compared to the ability of a wild-type virus to produce disease in the subject. In some embodiments, the ability to produce disease is diminished, abrogated, or eliminated. Typically, an attenuated virus retains at least some capacity to elicit an immune response following administration to an immunocompetent subject. In some cases, an attenuated virus can elicit a protective immune response without causing any signs or symptoms of infection. In some embodiments, the ability of an attenuated virus to cause disease or pathology in a subject is reduced at least about or equal to 5%, or at least about or equal to 10%, or at least about or equal to 25%, at least about or equal to 50%, at least about or equal to 75%, or at least about or equal to 80%, or at least about or equal to 85%, or at least about or equal to 90%, or at least about or equal to 95%, or greater, relative to the ability of a wild-type virus to cause disease or pathology in the subject. Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 The term “clade” refers to the different categorizations (often called subtypes) of the known influenza viruses, such as, e.g., the influenza A H3N2 virus. By way of example, viruses in an H3N2 clade are genetically related, but do not share the exact viral genome. As appreciated by the skilled practitioner, there are many clades and subclades of H3N2 virus subtypes designated in the art. By way of example, one clade is 3C.2a; subclades of this clade include 3C.2a.1, 3C.2a.2, 3C.2a.3 and 3C.2a.4. In addition, there are at least ten different clades of H5N1 virus subtypes designated in the art: clade 0 clade 1, clade 2, clade 3, clade 4, clade 5, clade 6, clade 7, clade 8 and clade 9 (Abdel-Ghafar et al., N Engl J Med 358:261-273, 2008). Clade 2 is further divided into sub-clades (including clade 2.1, clade 2.2, clade 2.3, clade 2.4 and clade 2.5). A “codon-optimized” nucleic acid refers to a nucleic acid sequence that has been altered such that the codons are optimal for expression in a particular system (such as a particular species or group of species). For example, a nucleic acid sequence can be optimized for expression in mammalian cells. Codon optimization does not alter the amino acid sequence of the encoded protein. In this disclosure, “comprises,” “comprising,” “containing” and “having” and the like can have the meaning ascribed to them in U.S. Patent law and can mean “ includes,” “including,” and the like; “consisting essentially of” or “consists essentially” likewise has the meaning ascribed in U.S. Patent law and the term is open-ended, allowing for the presence of more than that which is recited so long as basic or novel characteristics of that which is recited is not changed by the presence of more than that which is recited, but excludes prior art embodiments. Any embodiments specified as “comprising” a particular embodiment(s) or element(s) are also contemplated as “consisting of” or “consisting essentially of” the particular component(s) or element(s) in some embodiments. “Detect” refers to identifying the presence, absence or amount of an analyte, compound, agent, or substance to be detected. By “detectable label” is meant a compound, agent, or composition that, when linked to a molecule of interest, renders the latter detectable, e.g., via spectroscopic, photochemical, biochemical, immunochemical, chemiluminescent, or chemical means. Nonlimiting examples of useful detectable labels include radioactive isotopes, magnetic beads, metallic beads, colloidal particles, fluorescent dyes, electron-dense reagents, enzymes (for example, as commonly used in an ELISA), biotin, digoxigenin, or haptens. By “disease” is meant any condition, disorder, or pathology that damages or interferes with the normal function of a cell, tissue, or organ. Examples of diseases include those caused by influenza virus infection and the symptoms and adverse effects that are caused by infection of Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 the body with the H1, H2, H3, H5, H7, and / or IBV influenza virus. Influenza virus causes flu, bronchial diseases, and symptoms thereof, in infected individuals. By “effective amount” is meant the amount of an active therapeutic agent, composition, compound, biologic (e.g., a vaccine or therapeutic peptide, polypeptide, or polynucleotide) required to ameliorate, reduce, improve, abrogate, diminish, or eliminate the symptoms and / or effects of a disease, condition, or pathology relative to an untreated patient. In one embodiment, an effective amount is the amount of an antigen required to elicit an immune response. The effective amount of an immunogen or a composition comprising the immunogen, as used to practice the methods of therapeutic treatment of a disease, condition, or pathology, varies depending upon the manner of administration, the age, body weight, and general health of the subject. Ultimately, the attending physician or veterinarian will decide the appropriate amount and dosage regimen. Such amount is referred to as an “effective” amount. A “therapeutically effective amount” refers to a quantity of a specified agent sufficient to achieve a desired effect in a subject being treated with that agent. For example, this may be the amount of an influenza virus immunogen or vaccine, such as a pentavalent / octavalent composition / vaccine as described herein, useful for eliciting an immune response in a subject and / or for preventing infection by influenza virus. Ideally, in the context of the present disclosure, a therapeutically effective amount of an influenza vaccine or immunogenic composition is an amount sufficient to increase resistance to, prevent, ameliorate, reduce, and / or treat infection caused by influenza virus in a subject without causing a substantial cytotoxic effect in the subject. The effective amount of an immunogenic composition (or vaccine) useful for increasing resistance to, preventing, ameliorating, reducing, and / or treating infection in a subject depends on, for example, the subject being treated, the manner of administration of the therapeutic composition and other factors, as noted supra. In an embodiment, the immunogenic composition or vaccine is the pentavalent / octavalent composition / vaccine, or a formulation thereof, as described herein. By “fragment” is meant a portion of a polypeptide or nucleic acid molecule. A fragment or portion of a polypeptide or nucleic acid that retains functional activity is embraced herein. This portion contains, e.g., at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the entire length of the reference nucleic acid molecule or polypeptide. A fragment may contain 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100, 200, 300, 400, 500, 600, 700, 800, 900, or 1000 nucleotides or amino acids. A portion or fragment of a polypeptide may be a peptide. In the case of an antibody or immunoglobulin fragment, the fragment typically binds to the target antigen. Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 As used herein, a “formulation” generally refers to the pentavalent / octavalent composition / vaccine as described herein, which contains the five or eight, isolated, immunogenic HA and / or NA influenza virus antigen proteins, and one or more physiologically or pharmaceutically acceptable ingredients, reagents, or components. Such ingredients or reagents may include a physiologically or pharmaceutically acceptable carrier, excipient, or diluent as described herein. The formulation may also include other agents or components, such as, without limitation, an adjuvant or a mixture of adjuvants as described herein. In an embodiment, an adjuvant in the formulation is a cyclic dinucleotide. In an embodiment, the adjuvant is c-di- AMP. By “fusion protein” is meant a protein generated by expression of a nucleic acid (polynucleotide) sequence engineered from nucleic acid sequences encoding at least a portion of two different (heterologous) proteins or peptides. To create a fusion protein, the nucleic acid sequences must be in the same reading frame and contain no internal stop codons. For example, a fusion protein includes an influenza HA protein or NA protein fused to a heterologous protein. In embodiments, the nucleic acid is a polynucleotide and / or the two different proteins or peptides are heterologous. By “genetic vaccine” is meant an immunogenic composition comprising a polynucleotide encoding an antigen.” By “virus polypeptide,” such as an H1, H2, H3, H5, H7, and / or IBV influenza virus, is meant an amino acid sequence that is at least 85% identical, or at least 95% or greater identical, to an amino acid sequence of an antigen, e.g., an HA or NA antigen (e.g., an H1, H2, H3, H5, H7, IBV, N1, or N2 antigen), or a functional fragment thereof, capable of inducing an immune response against the virus, virus infection, and / or the symptoms thereof in an immunized subject. In embodiments, an influenza virus polypeptide comprises or consists of the amino acid sequences of the HA and NA antigen proteins, or a functional fragment thereof, contained in the pentavalent / octavalent composition / vaccine, as described infra (see also Table 4). By “virus polynucleotide” is meant a nucleic acid molecule encoding an influenza virus polypeptide, such as an H1, H2, H3, H5, H7, or IBV influenza virus antigen or antigen protein, as described herein. The term “Hemagglutinin (HA)” refers to a surface glycoprotein expressed by an influenza virus. HA mediates binding of the virus particle to a host cell and subsequent entry of the virus into the host cell. The nucleotide and amino acid sequences of numerous influenza HA proteins are known in the art and are publicly available, such as those deposited in the publicly accessible GenBank (NCBI) and UniProtKB databases. By way of nonlimiting example, a list of Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 GenBank Accession Nos. of H5N1 HA sequences may be found in US Patent Application Publication US 2015 / 0030628. A nonlimiting example of the amino acid sequence of the HA protein of influenza A virus (strain A / Puerto Rico / 8 / 1934 H1N1) is provided under UniProtKB Accession No. P03452 (HEMA_134A1). A nonlimiting example of the amino acid sequence of the HA protein of an influenza A, H3N2 virus, (A / Hong Kong / 1-4 / 1968(H3N2), is provided under Accession Number CY033017. Other non-limiting examples of HA proteins are described in the Examples herein. HA (along with neuraminidase (NA)) is one of the two major influenza virus antigenic proteins having antigenic determinants (epitopes) that are recognized and bound by antibodies / immunoglobulins. In embodiments, HA is an H1 HA protein antigen, an H2 HA protein antigen, an H3 HA protein antigen, an H5 HA protein antigen, an H7 HA protein antigen, or an IBV HA protein antigen. In an embodiment the HA protein antigen is a recombinant or recombinantly produced HA protein antigen. In embodiments, an NA antigen is an N1 or an N2 neuraminidase protein antigen. In embodiments, an HA protein antigen or fragment thereof may have at least about or equal to 85%, or at least about or equal to 90%, 95%, 98%, 99%, or greater, amino acid sequence identity to the amino acid sequence of a representative influenza A virus HA protein, an IBV HA protein, or a fragment thereof, such as the influenza virus HA proteins described herein. In various embodiments, an HA or NA antigen sequence of the disclosure is modified to not contain an N-terminal methionine. In an embodiment, an HA immunogenic protein antigen termed “Y2” is used in the pentavalent / octavalent immunogenic / vaccine composition and formulation described herein. Y2 is an H1 HA protein, which comprises or consists of the following full length amino acid sequence: Y2 (full length amino acid sequence):MKAILVVLLYTFTTANADTLCIGYHANNSTDTVDTVLEKNVTVTHSVNLLEDKHNGK LCKLRGVAPLHLGKCNIAGWILGNPECESLSTASSWSYIVETSNSDNGTCYPGDFINYEELREQ LSSVSSFERFEIFPKTSSWPNHDSNKGVTAACPHAGAKSFYKNLIWLVKKGNSYPKLSQSYIND KGKEVLVLWGIHHPSTTADQQSLYQNADAYVFVGTSRYSKKFKPEIAIRPKVRDQEGRMNYYWT LVEPGDKITFEATGNLVVPRYAFTMERNAGSGIIISDTPVHDCNTTCQTPEGAINTSLPFQNVH PITIGKCPKYVKSTKLRLATGLRNVPSIQSRGLFGAIAGFIEGGWTGMVDGWYGYHHQNEQGSG YAADLKSTQNAIDKITNKVNSVIEKMNTQFTAVGKEFNHLEKRIENLNKKVDDGFLDIWTYNAE LLVLLENERTLDYHDSNVKNLYEKVRNQLKNNAKEIGNGCFEFYHKCDNTCMESVKNGTYDYPK YSEEAKLNREKIDGV (SEQ ID NO: 1; Y2 HA full length amino acid sequence). Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 The following amino acids are sequences of portions of the stalk and transmembrane domain of the Y2 HA protein, which, in some cases, may be added to or included at the carboxy (COOH) terminus of the Y2 HA full length protein: KLESTRIYQILAIYSTVASSLVLVVSLGAISFWMCSNGSLQCRICI (SEQ ID NO: 21). The nucleic acid sequence encoding a full length form of the Y2 HA immunogenic protein antigen is provided, as follows: cgggaggaaaataaaaacaaccaaaatgaaagctattctggtcgtgctgctgtacacattcaca accgccaatgccgacaccctctgcatcggataccacgccaataactccaccgacaccgtggaca cagtgctggaaaagaacgtgacagtcacccactccgtgaatctgctggaggataagcacaacgg aaagctctgcaaactgaggggagtggcccctctgcatctgggcaaatgcaacattgccggctgg attctgggcaaccccgagtgcgagtctctgagcaccgccagcagctggagctacatcgtggaga cctccaactccgacaacggcacatgctaccccggcgacttcatcaactacgaggagctgagaga gcaactctcctccgtcagctcctttgaaaggttcgagatctttcccaagacatccagctggccc aaccacgattccaataagggcgtgacagctgcttgccctcatgccggcgccaagagcttttaca agaatctgatctggctcgtcaaaaaaggcaactcctaccccaagctgagccaatcctacatcaa cgacaagggcaaggaggtgctcgtgctctggggaatccaccatcctagcaccacagccgatcag cagagcctctatcagaacgccgatgcctacgtcttcgtcggcacctctagatactccaagaagt tcaagcccgagatcgctattaggcccaaggtgagagatcaagagggaagaatgaattactactg gacactggtggagcccggcgacaagatcaccttcgaagctaccggaaatctggtcgtgcccaga tatgccttcaccatggagaggaacgccggcagcggaatcattatctccgacacccccgtgcacg actgcaacaccacatgccagacccccgagggcgccatcaatacctctctgcccttccaaaacgt ccaccccatcaccattggcaaatgccccaagtacgtgaagagcaccaagctgaggctggctacc ggactgaggaatgtgcccagcattcagagcagaggactgtttggcgccatcgctggcttcatcg agggcggatggaccggaatggtggacggctggtacggataccaccaccagaacgagcaaggcag cggctatgccgccgatctgaagtccacccagaacgctatcgataagatcacaaacaaggtgaac agcgtgatcgagaaaatgaacacacagttcaccgccgtcggcaaggagttcaaccatctggaga agaggatcgagaatctgaacaagaaggtcgacgacggctttctggacatctggacctacaatgc tgagctgctggtgctgctcgagaacgaaagaaccctcgactaccacgacagcaacgtcaagaat ctgtacgaaaaagtcagaaatcagctcaagaacaacgccaaagagatcggcaacggctgctttg agttttaccacaagtgcgataacacatgcatggagagcgtgaagaacggaacctatgattaccc taaatacagcgaggaggccaagctgaatagagagaagatcgatggagtg (SEQ ID NO: 16; full length Y2 HA nucleic acid sequence). Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 The above-noted amino acid sequences of portions of the stalk and transmembrane domain of the Y2 HA protein, which, in some cases, may be added to or included at the carboxy (COOH) terminus of the Y2 HA full length protein are encoded by the following nucleic acids: aagctggagtccacaagaatctaccagattctggccatctacagcaccgtcgcctcctccctcg tgctcgtggtctctctgggagctatcagcttctggatgtgcagcaacggatctctgcaatgcag aatctgcatctgagattaggatttcagaaatataagaaaaacacaatag (SEQ ID NO: 22). The amino acid sequence of a soluble form of the Y2 HA immunogenic protein antigen is provided, as follows: Y2 (soluble HA amino acid sequence): MKAILVVLLYTFTTANADTLCIGYHANNSTDTVDTVLEKNVTVTHSVNLLEDKHNGKLCKLRGV APLHLGKCNIAGWILGNPECESLSTASSWSYIVETSNSDNGTCYPGDFINYEELREQLSSVSSF ERFEIFPKTSSWPNHDSNKGVTAACPHAGAKSFYKNLIWLVKKGNSYPKLSQSYINDKGKEVLV LWGIHHPSTTADQQSLYQNADAYVFVGTSRYSKKFKPEIAIRPKVRDQEGRMNYYWTLVEPGDK ITFEATGNLVVPRYAFTMERNAGSGIIISDTPVHDCNTTCQTPEGAINTSLPFQNVHPITIGKC PKYVKSTKLRLATGLRNVPSIQSRGLFGAIAGFIEGGWTGMVDGWYGYHHQNEQGSGYAADLKS TQNAIDKITNKVNSVIEKMNTQFTAVGKEFNHLEKRIENLNKKVDDGFLDIWTYNAELLVLLEN ERTLDYHDSNVKNLYEKVRNQLKNNAKEIGNGCFEFYHKCDNTCMESVKNGTYDYPKYSEEAKL NREKIDGV (SEQ ID NO: 6; soluble Y2 (sY2) amino acid sequence). The following amino acid additions, including a histidine (His) tag (e.g., six consecutive histidine amino acids), may be added to or included at the carboxy (COOH) terminus of the Y2 HA soluble protein: GTGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGLNDIFEAQKIEWHEGHHHHHH (SEQ ID NO: 23). The nucleic acid sequence encoding the soluble form of the Y2 HA immunogenic protein antigen is provided, as follows: aagcttatgaaggccattctggtggtgctgctgtacaccttcaccacagccaacgccgacacac tgtgcatcggctatcacgccaacaattccaccgacacagtcgacaccgtgctggagaagaacgt gaccgtcacccacagcgtcaatctgctggaagacaagcacaacggaaagctgtgcaagctgagg ggagtggcccctctgcatctcggaaagtgcaatatcgccggctggattctgggcaaccccgaat gtgagtctctgagcaccgccagcagctggtcctacatcgtcgaaaccagcaactccgataacgg cacatgctaccccggcgactttatcaactacgaggagctgagggagcagctctcctccgtgagc agcttcgaaaggttcgagatcttccctaagaccagcagctggcctaaccacgattccaacaaag gcgtcaccgctgcttgtccccatgccggcgccaagagcttttacaagaatctgatctggctggt gaagaagggcaacagctaccctaagctcagccagagctatatcaacgacaagggcaaagaggtg Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 ctggtgctgtggggaatccaccatccctccaccaccgctgaccagcagtctctgtatcaaaacg ccgacgcctacgtgttcgtgggcacctctagatacagcaaaaagtttaagcccgagattgccat tagacctaaggtgagggaccaagagggaagaatgaattactactggacactggtcgagcccggc gacaagatcacattcgaagccaccggcaatctggtggtgcctaggtatgccttcaccatggaga gaaacgctggctccggcatcatcattagcgatacacccgtgcacgactgtaacacaacatgcca gacccccgagggcgccatcaatacctctctgcccttccagaacgtgcatcccatcaccatcggc aaatgtcccaagtacgtgaagtccaccaagctgagactggctaccggactgagaaatgtgcctt ccatccagtccagaggactgtttggcgccattgccggattcatcgaaggaggatggaccggcat ggtcgacggatggtacggctaccatcaccaaaacgagcaaggcagcggatacgctgccgatctg aagtccacccagaacgccatcgacaaaatcaccaataaagtgaactccgtgatcgagaaaatga acacccagttcaccgccgtgggcaaggagttcaaccatctggagaagaggatcgagaatctgaa caagaaggtggacgatggcttcctcgacatctggacctacaacgccgagctgctcgtgctgctg gagaacgagagaacactggattaccacgacagcaacgtcaagaatctgtacgagaaggtgagaa accagctcaagaacaacgctaaggagatcggcaacggctgtttcgagttttaccacaaatgcga caacacatgcatggagagcgtgaagaacggcacctacgactaccctaagtattccgaggaggcc aagctgaatagagagaagatcgacggagtg (SEQ ID NO: 11; soluble Y2 (sY2) nucleic acid sequence). The above-noted amino acid additions, including a His tag (e.g., six consecutive histidine amino acids), that may be added to or included at the carboxy (COOH) terminus of the Y2 HA soluble protein are encoded by the following nucleic acids: ggcaccggctacattcccgaggcccccagagatggacaagcctacgtgaggaaagacggcgagt gggtgctgctgtccacctttctgggaagcggactgaacgacatctttgaggcccagaagatcga gtggcatgagggccaccaccatcaccaccattgatgaggatcc (SEQ ID NO: 24). In an embodiment, an HA immunogenic protein antigen termed “NG2” is used in the pentavalent / octavalent immunogenic / vaccine composition and formulation described herein. NG2 is an H3 HA protein, which comprises or consists of the following full length amino acid sequence: NG2 – (full length HA amino acid sequence): MKTIIALSYILCLVFAQKIPGNDNSTATLCLGHHAVPNGTIVKTITNDRIEVTNATELVQNSSI GEICDSPHQILDGENCTLIDALLGDPQCDGFQNKKWDLFVERSKAYSNCYPYDVPDYASLRSLV ASSGTLEFKNESFNWTGVTQNGTSSACIRGSSSSFFSRLNWLTHLNYTYPALNVTMPNNEQFDK LYIWGVHHPGTDKDQIFLYAQSSGRITVSTKRSQQAVIPNIGSRPRIRDIPSRISIYWTIVKPG DILLINSTGNLIAPRGYFKIRSGKSSIMRSDAPIGKCKSECITPNGSIPNDKPFQNVNRITYGA CPRYVKQSTLKLATGMRNVPEKQTRGIFGAIAGFIENGWEGMVDGWYGFRHQNSEGRGQAADLK Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 STQAAIDQINGKLNRLIGKTNEKFHQIEKEFSEVEGRIQDLEKYVEDTKIDLWSYNAELLVALE NQHTIDLTDSEMNKLFEKTKKQLRENAEDMGNGCFKIYHKCDNACIGSIRNGTYDHNVYRDEAL NNRFQIKGVELKSGYKD (SEQ ID NO: 2; NG2 HA full length amino acid sequence). The following amino acids are sequences of portions of the stalk and transmembrane domain of the NG2 HA protein, which, in some cases, may be added to or included at the carboxy (COOH) terminus of the NG2 HA full length protein: WILWISFAISCFLLCVALLGFIMWACQKGNIRCNICI (SEQ ID NO: 25). The nucleic acid sequence encoding a full length form of the NG2 HA immunogenic protein antigen is provided, as follows: atgaaaaccattattgcgctgagctatattctgtgcctggtgtttgcgcagaaaattcc gggcaacgataacagcaccgcgaccctgtgcctgggccatcatgcggtgccgaacggcaccatt gtgaaaaccattaccaacgatcgcattgaagtgaccaacgcgaccgaactggtgcagaacagca gcattggcgaaatttgcgatagcccgcatcagattctggatggcgaaaactgcaccctgattga tgcgctgctgggcgatccgcagtgcgatggctttcagaacaaaaaatgggatctgtttgtggaa cgcagcaaagcgtatagcaactgctatccgtatgatgtgccggattatgcgagcctgcgcagcc tggtggcgagcagcggcaccctggaatttaaaaacgaaagctttaactggaccggcgtgaccca gaacggcaccagcagcgcgtgcattcgcggcagcagcagcagcttttttagccgcctgaactgg ctgacccatctgaactatacctatccggcgctgaacgtgaccatgccgaacaacgaacagtttg ataaactgtatatttggggcgtgcatcatccgggcaccgataaagatcagatttttctgtatgc gcagagcagcggccgcattaccgtgagcaccaaacgcagccagcaggcggtgattccgaacatt ggcagccgcccgcgcattcgcgatattccgagccgcattagcatttattggaccattgtgaaac cgggcgatattctgctgattaacagcaccggcaacctgattgcgccgcgcggctattttaaaat tcgcagcggcaaaagcagcattatgcgcagcgatgcgccgattggcaaatgcaaaagcgaatgc attaccccgaacggcagcattccgaacgataaaccgtttcagaacgtgaaccgcattacctatg gcgcgtgcccgcgctatgtgaaacagagcaccctgaaactggcgaccggcatgcgcaacgtgcc ggaaaaacagacccgcggcatttttggcgcgattgcgggctttattgaaaacggctgggaaggc atggtggatggctggtatggctttcgccatcagaacagcgaaggccgcggccaggcggcggatc tgaaaagcacccaggcggcgattgatcagattaacggcaaactgaaccgcctgattggcaaaac caacgaaaaatttcatcagattgaaaaagaatttagcgaagtggaaggccgcattcaggatctg gaaaaatatgtggaagataccaaaattgatctgtggagctataacgcggaactgctggtggcgc tggaaaaccagcataccattgatctgaccgatagcgaaatgaacaaactgtttgaaaaaaccaa aaaacagctgcgcgaaaacgcggaagatatgggcaacggctgctttaaaatttatcataaatgc gataacgcgtgcattggcagcattcgcaacggcacctatgatcataacgtgtatcgcgatgaag cgctgaacaaccgctttcagattaaaggcgtggaactgaaaagcggctataaagat Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 (SEQ ID NO: 17; full length NG2 HA nucleic acid sequence). The above-noted amino acid sequences of portions of the stalk and transmembrane domain of the NG2 HA protein, which, in some cases, may be added to or included at the carboxy (COOH) terminus of the NG2 HA full length protein are encoded by the following nucleic acids: tggattctgtggattagctttgcgattagctgctttctgctgtgcgtggcgctgctgggcttta ttatgtgggcgtgccagaaaggcaacattcgctgcaacatttgcatt (SEQ ID NO: 26). The amino acid sequence of a soluble form of the NG2 HA immunogenic protein antigen (sNG2) is provided, as follows: NG2 (soluble HA amino acid sequence): MKTIIALSYILCLVFAQKIPGNDNSTATLCLGHHAVPNGTIVKTITNDRIEVTNATELVQNSSI GEICDSPHQILDGENCTLIDALLGDPQCDGFQNKKWDLFVERSKAYSNCYPYDVPDYASLRSLV ASSGTLEFKNESFNWTGVTQNGTSSACIRGSSSSFFSRLNWLTHLNYTYPALNVTMPNNEQFDK LYIWGVHHPGTDKDQIFLYAQSSGRITVSTKRSQQAVIPNIGSRPRIRDIPSRISIYWTIVKPG DILLINSTGNLIAPRGYFKIRSGKSSIMRSDAPIGKCKSECITPNGSIPNDKPFQNVNRITYGA CPRYVKQSTLKLATGMRNVPEKQTRGIFGAIAGFIENGWEGMVDGWYGFRHQNSEGRGQAADLK STQAAIDQINGKLNRLIGKTNEKFHQIEKEFSEVEGRIQDLEKYVEDTKIDLWSYNAELLVALE NQHTIDLTDSEMNKLFEKTKKQLRENAEDMGNGCFKIYHKCDNACIGSIRNGTYDHNVYRDEAL NNRFQIKGVELKSGYKD (SEQ ID NO: 7; soluble NG2 (sNG2) amino acid sequence). The following amino acid additions, including a His tag (e.g., six consecutive histidine amino acids), may be added to or included at the carboxy (COOH) terminus of the sNG2 HA protein: GSGYIPEAPRDGQAYVRKDGEWVLLSTFLGLNDIFEAQKIEWHEGHHHHHHGS (SEQ ID NO: 27). The nucleic acid sequence encoding the soluble form of the NG2 HA immunogenic protein antigen is provided, as follows: aagcttatgaaaacaatcatcgctctgtcctacattctgtgtctggtgttcgcccagaagattc ccggcaatgacaacagcaccgctacactgtgcctcggccatcacgccgtgcctaacggcaccat cgtgaaaaccattaccaatgatagaatcgaggtgaccaacgccaccgagctcgtccagaacagc agcatcggcgaaatctgcgattcccctcatcagatcctcgacggcgagaactgcaccctcattg atgctctgctcggagacccccaatgcgatggcttccagaacaagaagtgggatctgttcgtgga aaggagcaaggcctatagcaactgctacccctatgacgtgcccgattatgcctctctgagatct ctggtcgcttcctccggaacactggagttcaagaacgagtccttcaactggaccggagtgaccc aaaatggaaccagcagcgcttgcattaggggaagctccagctccttcttctccagactgaactg Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 gctcacccatctgaactatacctaccccgctctgaatgtcaccatgcccaacaatgagcagttc gacaaactgtacatctggggcgtgcatcatcccggcaccgacaaagaccagatctttctgtacg cccagtccagcggaagaatcaccgtgagcaccaagagaagccagcaagccgtgatccctaatat cggctctagacctagaatcagagacatcccctctagaatctccatctactggaccattgtgaaa cccggcgacattctgctgattaactccaccggcaacctcattgcccctaggggctacttcaaaa ttagatccggcaagagcagcattatgaggtccgacgctcctatcggaaagtgtaaatccgagtg catcacccccaatggctccatccccaatgataagcccttccagaacgtcaataggatcacctat ggcgcttgccctagatacgtcaaacagtccacactgaagctcgccaccggcatgaggaatgtcc ccgagaagcagaccagaggcattttcggcgctatcgctggctttatcgagaacggctgggaagg catggtcgacggctggtacggctttagacatcaaaattccgagggaagaggccaagccgctgac ctcaagtccacccaagccgccatcgaccagatcaacggcaagctcaatagactcatcggcaaga caaacgaaaagtttcatcaaattgaaaaggagttctccgaggtcgagggaagaattcaagatct ggagaaatacgtggaggacaccaagatcgatctgtggagctataacgctgagctcctcgtggcc ctcgaaaaccagcacacaatcgatctcaccgactccgagatgaataagctcttcgagaagacaa aaaagcagctcagagagaatgccgaggatatgggcaacggctgcttcaagatctaccacaagtg tgacaatgcttgcatcggcagcatcagaaacggaacctacgaccacaacgtctacagagacgag gctctcaacaatagattccagatcaagggagtggagctcaagagcggctacaaggat (SEQ ID NO: 12; soluble NG2 (sNG2) nucleic acid sequence). The above-noted amino acid additions, including a His tag (e.g., six consecutive histidine amino acids), that may be added to or included at the carboxy (COOH) terminus of the NG2 soluble HA protein are encoded by the following nucleic acids which would be present at the 3' terminus of the above nucleic acid sequence: ggaagcggctatatccccgaggctcctagagatggccaagcctacgtgaggaaagacggcgagt gggtgctgctgtccacctttctcggactgaacgacatctttgaggcccagaagatcgagtggca tgagggacatcaccaccatcaccatggatcc (SEQ ID NO: 28). In an embodiment, an HA immunogenic protein antigen termed “BC2” (“COBRA BC2”) is used in the pentavalent / octavalent immunogenic / vaccine composition and formulation described herein. BC2 is an IBV HA protein, which comprises or consists of the following full length amino acid sequence: BC2 (IBV) COBRA – (full length HA amino acid sequence, where the stalk and transmembrane domains are underlined):MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHF ANLKGTKTRGKLCPKCLNCTDLDVALGRPKCMGTIPSAKASILHEVRPVTSGCFPIMHDRTKIR QLPNLLRGYENIRLSTHNVINAEKAPGGPYRIGTSGSCPNVTNGNGFFATMAWAVPKNDNNKTA Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 TNPLTVEVPYICTEGEDQITVWGFHSDNETQMKKLYGDSKPQKFTSSANGVTTHYVSQIGGFPN QTEDGGLPQSGRIVVDYMVQKSGKTGTIVYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLH EKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGW EGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEIL ELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVDIGNGCFETKH KCNQTCLDRIAAGTFNAGEFSLPTFDSLNITAASLNDDGLDNHTILLYYSTAASSLAVTLMIAI FIVYMVSRDNVSCSICL (SEQ ID NO: 3; BC2 HA full length amino acid sequence). The above, underlined amino acids at the carboxy (COOH) terminus of the sequence are sequences of portions of the stalk and transmembrane domain of the BC2 HA protein, which, in some cases, may be added to or included at the carboxy terminus of the BC2 HA full length protein. The stalk and transmembrane domain amino acid sequences are as follows: AASLNDDGLDNHTILLYYSTAASSLAVTLMIAIFIVYMVSRDNVSCSICL (SEQ ID NO: 29). In embodiments, the stalk and transmembrane domains of BC2 are removed. An embodiment of a nucleic acid sequence encoding the full length form of the BC2 HA immunogenic protein antigen is provided below. The underlined sequence at the 3' end indicates stalk and transmembrane domain coding regions. atgaaggccatcatcgtgctgctgatggtggtgaccagcaacgccgacagaatctgcaccggca tcaccagcagcaacagcccccacgtggtgaagaccgccacccagggcgaggtgaacgtgaccgg cgtgatccccctgaccaccacccccaccaagagccacttcgccaacctgaagggcaccaagacc agaggcaagctgtgccccaagtgcctgaactgcaccgacctggacgtggccctgggcagaccca agtgcatgggcaccatccccagcgccaaggccagcatcctgcacgaggtgagacccgtgaccag cggctgcttccccatcatgcacgacagaaccaagatcagacagctgcccaacctgctgagaggc tacgagaacatcagactgagcacccacaacgtgatcaacgccgagaaggcccccggcggcccct acagaatcggcaccagcggcagctgccccaacgtgaccaacggcaacggcttcttcgccaccat ggcctgggccgtgcccaagaacgacaacaacaagaccgccaccaaccccctgaccgtggaggtg ccctacatctgcaccgagggcgaggaccagatcaccgtgtggggcttccacagcgacaacgaga cccagatgaagaagctgtacggcgacagcaagccccagaagttcaccagcagcgccaacggcgt gaccacccactacgtgagccagatcggcggcttccccaaccagaccgaggacggcggcctgccc cagagcggcagaatcgtggtggactacatggtgcagaagagcggcaagaccggcaccatcgtgt accagagaggcatcctgctgccccagaaggtgtggtgcgccagcggcagaagcaaggtgatcaa gggcagcctgcccctgatcggcgaggccgactgcctgcacgagaagtacggcggcctgaacaag agcaagccctactacaccggcgagcacgccaaggccatcggcaactgccccatctgggtgaaga cccccctgaagctggccaacggcaccaagtacagaccccccgccaagctgctgaaggagagagg cttcttcggcgccatcgccggcttcctggagggcggctgggagggcatgatcgccggctggcac Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 ggctacaccagccacggcgcccacggcgtggccgtggccgccgacctgaagagcacccaggagg ccatcaacaagatcaccaagaacctgaacagcctgagcgagctggaggtgaagaacctgcagag actgagcggcgccatggacgagctgcacaacgagatcctggagctggacgagaaggtggacgac ctgagagccgacaccatcagcagccagatcgagctggccgtgctgctgagcaacgagggcatca tcaacagcgaggacgagcacctgctggccctggagagaaagctgaagaagatgctgggccccag cgccgtggacatcggcaacggctgcttcgagaccaagcacaagtgcaaccagacctgcctggac agaatcgccgccggcaccttcaacgccggcgagttcagcctgcccaccttcgacagcctgaaca tcaccgccgccagcctgaacgacgacggcctggacaaccacaccatcctgctgtactacagcac cgccgccagcagcctggccgtgaccctgatgatcgccatcttcatcgtgtacatggtgagcaga gacaacgtgagctgcagcatctgcctg (SEQ ID NO: 18; BC2 HA full length nucleic acid sequence). The nucleic acid sequence that encodes the stalk and transmembrane domain amino acid sequences and which may be removed in the amino acid sequence of the BC2 HA full length protein, is provided below as follows: gccgccagcctgaacgacgacggcctggacaaccacaccatcctgctgtactacagcaccgccg ccagcagcctggccgtgaccctgatgatcgccatcttcatcgtgtacatggtgagcagagacaa cgtgagctgcagcatctgcctg (SEQ ID NO: 30). The amino acid sequence of a soluble form of the BC2 COBRA HA immunogenic protein antigen is provided, as follows: BC2 (soluble HA amino acid sequence):MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFA NLKGTKTRGKLCPKCLNCTDLDVALGRPKCMGTIPSAKASILHEVRPVTSGCFPIMHDRTKIRQ LPNLLRGYENIRLSTHNVINAEKAPGGPYRIGTSGSCPNVTNGNGFFATMAWAVPKNDNNKTAT NPLTVEVPYICTEGEDQITVWGFHSDNETQMKKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQ TEDGGLPQSGRIVVDYMVQKSGKTGTIVYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHE KYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWE GMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILE LDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVDIGNGCFETKHK CNQTCLDRIAAGTFNAGEFSLPTFDSLNIT (SEQ ID NO: 8; soluble BC2 (sBC2) amino acid sequence). The following amino acid additions, including a His tag (e.g., six consecutive histidine amino acids), may be added to or included at the carboxy (COOH) terminus of the BC2 soluble HA protein: GSGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGLNDIFEAQKIEWHEGHHHHHH (SEQ ID NO: 31). Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 An embodiment of a nucleic acid sequence encoding the soluble form of the BC2 HA immunogenic protein antigen is provided, as follows: atgaaggccatcatcgtgctgctgatggtggtgaccagcaacgccgacagaatctgcaccggca tcaccagcagcaacagcccccacgtggtgaagaccgccacccagggcgaggtgaacgtgaccgg cgtgatccccctgaccaccacccccaccaagagccacttcgccaacctgaagggcaccaagacc agaggcaagctgtgccccaagtgcctgaactgcaccgacctggacgtggccctgggcagaccca agtgcatgggcaccatccccagcgccaaggccagcatcctgcacgaggtgagacccgtgaccag cggctgcttccccatcatgcacgacagaaccaagatcagacagctgcccaacctgctgagaggc tacgagaacatcagactgagcacccacaacgtgatcaacgccgagaaggcccccggcggcccct acagaatcggcaccagcggcagctgccccaacgtgaccaacggcaacggcttcttcgccaccat ggcctgggccgtgcccaagaacgacaacaacaagaccgccaccaaccccctgaccgtggaggtg ccctacatctgcaccgagggcgaggaccagatcaccgtgtggggcttccacagcgacaacgaga cccagatgaagaagctgtacggcgacagcaagccccagaagttcaccagcagcgccaacggcgt gaccacccactacgtgagccagatcggcggcttccccaaccagaccgaggacggcggcctgccc cagagcggcagaatcgtggtggactacatggtgcagaagagcggcaagaccggcaccatcgtgt accagagaggcatcctgctgccccagaaggtgtggtgcgccagcggcagaagcaaggtgatcaa gggcagcctgcccctgatcggcgaggccgactgcctgcacgagaagtacggcggcctgaacaag agcaagccctactacaccggcgagcacgccaaggccatcggcaactgccccatctgggtgaaga cccccctgaagctggccaacggcaccaagtacagaccccccgccaagctgctgaaggagagagg cttcttcggcgccatcgccggcttcctggagggcggctgggagggcatgatcgccggctggcac ggctacaccagccacggcgcccacggcgtggccgtggccgccgacctgaagagcacccaggagg ccatcaacaagatcaccaagaacctgaacagcctgagcgagctggaggtgaagaacctgcagag actgagcggcgccatggacgagctgcacaacgagatcctggagctggacgagaaggtggacgac ctgagagccgacaccatcagcagccagatcgagctggccgtgctgctgagcaacgagggcatca tcaacagcgaggacgagcacctgctggccctggagagaaagctgaagaagatgctgggccccag cgccgtggacatcggcaacggctgcttcgagaccaagcacaagtgcaaccagacctgcctggac agaatcgccgccggcaccttcaacgccggcgagttcagcctgcccaccttcgacagcctgaaca tcacc (SEQ ID NO: 13; soluble BC2 (sBC2) nucleic acid sequence). The following amino acid sequence, or a fragment thereof, optionally including a His tag (e.g., six consecutive histidine amino acids), may be added to or included at the carboxy (COOH) terminus of the BC2 HA soluble protein: GSGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGLNDIFEAQKIEWHEGHHHHHH (SEQ ID NO: 31). Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 The 3' nucleic acid sequence encoding amino acid additions, including a His tag (e.g., six consecutive histidine amino acids), which may be added to or included at the carboxy terminus of the sBC2 protein is as follows: Ggcagcggctacatccccgaggcccccagagacggccaggcctacgtgagaaaggacggcgagt gggtgctgctgagcaccttcctgggcagcggcctgaacgacatcttcgaggcccagaagatcga gtggcacgagggccaccaccaccaccaccac (SEQ ID NO: 32). In an embodiment, an HA immunogenic protein antigen termed “BC3” is used in the octavalent / pentavalent immunogenic / vaccine composition and formulation described herein. BC3 is an IBV HA protein, which comprises or consists of the following full length amino acid sequence, or a fragment thereof: BC3 (full length amino acid sequence, where the stalk and transmembrane domains are underlined): MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTKT RGKLCPKCLNCTDLDVALGRPKCTGNIPSAKVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRG YEHIRLSTHNVINAEKAPGGPYKIGTSGSCPNVTNGNGFFATMAWAVPKNDNNKTATNPLTIEV PYICTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLP QSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNK SKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWH GYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDD LRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLD RIAAGTFDAGEFSLPTFDSLNITAASLNDDGLDNHTILLYYSTAASSLAVTLMIAIFVVYMVSR DNVSCSICL (SEQ ID NO: 69; BC3 HA full length amino acid sequence). In embodiments, the stalk and transmembrane domains of BC3 are removed. An embodiment of a nucleic acid sequence encoding the full-length BC3 HA immunogenic protein antigen is provided as follows: BC3 (full length nucleotide sequence, where nucleotides encoding the stalk and transmembrane domains are underlined): atgaaggccatcatcgtgctgctgatggtggtgaccagcaacgccgacagaatctgcaccggca tcaccagcagcaacagcccccacgtggtgaagaccgccacccagggcgaggtgaacgtgaccgg cgtgatccccctgaccaccacccccaccaagagccacttcgccaacctgaagggcaccaagacc agaggcaagctgtgccccaagtgcctgaactgcaccgacctggacgtggccctgggcagaccca agtgcaccggcaacatccccagcgccaaggtgagcatcctgcacgaggtgagacccgtgaccag cggctgcttccccatcatgcacgacagaaccaagatcagacagctgcccaacctgctgagaggc tacgagcacatcagactgagcacccacaacgtgatcaacgccgagaaggcccccggcggcccct Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 acaagatcggcaccagcggcagctgccccaacgtgaccaacggcaacggcttcttcgccaccat ggcctgggccgtgcccaagaacgacaacaacaagaccgccaccaaccccctgaccatcgaggtg ccctacatctgcaccgagggcgaggaccagatcaccgtgtggggcttccacagcgacaacgaga cccagatggccaagctgtacggcgacagcaagccccagaagttcaccagcagcgccaacggcgt gaccacccactacgtgagccagatcggcggcttccccaaccagaccgaggacggcggcctgccc cagagcggcagaatcgtggtggactacatggtgcagaagagcggcaagaccggcaccatcacct accagagaggcatcctgctgccccagaaggtgtggtgcgccagcggcagaagcaaggtgatcaa gggcagcctgcccctgatcggcgaggccgactgcctgcacgagaagtacggcggcctgaacaag agcaagccctactacaccggcgagcacgccaaggccatcggcaactgccccatctgggtgaaga cccccctgaagctggccaacggcaccaagtacagaccccccgccaagctgctgaaggagagagg cttcttcggcgccatcgccggcttcctggagggcggctgggagggcatgatcgccggctggcac ggctacaccagccacggcgcccacggcgtggccgtggccgccgacctgaagagcacccaggagg ccatcaacaagatcaccaagaacctgaacagcctgagcgagctggaggtgaagaacctgcagag actgagcggcgccatggacgagctgcacaacgagatcctggagctggacgagaaggtggacgac ctgagagccgacaccatcagcagccagatcgagctggccgtgctgctgagcaacgagggcatca tcaacagcgaggacgagcacctgctggccctggagagaaagctgaagaagatgctgggccccag cgccgtggagatcggcaacggctgcttcgagaccaagcacaagtgcaaccagacctgcctggac agaatcgccgccggcaccttcgacgccggcgagttcagcctgcccaccttcgacagcctgaaca tcaccgccgccagcctgaacgacgacggcctggacaaccacaccatcctgctgtactacagcac cgccgccagcagcctggccgtgaccctgatgatcgccatcttcgtggtgtacatggtgagcaga gacaacgtgagctgcagcatctgcctg (SEQ ID NO: 70; full-length BC3 HA nucleotide sequence). The amino acid sequence of a soluble form of the BC3 HA immunogenic protein antigen is provided, as follows: BC3 (soluble HA amino acid sequence): MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTKT RGKLCPKCLNCTDLDVALGRPKCTGNIPSAKVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRG YEHIRLSTHNVINAEKAPGGPYKIGTSGSCPNVTNGNGFFATMAWAVPKNDNNKTATNPLTIEV PYICTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLP QSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNK SKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWH GYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDD LRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLD RIAAGTFDAGEFSLPTFDSLNIT (SEQ ID NO: 71; soluble BC3 (sBC3) amino acid sequence). Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 An embodiment of a nucleic acid sequence encoding the soluble form of the BC3 HA immunogenic protein antigen is provided, as follows: BC3 (soluble HA nucleotide sequence): atgaaggccatcatcgtgctgctgatggtggtgaccagcaacgccgacagaatctgcaccggca tcaccagcagcaacagcccccacgtggtgaagaccgccacccagggcgaggtgaacgtgaccgg cgtgatccccctgaccaccacccccaccaagagccacttcgccaacctgaagggcaccaagacc agaggcaagctgtgccccaagtgcctgaactgcaccgacctggacgtggccctgggcagaccca agtgcaccggcaacatccccagcgccaaggtgagcatcctgcacgaggtgagacccgtgaccag cggctgcttccccatcatgcacgacagaaccaagatcagacagctgcccaacctgctgagaggc tacgagcacatcagactgagcacccacaacgtgatcaacgccgagaaggcccccggcggcccct acaagatcggcaccagcggcagctgccccaacgtgaccaacggcaacggcttcttcgccaccat ggcctgggccgtgcccaagaacgacaacaacaagaccgccaccaaccccctgaccatcgaggtg ccctacatctgcaccgagggcgaggaccagatcaccgtgtggggcttccacagcgacaacgaga cccagatggccaagctgtacggcgacagcaagccccagaagttcaccagcagcgccaacggcgt gaccacccactacgtgagccagatcggcggcttccccaaccagaccgaggacggcggcctgccc cagagcggcagaatcgtggtggactacatggtgcagaagagcggcaagaccggcaccatcacct accagagaggcatcctgctgccccagaaggtgtggtgcgccagcggcagaagcaaggtgatcaa gggcagcctgcccctgatcggcgaggccgactgcctgcacgagaagtacggcggcctgaacaag agcaagccctactacaccggcgagcacgccaaggccatcggcaactgccccatctgggtgaaga cccccctgaagctggccaacggcaccaagtacagaccccccgccaagctgctgaaggagagagg cttcttcggcgccatcgccggcttcctggagggcggctgggagggcatgatcgccggctggcac ggctacaccagccacggcgcccacggcgtggccgtggccgccgacctgaagagcacccaggagg ccatcaacaagatcaccaagaacctgaacagcctgagcgagctggaggtgaagaacctgcagag actgagcggcgccatggacgagctgcacaacgagatcctggagctggacgagaaggtggacgac ctgagagccgacaccatcagcagccagatcgagctggccgtgctgctgagcaacgagggcatca tcaacagcgaggacgagcacctgctggccctggagagaaagctgaagaagatgctgggccccag cgccgtggagatcggcaacggctgcttcgagaccaagcacaagtgcaaccagacctgcctggac agaatcgccgccggcaccttcgacgccggcgagttcagcctgcccaccttcgacagcctgaaca tcacc (SEQ ID NO: 72; soluble BC3 (sBC3) nucleic acid sequence). The following amino acid sequence, or a fragment thereof, optionally including a His tag (e.g., six consecutive histidine amino acids), may be added to or included at the carboxy (COOH) terminus of the BC3 HA soluble protein: GSGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGLNDIFEAQKIEWHEGHHHHHH (SEQ ID NO: 31). Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 The above-noted amino acid sequence, including a His tag (e.g., six consecutive histidine amino acids), that may be added to or included at the carboxy (COOH) terminus of the BC3 HA soluble protein may be encoded by the following nucleic acid sequence: ggcagcggctacatccccgaggcccccagagacggccaggcctacgtgagaaaggacggcgagt gggtgctgctgagcaccttcctgggcagcggcctgaacgacatcttcgaggcccagaagatcga gtggcacgagggccaccaccaccaccaccac (SEQ ID NO: 32). In an embodiment, an HA immunogenic protein antigen termed “IAN8” is used in the octavalent / pentavalent immunogenic / vaccine composition and formulation described herein. IAN8 is an H5 HA protein, which comprises or consists of the following full length amino acid sequence, or a fragment thereof: IAN8 (full length amino acid sequence, where the stalk and transmembrane domains are underlined): MEKIVLLFAIVSLVKSDQICIGYHANNSTEQVDTIMEKNVTVTHAQDILEKTHNGKLCDLNGVK PLILKDCSVAGWLLGNPMCDEFINVPEWSYIVEKANPANDLCYPGNFNDYEELKHLLSRINHFE KIQIIPKSSWSDHEASLGVSAACPYQGNSSFFRNVVWLIKKNNAYPTIKKSYNNTNQEDLLVLW GIHHPNDAAEQTRLYQNPTTYISVGTSTLNQRLVPKIATRSKVNGQSGRMDFFWTILKPNDAIH FESNGNFIAPEYAYKIVKKGDSTIMKSELEYGNCNTKCQTPIGAINSSMPFHNIHPLTIGECPK YVKSNKLVLATGLRNSPQNSPQRERRRKRGLFGAIAGFIEGGWQGMVDGWYGYHHSNEQGSGYA ADKESTQKAIDGVTNKVNSIIDKMNTQFEAVGREFNNLERRIENLNKKMEDGFLDVWTYNAELL VLMENERTLDFHDSNVKNLYDKVRLQLKDNAKELGNGCFEFYHKCNNECMESVRNGTYDYPQYS EEARLKREEISGVKLESIGIYQILSIYSTVASSLVLAIMMAGLSLWMCSNGSLQCRICI (SEQ ID NO: 34; IAN8 HA full length amino acid sequence). In embodiments, the stalk and transmembrane domains of IAN8 are removed. An embodiment of a nucleic acid sequence encoding the full-length IAN8 HA immunogenic protein antigen is provided as follows: IAN8 (full length nucleotide sequence, where nucleotides encoding the stalk and transmembrane domains are underlined): atggaaaaaattgtgctgctgtttgcgattgtgagcctggtgaaaagcgatcagatttgcattg gctatcatgcgaacaacagcaccgaacaggtggataccattatggaaaaaaacgtgaccgtgac ccatgcgcaggatattctggaaaaaacccataacggcaaactgtgcgatctgaacggcgtgaaa ccgctgattctgaaagattgcagcgtggcgggctggctgctgggcaacccgatgtgcgatgaat ttattaacgtgccggaatggagctatattgtggaaaaagcgaacccggcgaacgatctgtgcta tccgggcaactttaacgattatgaagaactgaaacatctgctgagccgcattaaccattttgaa aaaattcagattattccgaaaagcagctggagcgatcatgaagcgagcctgggcgtgagcgcgg Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 cgtgcccgtatcagggcaacagcagcttttttcgcaacgtggtgtggctgattaaaaaaaacaa cgcgtatccgaccattaaaaaaagctataacaacaccaaccaggaagatctgctggtgctgtgg ggcattcatcatccgaacgatgcggcggaacagacccgcctgtatcagaacccgaccacctata ttagcgtgggcaccagcaccctgaaccagcgcctggtgccgaaaattgcgacccgcagcaaagt gaacggccagagcggccgcatggattttttttggaccattctgaaaccgaacgatgcgattcat tttgaaagcaacggcaactttattgcgccggaatatgcgtataaaattgtgaaaaaaggcgata gcaccattatgaaaagcgaactggaatatggcaactgcaacaccaaatgccagaccccgattgg cgcgattaacagcagcatgccgtttcataacattcatccgctgaccattggcgaatgcccgaaa tatgtgaaaagcaacaaactggtgctggcgaccggcctgcgcaacagcccgcagaacagcccgc agcgcgaacgccgccgcaaacgcggcctgtttggcgcgattgcgggctttattgaaggcggctg gcagggcatggtggatggctggtatggctatcatcatagcaacgaacagggcagcggctatgcg gcggataaagaaagcacccagaaagcgattgatggcgtgaccaacaaagtgaacagcattattg ataaaatgaacacccagtttgaagcggtgggccgcgaatttaacaacctggaacgccgcattga aaacctgaacaaaaaaatggaagatggctttctggatgtgtggacctataacgcggaactgctg gtgctgatggaaaacgaacgcaccctggattttcatgatagcaacgtgaaaaacctgtatgata aagtgcgcctgcagctgaaagataacgcgaaagaactgggcaacggctgctttgaattttatca taaatgcaacaacgaatgcatggaaagcgtgcgcaacggcacctatgattatccgcagtatagc gaagaagcgcgcctgaaacgcgaagaaattagcggcgtgaaactggaaagcattggcatttatc agattctgagcatttatagcaccgtggcgagcagcctggtgctggcgattatgatggcgggcct gagcctgtggatgtgcagcaacggcagcctgcagtgccgcatttgcatt (SEQ ID NO: 35; full- length IAN8 HA nucleotide sequence). The amino acid sequence of a soluble form of the IAN8 immunogenic protein antigen is provided, as follows: IAN8 (soluble HA amino acid sequence): MEKIVLLFAIVSLVKSDQICIGYHANNSTEQVDTIMEKNVTVTHAQDILEKTHNGKLCDLNGVK PLILKDCSVAGWLLGNPMCDEFINVPEWSYIVEKANPANDLCYPGNFNDYEELKHLLSRINHFE KIQIIPKSSWSDHEASLGVSAACPYQGNSSFFRNVVWLIKKNNAYPTIKKSYNNTNQEDLLVLW GIHHPNDAAEQTRLYQNPTTYISVGTSTLNQRLVPKIATRSKVNGQSGRMDFFWTILKPNDAIH FESNGNFIAPEYAYKIVKKGDSTIMKSELEYGNCNTKCQTPIGAINSSMPFHNIHPLTIGECPK YVKSNKLVLATGLRNSPQNSPQRERRRKRGLFGAIAGFIEGGWQGMVDGWYGYHHSNEQGSGYA ADKESTQKAIDGVTNKVNSIIDKMNTQFEAVGREFNNLERRIENLNKKMEDGFLDVWTYNAELL VLMENERTLDFHDSNVKNLYDKVRLQLKDNAKELGNGCFEFYHKCNNECMESVRNGTYDYPQYS EEARLKREEISGV (SEQ ID NO: 36; soluble IAN8 (sIAN8) amino acid sequence). Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 An embodiment of a nucleic acid sequence encoding the soluble form of the IAN8 HA immunogenic protein antigen is provided, as follows: atggaaaaaattgtgctgctgtttgcgattgtgagcctggtgaaaagcgatcagatttgcattg gctatcatgcgaacaacagcaccgaacaggtggataccattatggaaaaaaacgtgaccgtgac ccatgcgcaggatattctggaaaaaacccataacggcaaactgtgcgatctgaacggcgtgaaa ccgctgattctgaaagattgcagcgtggcgggctggctgctgggcaacccgatgtgcgatgaat ttattaacgtgccggaatggagctatattgtggaaaaagcgaacccggcgaacgatctgtgcta tccgggcaactttaacgattatgaagaactgaaacatctgctgagccgcattaaccattttgaa aaaattcagattattccgaaaagcagctggagcgatcatgaagcgagcctgggcgtgagcgcgg cgtgcccgtatcagggcaacagcagcttttttcgcaacgtggtgtggctgattaaaaaaaacaa cgcgtatccgaccattaaaaaaagctataacaacaccaaccaggaagatctgctggtgctgtgg ggcattcatcatccgaacgatgcggcggaacagacccgcctgtatcagaacccgaccacctata ttagcgtgggcaccagcaccctgaaccagcgcctggtgccgaaaattgcgacccgcagcaaagt gaacggccagagcggccgcatggattttttttggaccattctgaaaccgaacgatgcgattcat tttgaaagcaacggcaactttattgcgccggaatatgcgtataaaattgtgaaaaaaggcgata gcaccattatgaaaagcgaactggaatatggcaactgcaacaccaaatgccagaccccgattgg cgcgattaacagcagcatgccgtttcataacattcatccgctgaccattggcgaatgcccgaaa tatgtgaaaagcaacaaactggtgctggcgaccggcctgcgcaacagcccgcagaacagcccgc agcgcgaacgccgccgcaaacgcggcctgtttggcgcgattgcgggctttattgaaggcggctg gcagggcatggtggatggctggtatggctatcatcatagcaacgaacagggcagcggctatgcg gcggataaagaaagcacccagaaagcgattgatggcgtgaccaacaaagtgaacagcattattg ataaaatgaacacccagtttgaagcggtgggccgcgaatttaacaacctggaacgccgcattga aaacctgaacaaaaaaatggaagatggctttctggatgtgtggacctataacgcggaactgctg gtgctgatggaaaacgaacgcaccctggattttcatgatagcaacgtgaaaaacctgtatgata aagtgcgcctgcagctgaaagataacgcgaaagaactgggcaacggctgctttgaattttatca taaatgcaacaacgaatgcatggaaagcgtgcgcaacggcacctatgattatccgcagtatagc gaagaagcgcgcctgaaacgcgaagaaattagcggcgtg(SEQ ID NO: 37; soluble IAN8 (sIAN8) nucleic acid sequence). The following amino acid sequence, or a fragment thereof, optionally including a His tag (e.g., six consecutive histidine amino acids), may be added to or included at the carboxy (COOH) terminus of the IAN8 HA soluble protein: IGSGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGLNDIFEAQKIEWHEGHHHHHH (SEQ ID NO: 38). Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 The above-noted amino acid sequence, including a His tag (e.g., six consecutive histidine amino acids), that may be added to or included at the carboxy (COOH) terminus of the IAN8 HA soluble protein may be encoded by the following nucleic acid sequence: tgcattggcagcggctatattccggaagcgccgcgcgatggccaggcgtatgtgcgcaaagatg gcgaatgggtgctgctgagcacctttctgggcagcggcctgaacgatatttttgaagcgcagaa aattgaatggcatgaaggccatcatcatcatcatcat (SEQ ID NO: 39). In an embodiment, an HA immunogenic protein antigen termed “NG3” is used in the octavalent / pentavalent immunogenic / vaccine composition and formulation described herein. NG3 is an H3 HA protein, which comprises or consists of the following full-length amino acid sequence, or a fragment thereof: NG3 (full length amino acid sequence, where the stalk and transmembrane domains are underlined): MKTIIALSYILCLVFAQKIPGNDNSTATLCLGHHAVPNGTIVKTITNDRIEVTNATELVQNSSI GEICDSPHQILDGGNCTLIDALLGDPQCDGFQNKKWDLFVERSRAYSNCYPYDVPDYASLRSLV ASSGTLEFKNESFNWTGVTQNGTSSACIRGSSSSFFSRLNWLTHLNYTYPALNVTMPNKEQFDK LYIWGVHHPGTDKDQIFLYAQSSGRITVSTKRSQQAVIPNIGSRPRIRDIPSRISIYWTIVKPG DILLINSTGNLIAPRGYFKIRSGKSSIMRSDAPIGKCKSECITPNGSIPNDKPFQNVNRITYGA CPRYVKQSTLKLATGMRNVPEKQTRGIFGAIAGFIENGWEGMVDGWYGFRHQNSEGRGQAADLK STQAAIDQINGKLNRLIGKTNEKFHQIEKEFSEVEGRIQDLEKYVEDTKIDLWSYNAELLVALE NQHTIDLTDSEMNKLFEKTKKQLRENAEDMGNGCFKIYHKCDNACIGSIRNGTYDHNVYRDEAL NNRFQIKGVELKSGYKDWILWISFAISCFLLCVALLGFIMWACQKGNIRCNICI (SEQ ID NO: 40; NG3 HA full length amino acid sequence). In embodiments, stalk and transmembrane domains of NG3 are removed. An embodiment of a nucleic acid sequence encoding the full-length NG3 HA immunogenic protein antigen is provided as follows: NG3 (full length nucleotide sequence, where nucleotides encoding the stalk and transmembrane domains are underlined): atgaaaaccattattgcgctgagctatattctgtgcctggtgtttgcgcagaaaattccgggca acgataacagcaccgcgaccctgtgcctgggccatcatgcggtgccgaacggcaccattgtgaa aaccattaccaacgatcgcattgaagtgaccaacgcgaccgaactggtgcagaacagcagcatt ggcgaaatttgcgatagcccgcatcagattctggatggcggcaactgcaccctgattgatgcgc tgctgggcgatccgcagtgcgatggctttcagaacaaaaaatgggatctgtttgtggaacgcag ccgcgcgtatagcaactgctatccgtatgatgtgccggattatgcgagcctgcgcagcctggtg gcgagcagcggcaccctggaatttaaaaacgaaagctttaactggaccggcgtgacccagaacg Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 gcaccagcagcgcgtgcattcgcggcagcagcagcagcttttttagccgcctgaactggctgac ccatctgaactatacctatccggcgctgaacgtgaccatgccgaacaaagaacagtttgataaa ctgtatatttggggcgtgcatcatccgggcaccgataaagatcagatttttctgtatgcgcaga gcagcggccgcattaccgtgagcaccaaacgcagccagcaggcggtgattccgaacattggcag ccgcccgcgcattcgcgatattccgagccgcattagcatttattggaccattgtgaaaccgggc gatattctgctgattaacagcaccggcaacctgattgcgccgcgcggctattttaaaattcgca gcggcaaaagcagcattatgcgcagcgatgcgccgattggcaaatgcaaaagcgaatgcattac cccgaacggcagcattccgaacgataaaccgtttcagaacgtgaaccgcattacctatggcgcg tgcccgcgctatgtgaaacagagcaccctgaaactggcgaccggcatgcgcaacgtgccggaaa aacagacccgcggcatttttggcgcgattgcgggctttattgaaaacggctgggaaggcatggt ggatggctggtatggctttcgccatcagaacagcgaaggccgcggccaggcggcggatctgaaa agcacccaggcggcgattgatcagattaacggcaaactgaaccgcctgattggcaaaaccaacg aaaaatttcatcagattgaaaaagaatttagcgaagtggaaggccgcattcaggatctggaaaa atatgtggaagataccaaaattgatctgtggagctataacgcggaactgctggtggcgctggaa aaccagcataccattgatctgaccgatagcgaaatgaacaaactgtttgaaaaaaccaaaaaac agctgcgcgaaaacgcggaagatatgggcaacggctgctttaaaatttatcataaatgcgataa cgcgtgcattggcagcattcgcaacggcacctatgatcataacgtgtatcgcgatgaagcgctg aacaaccgctttcagattaaaggcgtggaactgaaaagcggctataaagattggattctgtgga ttagctttgcgattagctgctttctgctgtgcgtggcgctgctgggctttattatgtgggcgtg ccagaaaggcaacattcgctgcaacatttgcatt (SEQ ID NO: 41; full-length NG3 HA nucleotide sequence). The amino acid sequence of a soluble form of the NG3 immunogenic protein antigen is provided, as follows: NG3 (soluble HA amino acid sequence): MKTIIALSYILCLVFAQKIPGNDNSTATLCLGHHAVPNGTIVKTITNDRIEVTNATELVQNSSI GEICDSPHQILDGGNCTLIDALLGDPQCDGFQNKKWDLFVERSRAYSNCYPYDVPDYASLRSLV ASSGTLEFKNESFNWTGVTQNGTSSACIRGSSSSFFSRLNWLTHLNYTYPALNVTMPNKEQFDK LYIWGVHHPGTDKDQIFLYAQSSGRITVSTKRSQQAVIPNIGSRPRIRDIPSRISIYWTIVKPG DILLINSTGNLIAPRGYFKIRSGKSSIMRSDAPIGKCKSECITPNGSIPNDKPFQNVNRITYGA CPRYVKQSTLKLATGMRNVPEKQTRGIFGAIAGFIENGWEGMVDGWYGFRHQNSEGRGQAADLK STQAAIDQINGKLNRLIGKTNEKFHQIEKEFSEVEGRIQDLEKYVEDTKIDLWSYNAELLVALE NQHTIDLTDSEMNKLFEKTKKQLRENAEDMGNGCFKIYHKCDNACIGSIRNGTYDHNVYRDEAL NNRFQIKGVELKSGYKD (SEQ ID NO: 42; soluble NG3 (sNG3) amino acid sequence). Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 An embodiment of a nucleic acid sequence encoding the soluble form of the NG3 HA immunogenic protein antigen is provided, as follows: aagcttatgaaaacaatcatcgctctgtcctatattctgtgcctcgtgttcgctcagaagatcc ccggcaatgacaacagcaccgctacactgtgtctcggccatcacgccgtgcccaatggcaccat cgtcaagaccatcaccaacgataggatcgaggtgaccaacgccaccgagctggtgcagaacagc agcattggcgaaatctgtgactcccctcatcagatcctcgacggcggcaactgtacactgattg acgctctgctcggagacccccaatgcgatggcttccagaacaagaagtgggatctgttcgtgga aaggtccagagcctacagcaactgctatccctacgacgtgcccgactacgcttctctgagatct ctggtcgccagcagcggaacactcgagttcaagaacgagtccttcaactggaccggagtgaccc agaacggcacaagctccgcttgcattaggggaagctccagcagcttcttctctagactgaattg gctgacccacctcaactacacctatcccgctctcaacgtgaccatgcccaacaaggagcagttc gacaaactgtacatctggggcgtccaccatcccggcaccgacaaggaccagatctttctgtatg cccagtcctccggcagaatcacagtgagcaccaagaggtcccaacaagccgtcatccccaacat cggctccagacctaggattagagacatcccttctagaatcagcatttactggaccatcgtgaag cccggcgatattctgctcatcaacagcaccggcaacctcatcgcccctaggggatacttcaaga ttagaagcggcaaaagctccatcatgaggagcgacgcccctattggcaaatgcaagagcgagtg catcacccccaatggcagcatccccaacgacaaacccttccagaacgtcaacagaatcacatac ggcgcttgccctagatatgtcaaacagtccacactgaagctcgccaccggcatgaggaatgtcc ccgagaagcagacaagaggaatcttcggcgctattgccggcttcatcgaaaacggctgggaagg catggtggacggatggtacggcttcagacaccagaacagcgagggaagaggacaagccgctgat ctgaaaagcacacaagccgccatcgaccagatcaacggaaagctcaataggctcatcggcaaga caaacgaaaagtttcatcaaattgaaaaggagttctccgaggtcgagggaagaatccaagatct ggagaagtacgtggaggacaccaaaatcgatctgtggtcctacaacgctgaactgctggtggct ctggaaaaccagcacacaatcgatctcaccgatagcgagatgaacaagctgtttgaaaaaacaa aaaaacaactgagagagaatgccgaggatatgggcaacggctgcttcaagatctaccacaagtg tgacaatgcttgcatcggcagcatcagaaatggaacctatgaccataatgtgtatagagacgaa gctctgaacaataggttccagatcaagggagtggagctgaaatccggctacaaggac (SEQ ID NO: 43; soluble Y4 (sNG3) nucleic acid sequence). The following amino acid sequence, or a fragment thereof, optionally including a His tag (e.g., six consecutive histidine amino acids), may be added to or included at the carboxy (COOH) terminus of the NG3 HA soluble protein: GSGYIPEAPRDGQAYVRKDGEWVLLSTFLGLNDIFEAQKIEWHEGHHHHHHGS (SEQ ID NO: 27). Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 The above-noted amino acid sequence, including a His tag (e.g., six consecutive histidine amino acids), that may be added to or included at the carboxy (COOH) terminus of the NG3 HA soluble protein may be encoded by the following nucleic acid sequence: ggaagcggctacatccccgaggcccctagagatggacaagcctacgtcagaaaggacggcgagt gggtgctgctgtccacctttctcggactgaacgacatctttgaggcccagaaaatcgagtggca cgaaggacatcaccaccatcaccatggatcc (SEQ ID NO: 44). In an embodiment, an HA immunogenic protein antigen termed “Q6” is used in the octavalent / pentavalent immunogenic / vaccine composition and formulation described herein. Q6 is an H7 HA protein, which comprises or consists of the following full length amino acid sequence, or a fragment thereof: Q6 (full length amino acid sequence, where the stalk and transmembrane domains are underlined): MNTQILALVACMLIGVKGDKICLGHHAVSNGTKVNTLTERGVEVVNATETVERTNIPRICSKGK RTVDLGQCGLLGTITGPPQCDQFLEFSADLIIERREGTDVCYPGKFVNEEALRQILRESGGIDK ESMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKKPALIIWGIH HSGSTTEQTKLYGSGNKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFHWLMLNPNDTVTFSF NGAFIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQ ESLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQGEGTAADYKSTQSAI DQITGKLNRLIEKTNQQFELIDNEFNEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTID LADSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHSKYREEAMQNRIQI DPVKLSSGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI (SEQ ID NO: 45; Q6 HA full length amino acid sequence). In embodiments, the stalk and transmembrane domains of Q6 are removed. An embodiment of a nucleic acid sequence encoding the full-length Q6 HA immunogenic protein antigen is provided as follows: Q6 (full length nucleotide sequence, where nucleotides encoding the stalk and transmembrane domains are underlined): aagcttatgaacacacagatcctggccctggtggcctgcatgctgatcggcgtgaagggcgaca agatctgcctgggccaccacgccgtgagcaacggcaccaaggtgaacaccctgaccgagagagg cgtggaggtggtgaacgccaccgagaccgtggagagaaccaacatccctagaatctgcagcaag ggcaagagaaccgtggacctggggcagtgcggcctgctgggcaccatcaccggcccccctcagt gcgatcagttcctggagttcagcgccgacctgatcatcgagagaagagagggcaccgacgtgtg ctaccccggcaagttcgtgaacgaggaggccctgagacagatcctgagagagagcggcggcatc gacaaggagagcatgggcttcacctacagcggcatcagaaccaacggcgccacaagcgcctgca Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 gaagaagcggcagcagcttctacgccgagatgaagtggctgctgagcaacaccgacaacgccgc cttccctcagatgaccaagagctacaagaacacaagaaagaagcccgccctgatcatctggggc atccaccacagcggcagcaccaccgagcagaccaagctgtacggcagcggcaacaagctgatca ccgtgggcagcagcaactatcagcagagcttcgtgcctagccccggcgctagaccccaagtgaa cgggcagagcggcagaatcgacttccactggctgatgctgaaccccaacgacaccgtgaccttc agcttcaacggcgccttcatcgcccccgacagagctagcttcctgagaggcaagagcatgggca ttcagagcggcgtgcaagtggacgccaactgcgagggcgactgctaccacagcggcggcaccat catcagcaacctgccctttcagaacatcaacagcagagccgtgggcaagtgccctagatacgtg aagcaagagagcctgctgctggccaccggcatgaagaacgtgcccgagatccccaagggcagag gcctgttcggcgccatcgccggcttcatcgagaacggctgggagggcctgatcgacggctggta cggcttcagacatcagaacgcccaaggcgagggcaccgccgccgactacaagagcacacagagc gccatcgatcagatcaccggcaagctgaacagactgatcgagaagaccaatcagcagttcgagc tgatcgacaacgagttcaacgaggtggagaagcagatcggcaacgtgatcaactggacaagaga cagcatgaccgaggtgtggagctacaacgccgagctgctggtggccatggagaatcagcacacc atcgacctggccgacagcgagatgaacaagctgtacgagagagtgaagagacagctgagagaga acgccgaggaggacggcaccggctgcttcgagatcttccacaagtgcgacgacgactgcatggc tagcatcagaaacaacacctacgaccacagcaagtacagagaggaggccatgcagaacagaatt cagatcgaccccgtgaagctgagcagcggctacaaggacgtgatcctgtggttcagcttcggcg ctagctgcttcatcctgctggccatcgccatgggcctggtgttcatctgcgtgaagaacggcaa catgagatgcaccatctgcatctgatgaggatcc (SEQ ID NO: 46; full-length Q6 HA nucleotide sequence). The amino acid sequence of a soluble form of the Q6 HA immunogenic protein antigen is provided, as follows: Q6 (soluble HA amino acid sequence): MNTQILALVACMLIGVKGDKICLGHHAVSNGTKVNTLTERGVEVVNATETVERTNIPRICSKGK RTVDLGQCGLLGTITGPPQCDQFLEFSADLIIERREGTDVCYPGKFVNEEALRQILRESGGIDK ESMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKKPALIIWGIH HSGSTTEQTKLYGSGNKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFHWLMLNPNDTVTFSF NGAFIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQ ESLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQGEGTAADYKSTQSAI DQITGKLNRLIEKTNQQFELIDNEFNEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTID LADSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHSKYREEAMQNRIQI DPV (SEQ ID NO: 47; soluble Q6 (sQ6) amino acid sequence). Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 An embodiment of a nucleic acid sequence encoding the soluble form of the Q6 HA immunogenic protein antigen is provided, as follows: aagcttatgaacacacagatcctggccctggtggcctgcatgctgatcggcgtgaagggcgaca agatctgcctgggccaccacgccgtgagcaacggcaccaaggtgaacaccctgaccgagagagg cgtggaggtggtgaacgccaccgagaccgtggagagaaccaacatccctagaatctgcagcaag ggcaagagaaccgtggacctggggcagtgcggcctgctgggcaccatcaccggcccccctcagt gcgatcagttcctggagttcagcgccgacctgatcatcgagagaagagagggcaccgacgtgtg ctaccccggcaagttcgtgaacgaggaggccctgagacagatcctgagagagagcggcggcatc gacaaggagagcatgggcttcacctacagcggcatcagaaccaacggcgccacaagcgcctgca gaagaagcggcagcagcttctacgccgagatgaagtggctgctgagcaacaccgacaacgccgc cttccctcagatgaccaagagctacaagaacacaagaaagaagcccgccctgatcatctggggc atccaccacagcggcagcaccaccgagcagaccaagctgtacggcagcggcaacaagctgatca ccgtgggcagcagcaactatcagcagagcttcgtgcctagccccggcgctagaccccaagtgaa cgggcagagcggcagaatcgacttccactggctgatgctgaaccccaacgacaccgtgaccttc agcttcaacggcgccttcatcgcccccgacagagctagcttcctgagaggcaagagcatgggca ttcagagcggcgtgcaagtggacgccaactgcgagggcgactgctaccacagcggcggcaccat catcagcaacctgccctttcagaacatcaacagcagagccgtgggcaagtgccctagatacgtg aagcaagagagcctgctgctggccaccggcatgaagaacgtgcccgagatccccaagggcagag gcctgttcggcgccatcgccggcttcatcgagaacggctgggagggcctgatcgacggctggta cggcttcagacatcagaacgcccaaggcgagggcaccgccgccgactacaagagcacacagagc gccatcgatcagatcaccggcaagctgaacagactgatcgagaagaccaatcagcagttcgagc tgatcgacaacgagttcaacgaggtggagaagcagatcggcaacgtgatcaactggacaagaga cagcatgaccgaggtgtggagctacaacgccgagctgctggtggccatggagaatcagcacacc atcgacctggccgacagcgagatgaacaagctgtacgagagagtgaagagacagctgagagaga acgccgaggaggacggcaccggctgcttcgagatcttccacaagtgcgacgacgactgcatggc tagcatcagaaacaacacctacgaccacagcaagtacagagaggaggccatgcagaacagaatt cagatcgaccccgtg(SEQ ID NO: 48; soluble Q6 (sQ6) nucleic acid sequence). The following amino acid sequence, or a fragment thereof, optionally including a His tag (e.g., six consecutive histidine amino acids), may be added to or included at the carboxy (COOH) terminus of the Q6 HA soluble protein: GYIPEAPRDGQAYVRKDGEWVLLSTFLGSGLNDIFEAQKIEWHEGHHHHHH (SEQ ID NO: 49). The above-noted amino acid sequence, including a His tag (e.g., six consecutive histidine amino acids), that may be added to or included at the carboxy (COOH) terminus of the Q6 HA soluble protein may be encoded by the following nucleic acid sequence: Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 ggatacattcccgaagcccctagagatggccaggcttacgtgagaaaggatggcgagtgggtgc tgctgtccacctttctgggctccggactgaacgatatcttcgaggcccagaagatcgaatggca cgagggccatcaccaccaccatcattgatgaggatcc (SEQ ID NO: 50). In an embodiment, an HA immunogenic protein antigen termed “Y4” is used in the octavalent / pentavalent immunogenic / vaccine composition and formulation described herein. Y4 is an H1 HA protein, which comprises or consists of the following full length amino acid sequence, or a fragment thereof: Y4 (full length amino acid sequence, where the stalk and transmembrane domains are underlined): MKAILVVLLYTFTTANADTLCIGYHANNSTDTVDTVLEKNVTVTHSVNLLEDKHNGKLCKLRGV APLHLGKCNIAGWILGNPECESLSTARSWSYIVETSNSDNGTCYPGDFINYEELREQLSSVSSF ERFEIFPKTSSWPNHDSNKGVTAACPHAGAKSFYKNLIWLVKKGNSYPKLNQTYINDKGKEVLV LWGIHHPSTTADQQSLYQNADAYVFVGTSRYSKKFKPEIATRPKVRDQEGRMNYYWTLVEPGDK ITFEATGNLVVPRYAFTMERNAGSGIIISDTPVHDCNTTCQTPEGAINTSLPFQNVHPITIGKC PKYVKSTKLRLATGLRNVPSIQSRGLFGAIAGFIEGGWTGMVDGWYGYHHQNEQGSGYAADLKS TQNAIDKITNKVNSVIEKMNTQFTAVGKEFNHLEKRIENLNKKVDDGFLDIWTYNAELLVLLEN ERTLDYHDSNVKNLYEKVRNQLKNNAKEIGNGCFEFYHKCDNTCMESVKNGTYDYPKYSEEAKL NREKIDGVKLESTRIYQILAIYSTVASSLVLVVSLGAISFWMCSNGSLQCRICI (SEQ ID NO: 51; Y4 HA full length amino acid sequence). In embodiments, the stalk and transmembrane domains of Y4 are removed. An embodiment of a nucleic acid sequence encoding the full-length Y4 HA immunogenic protein antigen is provided as follows: Y4 (full length nucleotide sequence, where nucleotides encoding the stalk and transmembrane domains are underlined): aagcttatgaaagccattctggtggtgctcctctacacctttaccaccgctaacgccgacaccc tctgcatcggctaccacgccaacaactccaccgatacagtggacacagtgctggagaagaacgt cacagtcacccatagcgtgaatctgctggaggacaaacacaacggcaagctgtgtaagctgagg ggagtggcccctctgcatctgggcaagtgtaacatcgccggctggattctgggcaaccccgagt gtgaaagcctctccaccgccagaagctggagctatatcgtcgagacctccaacagcgacaacgg aacatgctaccccggcgacttcatcaactacgaggagctgagagagcaactctcctccgtcagc tcctttgagaggttcgagatctttcccaagaccagcagctggcccaatcatgacagcaacaagg gcgtgacagctgcttgccctcacgccggagccaagagcttttacaagaatctcatctggctcgt gaagaaaggcaacagctaccccaagctcaatcagacctacatcaacgataagggcaaggaggtg ctggtgctgtggggaattcaccatccttccacaaccgccgatcaacagagcctctatcagaacg Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 ctgacgcctacgtgttcgtgggaacctctagatactccaagaagttcaagcccgagatcgctac aaggcccaaggtgagggaccaagagggcagaatgaactactactggacactcgtggagcccggc gataagatcacattcgaggctaccggcaacctcgtcgtgcctagatatgcctttacaatggaga ggaatgccggcagcggaatcattatcagcgacacacccgtgcacgattgcaacaccacatgtca gacccccgagggcgctattaatacctctctgccttttcagaacgtgcaccccatcacaatcggc aagtgccctaagtacgtgaagagcaccaagctgagactggccaccggactgagaaacgtcccct ccattcagtccagaggactgtttggcgctattgccggattcatcgaaggaggatggaccggcat ggtggacggctggtacggctaccatcaccagaatgagcaaggcagcggctacgccgccgacctc aagtccacccagaatgccatcgacaaaatcaccaataaggtgaactccgtcatcgagaagatga acacccagttcacagccgtcggaaaagagtttaaccatctggagaaaagaattgagaatctgaa caagaaggtcgacgacggctttctggacatctggacctacaatgctgagctgctggtgctgctc gagaacgaaagaaccctcgactaccacgacagcaacgtcaagaatctgtatgagaaagtgagaa accagctgaagaacaacgccaaggagatcggaaacggctgcttcgagttctaccataagtgtga caacacatgcatggagagcgtgaagaacggaacatacgactaccctaaatatagcgaggaggcc aagctcaacagagagaagattgacggcgtgaagctcgagagcacaagaatctaccagattctgg ctatttacagcaccgtggcctcctctctggtgctggtggtcagcctcggagccatctccttttg gatgtgcagcaatggctctctgcaatgcagaatctgcatcggatcc (SEQ ID NO: 52; full- length Y4 HA nucleotide sequence). The amino acid sequence of a soluble form of the Y4 HA immunogenic protein antigen is provided, as follows: Y4 (soluble HA amino acid sequence): MKAILVVLLYTFTTANADTLCIGYHANNSTDTVDTVLEKNVTVTHSVNLLEDKHNGKLCKLRGV APLHLGKCNIAGWILGNPECESLSTARSWSYIVETSNSDNGTCYPGDFINYEELREQLSSVSSF ERFEIFPKTSSWPNHDSNKGVTAACPHAGAKSFYKNLIWLVKKGNSYPKLNQTYINDKGKEVLV LWGIHHPSTTADQQSLYQNADAYVFVGTSRYSKKFKPEIATRPKVRDQEGRMNYYWTLVEPGDK ITFEATGNLVVPRYAFTMERNAGSGIIISDTPVHDCNTTCQTPEGAINTSLPFQNVHPITIGKC PKYVKSTKLRLATGLRNVPSIQSRGLFGAIAGFIEGGWTGMVDGWYGYHHQNEQGSGYAADLKS TQNAIDKITNKVNSVIEKMNTQFTAVGKEFNHLEKRIENLNKKVDDGFLDIWTYNAELLVLLEN ERTLDYHDSNVKNLYEKVRNQLKNNAKEIGNGCFEFYHKCDNTCMESVKNGTYDYPKYSEEAKL NREKIDGV (SEQ ID NO: 53; soluble Y4 (sY4) amino acid sequence). An embodiment of a nucleic acid sequence encoding the soluble form of the Y4 HA immunogenic protein antigen is provided, as follows: aagcttatgaaggccatcctcgtcgtgctgctgtacacattcacaaccgctaatgccgacacac tgtgcattggctaccacgccaataactccaccgacaccgtggacacagtgctggagaagaatgt Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 gaccgtgacccacagcgtcaatctgctggaagacaagcacaatggcaagctgtgcaagctgagg ggagtggcccccctccatctgggaaaatgcaacatcgccggctggattctgggcaaccccgaat gtgagtctctgtccaccgctagaagctggtcctacatcgtcgagacatccaacagcgacaatgg cacatgctaccccggcgactttattaattacgaagaactcagagagcaactgagcagcgtgagc tccttcgagaggttcgagatcttccctaagacctccagctggcctaaccatgacagcaataagg gagtgaccgctgcttgtccccacgccggcgctaagagcttctacaaaaatctgatttggctggt caagaagggcaactcctaccccaaactgaatcagacatatatcaatgataagggcaaagaggtg ctggtgctctggggcattcaccaccccagcaccacagccgatcagcagagcctctatcagaacg ccgacgcctatgtgttcgtgggcacctctagatactccaagaagttcaagcccgagatcgccac aagacctaaagtgagagaccaagagggaagaatgaactactactggacactggtcgagcccggc gataagatcaccttcgaggccaccggaaatctcgtcgtgcctaggtacgccttcaccatggaga ggaatgctggcagcggcatcattatctccgacacccccgtccacgattgcaacacaacatgcca gacccccgagggcgccatcaatacctctctgcctttccagaacgtccatcctatcaccatcgga aagtgccccaagtacgtcaagtccacaaagctgagactggccaccggactgaggaatgtgccca gcatccaaagcagaggactgtttggcgccattgccggattcatcgaaggaggatggaccggcat ggtggatggctggtacggctaccatcaccagaacgagcaaggctccggctacgccgccgatctg aagtccacccagaacgccatcgacaagatcaccaataaggtgaatagcgtgattgagaagatga atacccagtttaccgccgtgggcaaagagtttaaccacctcgagaagaggatcgagaatctgaa caagaaggtggacgatggcttcctcgacatctggacctacaacgccgagctgctcgtgctgctg gagaacgagagaacactggattaccacgactccaacgtgaagaacctctatgagaaggtgagaa atcagctgaagaataatgccaaggagattggcaacggctgcttcgagttctaccacaagtgcga caatacatgcatggagagcgtgaaaaacggcacctatgactatcccaagtacagcgaggaggcc aagctgaatagagagaagatcgacggagtg(SEQ ID NO: 54; soluble Y4 (sY4) nucleic acid sequence). The following amino acid sequence, or a fragment thereof, optionally including a His tag (e.g., six consecutive histidine amino acids), may be added to or included at the carboxy (COOH) terminus of the Y4 HA soluble protein: GTGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGLNDIFEAQKIEWHEGHHHHHH (SEQ ID NO: 23). The above-noted amino acid sequence, including a His tag (e.g., six consecutive histidine amino acids), that may be added to or included at the carboxy (COOH) terminus of the Y4 HA soluble protein may be encoded by the following nucleic acid sequence: Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 ggcaccggctacatccccgaagctcccagagatggacaagcctacgtgaggaaagacggcgagt gggtgctgctgtccacctttctgggaagcggactgaacgacatcttcgaggctcagaagatcga gtggcacgagggacatcaccatcaccatcattgatgaggatcc (SEQ ID NO: 55). In an embodiment, an HA immunogenic protein antigen termed “Z1” is used in the octavalent / pentavalent immunogenic / vaccine composition and formulation described herein. Z1 is an H2 HA protein, which comprises or consists of the following full length amino acid sequence, or a fragment thereof: Z1 (full length amino acid sequence, where the stalk and transmembrane domains are underlined): MAIIYLILLFTAVRGDQICIGYHANNSTEKVDTILERNVTVTHAKDILEKTHNGKLCKLNGIPP LELGDCSIAGWLLGNPECDRLLSVPEWSYIMEKENPRNGLCYPGSFNDYEELKHLLSSVTHFEK VKILPKDRWTQHTTTGGSRACAVSGNPSFFRNMVWLTKKGSNYPVAKGSYNNTSGEQMLIIWGV HHPNDEAEQRTLYQNVGTYVSVGTSTLNKRSIPEIATRPKVNGQGGRMEFSWTLLDMWDTINFE STGNLIAPEYGFKISKRGSSGIMKTEGTLENCETKCQTPLGAINTTLPFHNIHPLTIGECPKYV KSERLVLATGLRNVPQIESRGLFGAIAGFIEGGWQGMVDGWYGYHHSNDQGSGYAADKESTQKA IDGITNKVNSVIEKMNTQFEAVGKEFNNLERRLENLNKKMEDGFLDVWTYNAELLVLMENERTL DFHDSNVKNLYDKVRMQLRDNAKELGNGCFEFYHKCDDECMNSVKNGTYDYPKYEEESKLNRNE IKGVKLSNMGVYQILAIYATVAGSLSLAIMIAGISFWMCSNGSLQCRICI (SEQ ID NO: 56; Z1 HA full length amino acid sequence). In embodiments, the stalk and transmembrane domains of Z1 are removed. An embodiment of a nucleic acid sequence encoding the full-length Z1 HA immunogenic protein antigen is provided as follows: Z1 (full length nucleotide sequence, where nucleotides encoding the stalk and transmembrane domains are underlined): aagcttatggccatcatctatttaattctcctcttcaccgccgtgaggggagatcagatctgca ttggctaccacgccaataactccacagagaaggtggacaccattctcgagaggaatgtgacagt gacccatgctaaggacattttagagaagacccataacggcaagctgtgcaagctgaacggaatt ccccctctcgagctgggcgattgctccatcgctggctggctgctcggaaaccccgagtgtgaca gactgctctccgtgcccgagtggagctatatcatggagaaggagaatcctagaaatggcctctg ttatcccggcagcttcaatgactacgaggagctcaagcatctgctgtccagcgtgacacacttc gagaaggtcaagattttacccaaggatcgttggacccagcacacaaccactggtggctctcgtg cttgtgctgtcagcggcaaccctagcttctttcgtaacatggtctggctgaccaaaaagggctc caactaccccgttgctaagggaagctacaacaacacctccggcgagcagatgctgatcatctgg ggagtgcaccaccccaacgacgaggccgagcagaggactttataccagaacgtgggaacctacg Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 tgagcgtgggcaccagcaccctcaacaagaggagcatccccgagatcgccactcgtcctaaagt caacggccaaggtggaaggatggagttcagctggactttactcgacatgtgggacacaatcaac ttcgagagcaccggaaatttaatcgcccccgagtacggcttcaagattagcaagaggggaagca gcggaatcatgaaaaccgagggaacactcgaaaactgcgagaccaaatgccagacccctttagg cgctatcaataccactttaccctttcacaacatccaccctctcacaatcggcgagtgtcccaag tacgtgaagtccgagaggctggttttagccaccggactgagaaacgtgcctcagatcgaatctc gtggtttattcggcgccatcgctggctttatcgagggcggctggcaaggtatggtggacggctg gtacggctaccaccatagcaacgaccaaggtagcggctacgctgccgacaaggagtccacccag aaggccatcgatggcatcaccaataaggtgaatagcgtcatcgagaagatgaacacccagttcg aggccgtgggcaaggagttcaacaatttagagagaaggctcgaaaatctcaacaagaaaatgga ggacggctttttagacgtgtggacctataatgccgagctgctggttttaatggagaatgagagg accctcgacttccacgacagcaacgtgaagaacctctacgacaaggtgaggatgcaactgagag acaacgccaaggagctcggcaacggatgtttcgagttctatcacaagtgtgacgatgaatgtat gaacagcgtcaaaaacggcacctacgactaccccaagtacgaggaagaatccaagctgaataga aatgagatcaagggagtcaagctcagcaacatgggagtgtatcagattttagccatctacgcca ccgtggctggctctttatctttagccatcatgatcgccggaatcagcttctggatgtgttccaa tggctctttacagtgtcgtatctgcatttgaggatcc (SEQ ID NO: 57; full-length Z1 HA nucleotide sequence). The amino acid sequence of a soluble form of the Z1 HA immunogenic protein antigen is provided, as follows: Z1 (soluble HA amino acid sequence): MAIIYLILLFTAVRGDQICIGYHANNSTEKVDTILERNVTVTHAKDILEKTHNGKLCKLNGIPP LELGDCSIAGWLLGNPECDRLLSVPEWSYIMEKENPRNGLCYPGSFNDYEELKHLLSSVTHFEK VKILPKDRWTQHTTTGGSRACAVSGNPSFFRNMVWLTKKGSNYPVAKGSYNNTSGEQMLIIWGV HHPNDEAEQRTLYQNVGTYVSVGTSTLNKRSIPEIATRPKVNGQGGRMEFSWTLLDMWDTINFE STGNLIAPEYGFKISKRGSSGIMKTEGTLENCETKCQTPLGAINTTLPFHNIHPLTIGECPKYV KSERLVLATGLRNVPQIESRGLFGAIAGFIEGGWQGMVDGWYGYHHSNDQGSGYAADKESTQKA IDGITNKVNSVIEKMNTQFEAVGKEFNNLERRLENLNKKMEDGFLDVWTYNAELLVLMENERTL DFHDSNVKNLYDKVRMQLRDNAKELGNGCFEFYHKCDDECMNSVKNGTYDYPKYEEESKLNRNE IKGVKLSNMGVYQ (SEQ ID NO: 58; soluble Z1 (sZ1) amino acid sequence). An embodiment of a nucleic acid sequence encoding the soluble form of the Z1 HA immunogenic protein antigen is provided, as follows: Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 Z1 (soluble HA nucleotide sequence): aagcttatggccatcatctacctcattctgctgtttaccgccgtgaggggcgaccagatctgta tcggctaccacgccaacaacagcaccgagaaggtggacaccattctcgagaggaacgtcaccgt gacccacgccaaagacattctggagaagacccacaatggcaagctctgcaaactgaacggcatc ccccctctggagctcggcgattgttccattgctggctggctgctcggcaatcccgaatgtgaca gactgctgtccgtccccgagtggagctatatcatggagaaggagaaccccagaaacggactgtg ttatcccggcagcttcaacgattacgaggagctgaagcatctgctgagcagcgtcacccacttc gagaaggtgaagattctgcctaaggatagatggacccagcataccaccaccggcggcagcagag cttgcgctgtgagcggaaaccctagcttctttagaaacatggtctggctgaccaagaagggctc caactaccccgtcgctaagggcagctacaacaacacaagcggcgagcaaatgctgatcatctgg ggcgtgcatcaccccaacgacgaggctgaacagagaaccctctatcagaacgtgggcacatatg tctccgtcggcacctccacactgaacaagagaagcatccccgagatcgccacaagacccaaggt gaacggacaaggcggcagaatggagttcagctggacactgctggacatgtgggataccatcaac ttcgagtccaccggaaatctgatcgcccccgaatatggcttcaagatttccaagaggggcagct ccggcatcatgaaaaccgagggcacactggagaactgcgagaccaagtgtcagacacctctggg cgccatcaacaccacactgcctttccacaacatccaccctctgacaatcggcgaatgccccaag tacgtgaaatccgagagactcgtcctcgccaccggcctcagaaatgtgccccagattgagagca gaggactgtttggcgctatcgccggctttattgaaggcggatggcaaggcatggtggacggatg gtacggctatcaccacagcaacgaccaaggcagcggctacgccgctgataaggagtccacacag aaggccatcgacggcatcaccaacaaagtcaacagcgtgatcgagaagatgaacacccagttcg aggccgtgggcaaagagttcaacaacctcgagaggaggctcgagaatctgaacaagaagatgga agatggcttcctcgatgtgtggacctacaacgctgagctgctggtgctgatggaaaacgagagg acactggacttccatgactccaacgtgaagaacctctacgataaggtgaggatgcagctgagag acaacgccaaggagctgggcaacggctgtttcgagttctaccacaagtgcgacgatgagtgcat gaacagcgtcaaaaacggcacctacgactaccccaaatacgaggaggagagcaagctcaataga aacgagattaagggcgtcaagctgtccaacatgggagtgtaccaa (SEQ ID NO: 59; soluble Z1 (sZ1) nucleic acid sequence). The following amino acid sequence, or a fragment thereof, optionally including a His tag (e.g., six consecutive histidine amino acids), may be added to or included at the carboxy (COOH) terminus of the Z1 HA soluble protein: GYIPEAPRDGQAYVRKDGEWVLLSTFLGSGLNDIFEAQKIEWHEGHHHHHH (SEQ ID NO: 60). The above-noted amino acid sequence, including a His tag (e.g., six consecutive histidine amino acids), that may be added to or included at the carboxy (COOH) terminus of the Z1 HA soluble protein may be encoded by the following nucleic acid sequence: Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 ggctacattcccgaagctcctagagacggccaggcttacgtgaggaaagatggagagtgggtgc tgctgagcacctttctgggcagcggactgaacgatatcttcgaggcccagaagatcgaatggca cgagggacatcatcaccaccatcactgatgaggatcc (SEQ ID NO: 61). The term “Neuraminidase (NA)” refers to an influenza virus membrane glycoprotein. NA is involved in the destruction of the cellular receptor for the viral HA by cleaving terminal sialic acid residues from carbohydrate moieties on the surfaces of infected cells. NA also cleaves sialic acid residues from viral proteins, preventing aggregation of viruses. NA (along with HA) is one of the two major influenza virus antigenic determinants. In embodiments, the influenza virus NA protein antigen is an N1 NA protein antigen or an N2 NA protein antigen. In an embodiment the NA protein antigen is a recombinant or recombinantly produced NA protein antigen. In embodiments, an NA protein antigen or fragment thereof may have at least about or equal to 85%, or at least about or equal to 90%, 95%, 98%, 99%, or greater, amino acid sequence identity to the amino acid sequence of a representative influenza A virus NA protein, an IBV NA protein, or a fragment thereof. In an embodiment, an NA immunogenic protein antigen termed “N1-1” (also “N1I” or “N1-I COBRA”) is used in the pentavalent / octavalent immunogenic / vaccine composition and formulation described herein. N1-I is an N1 neuraminidase (NA) protein, which comprises or consists of the following full length amino acid sequence: N1-I – (full length amino acid sequence, where the stalk and transmembrane domains are underlined): MNPNQKIITIGSICMTIGIASLILQIGNIISIWISHSIQTGNQNQPEICNQSVITYENNTWVNQ TYVNISNTNFVAGQDVTSVKLAGNSSLCPISGWAIYSKDNSIRIGSKGDVFVIREPFISCSHLE CRTFFLTQGALLNDKHSNGTVKDRSPYRTLMSCPIGEAPSPYNSRFESVAWSASACHDGMGWLT IGISGPDNGAVAVLKYNGIITDTIKSWRNNILRTQESECVCVNGSCFTIMTDGPSNGQASYKIF KIEKGKIVKSVELNAPNYHYEECSCYPDTGIVMCVCRDNWHGSNRPWVSFNQNLDYQIGYICSG VFGDNPRPNDGEGSCGPVTVDGANGVKGFSFKYGNGVWIGRTKSNSSRSGFEMIWDPNGWTGTD SDFSVKQDIIAITDWSGYSGSFVQHPELTGLDCIRPCFWVELIRGLPKENTIWTSGSSISFCGV NSDTANWSWPDGAELPFTIDK (SEQ ID NO: 4; N1-I NA full length amino acid sequence). In an embodiment, the stalk and transmembrane domain amino acid sequences, designated in underlined font in the above full length N1-I sequence, are removed. An embodiment of a nucleic acid sequence encoding the full length N1-I NA immunogenic protein antigen is provided, as follows: Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 aagcttatgaaccccaaccagaagatcatcaccatcggcagcatctgtatgaccatcggcatcg ccagcctgatcctgcagatcggcaacatcatcagcatctggatcagccactccatccagaccgg caaccagaaccagcctgagatctgcaaccaaagcgtgatcacctacgagaacaatacctgggtg aatcagacctatgtgaatatcagcaacaccaacttcgtggccggacaggacgtgaccagcgtca agctggccggcaactcctccctgtgccctatttccggctgggccatctacagcaaggacaacag catcagaatcggcagcaagggcgacgtcttcgtgatcagggagcccttcatcagctgcagccat ctggagtgcaggacctttttcctgacacaaggcgccctgctgaacgacaaacattccaacggca ccgtcaaggataggtccccctacaggaccctgatgtcctgtcccatcggcgaagctccctcccc ctacaattccaggttcgagagcgtggcttggtccgcctccgcttgtcacgatggaatgggatgg ctgacaatcggcatcagcggacctgacaacggcgctgtcgccgtgctgaagtacaacggcatca tcaccgacaccatcaagagctggaggaacaacatcctgaggacacaggagagcgaatgtgtctg cgtgaatggctcctgcttcacaatcatgaccgacggcccttccaacggccaggcttcctacaag attttcaagatcgagaagggaaagatcgtgaagtccgtcgagctgaatgcccctaactaccatt acgaagaatgtagctgctaccccgacaccggcatcgtcatgtgcgtgtgcagagataactggca cggaagcaacaggccttgggtgtccttcaatcagaacctcgactatcagatcggatacatttgc tccggcgtcttcggcgacaaccctaggcccaatgacggcgagggcagctgtggacccgtgaccg tggatggcgccaatggcgtgaagggattcagcttcaagtacggaaatggcgtgtggatcggcag gaccaagtccaactccagcaggagcggcttcgagatgatctgggaccctaacggctggacaggc acagacagcgatttctccgtgaagcaggacatcatcgccatcaccgactggtccggctacagcg gcagcttcgtgcagcaccctgagctgaccggactggactgcatcaggccttgcttttgggtgga gctgatcaggggcctgcccaaagagaacaccatttggacctccggaagctccattagcttctgc ggcgtgaatagcgataccgccaactggtcctggcctgacggcgctgagctgccttttaccatcg ataaatgatagggatcc (SEQ ID NO: 19; N1-I full length nucleic acid sequence). The nucleic acid sequence that encodes the stalk and transmembrane domain amino acid sequences, (which may be removed in the amino acid sequence), are designated in underlined font in the above full length N1-I polynucleotide sequence. The amino acid sequence of a soluble form of the N1-I NA immunogenic protein antigen (sN1-I NA) is provided, as follows: N1-I (soluble NA amino acid sequence): MPMGSLQPLATLYLLGMLVASVLSAHHHHHHGSGSLVPRGSPSRSIINETADDIVYRLTVIIDD RYESLKNLITLRADRLEMIINDNVSTILASIGSGTGVAGQDVTSVKLAGNSSLCPISGWAIYSK DNSIRIGSKGDVFVIREPFISCSHLECRTFFLTQGALLNDKHSNGTVKDRSPYRTLMSCPIGEA PSPYNSRFESVAWSASACHDGMGWLTIGISGPDNGAVAVLKYNGIITDTIKSWRNNILRTQESE CVCVNGSCFTIMTDGPSNGQASYKIFKIEKGKIVKSVELNAPNYHYEECSCYPDTGIVMCVCRD Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 NWHGSNRPWVSFNQNLDYQIGYICSGVFGDNPRPNDGEGSCGPVTVDGANGVKGFSFKYGNGVW IGRTKSNSSRSGFEMIWDPNGWTGTDSDFSVKQDIIAITDWSGYSGSFVQHPELTGLDCIRPCF WVELIRGLPKENTIWTSGSSISFCGVNSDTANWSWPDGAELPFTIDK (SEQ ID NO: 9; soluble N1-I (sN1-I) amino acid sequence). In an embodiment, in the sN1-I amino acid sequence above, the underlined font designates the added amino acid sequences and His-tag sequences located at the amino terminus that may be removed from the soluble N1-I protein. An embodiment of a nucleic acid sequence encoding the soluble N1-I NA immunogenic protein antigen is provided, as follows: aagcttatgcccatgggctctctgcagcctctggccacactgtatctgctgggaatgctggtcg ccagcgtgctcagcgctcatcaccatcatcatcacggcagcggctctctggtgcctagaggcag cccttctagaagcattatcaacgagaccgctgacgacatcgtgtacagactcaccgtcatcatc gacgatagatacgaaagcctcaagaatctgatcaccctcagagccgataggctggagatgatca tcaacgacaacgtctccaccattctggcctccattggcagcggtaacttcgtggccggacagga cgtgaccagcgtcaagctggccggcaactcctccctgtgccctatttccggctgggccatctac agcaaggacaacagcatcagaatcggcagcaagggcgacgtcttcgtgatcagggagcccttca tcagctgcagccatctggagtgcaggacctttttcctgacacaaggcgccctgctgaacgacaa acattccaacggcaccgtcaaggataggtccccctacaggaccctgatgtcctgtcccatcggc gaagctccctccccctacaattccaggttcgagagcgtggcttggtccgcctccgcttgtcacg atggaatgggatggctgacaatcggcatcagcggacctgacaacggcgctgtcgccgtgctgaa gtacaacggcatcatcaccgacaccatcaagagctggaggaacaacatcctgaggacacaggag agcgaatgtgtctgcgtgaatggctcctgcttcacaatcatgaccgacggcccttccaacggcc aggcttcctacaagattttcaagatcgagaagggaaagatcgtgaagtccgtcgagctgaatgc ccctaactaccattacgaagaatgtagctgctaccccgacaccggcatcgtcatgtgcgtgtgc agagataactggcacggaagcaacaggccttgggtgtccttcaatcagaacctcgactatcaga tcggatacatttgctccggcgtcttcggcgacaaccctaggcccaatgacggcgagggcagctg tggacccgtgaccgtggatggcgccaatggcgtgaagggattcagcttcaagtacggaaatggc gtgtggatcggcaggaccaagtccaactccagcaggagcggcttcgagatgatctgggacccta acggctggacaggcacagacagcgatttctccgtgaagcaggacatcatcgccatcaccgactg gtccggctacagcggcagcttcgtgcagcaccctgagctgaccggactggactgcatcaggcct tgcttttgggtggagctgatcaggggcctgcccaaagagaacaccatttggacctccggaagct ccattagcttctgcggcgtgaatagcgataccgccaactggtcctggcctgacggcgctgagct gccttttaccatcgataaatgatagggatcc (SEQ ID NO: 14; soluble N1-I (sN1-I) nucleic acid sequence). Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 The nucleic acid sequence that encodes added amino acid sequences and His-tag sequences (which may be removed in the amino acid sequence), are designated in underlined font in the above soluble N1-I polynucleotide sequence. The following amino acid sequence, or a fragment thereof, optionally including a His tag (e.g., six consecutive histidine amino acids), may be added to or included at the amino (N) terminus of the N1I NA soluble protein: MPMGSLQPLATLYLLGMLVASVLSAHHHHHHGSGSLVPRGSPSRSIINETADDIVYRLTVIIDD RYESLKNLITLRADRLEMIINDNVSTILASIGSGTG (SEQ ID NO: 33), in which the amino acids in bold font at the amino terminus designate a CD5 signal sequence; the underlined amino acids designate a 6x His-tag (for purification); the amino acids with dotted underscoring designate a thrombin cleavage site; the italicized amino acids designate a tetrabrachion domain and in which short amino acid linker sequences are included. The above-noted amino acid sequence, including a His tag (e.g., six consecutive histidine amino acids), that may be added to or included at the amino (N) terminus of the N1I NA soluble protein may be encoded by the following nucleic acid sequence: aagcttatgcccatgggctctctgcagcctctggccacactgtatctgctgggaatgctggtcg ccagcgtgctcagcgctcatcaccatcatcatcacggcagcggctctctggtgcctagaggcag cccttctagaagcattatcaacgagaccgctgacgacatcgtgtacagactcaccgtcatcatc gacgatagatacgaaagcctcaagaatctgatcaccctcagagccgataggctggagatgatca tcaacgacaacgtctccaccattctggcctccattggcagcggtaccggc (SEQ ID NO: 64). In an embodiment, an NA immunogenic protein antigen termed “N2A” is used in the octavalent / pentavalent immunogenic / vaccine composition and formulation described herein. N2A is an N2 neuraminidase (NA) protein, which comprises or consists of the following full length amino acid sequence, or a fragment thereof: N2A (full-length amino acid sequence, where the stalk and transmembrane domains are underlined): MNPNQKIITIGSVSLTIATICFLMQIAILVTTVTLHFKQYECSSPPNNQVMLCEPTIIERNITE IVYLTNTTIEKEICPKLAEYRNWSKPQCKITGFAPFSKDNSIRLSAGGDIWVTREPYVSCDPDK CYQFALGQGTTLNNRHSNDTVHDRTPYRTLLMNELGVPFHLGTKQVCIAWSSSSCHDGKAWLHV CITGDDENATASFIYNGRLVDSIGSWSKKILRTQESECVCINGTCTVVMTDGSASGRADTKILF IEEGKIVHISPLSGSAQHVEECSCYPRYPGVRCVCRDNWKGSNRPIVDINVKDYSIVSSYVCSG LVGDTPRKNDSSSSSHCLNPNNEEGGHGVKGWAFDDGNDVWMGRTISEKLRLGYETFKVIEGWS KPNSKLQINRQVIVERGNRSGYSGIFSVEGKSCINRCFYVELIRGRKQETEVWWTSNSIVVFCG TSGTYGTGSWPDGADINLMPI (SEQ ID NO: 65; N2A HA full-length amino acid sequence). Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 In an embodiment, the stalk and transmembrane domain amino acid sequences, designated in underlined font in the above full length N2A sequence, are removed. An embodiment of a nucleic acid sequence encoding the full length N2A NA immunogenic protein antigen is provided, as follows, where nucleotides encoding the stalk and transmembrane domains are underlined: TCTGCTTTCTGATGCAGATCGCCATTCTCGTCACAACAGTCACACTGCACTTCAAGCAGTACGA ATGCAGCTCCCCTCCCAACAACCAAGTGATGCTGTGTGAGCCCACCATCATTGAGAGGAACATC ACAGAAATCGTCTATCTGACCAACACCACCATCGAGAAAGAAATCTGCCCCAAGCTGGCCGAGT ATAGGAACTGGAGCAAGCCCCAGTGCAAGATCACCGGCTTCGCCCCTTTCAGCAAGGACAACAG CATTAGACTGAGCGCTGGAGGCGACATTTGGGTGACAAGAGAGCCCTACGTGAGCTGCGACCCC GATAAGTGTTACCAGTTCGCTCTGGGCCAAGGCACCACACTGAACAATAGACACAGCAACGACA CCGTGCACGACAGAACCCCCTATAGAACACTGCTGATGAACGAGCTCGGCGTGCCCTTCCATCT GGGCACCAAACAAGTGTGTATTGCTTGGAGCAGCAGCAGCTGTCACGATGGCAAGGCTTGGCTG CATGTGTGTATCACCGGCGACGACGAAAACGCTACCGCCAGCTTCATCTACAATGGAAGACTGG TGGACAGCATCGGCAGCTGGTCCAAGAAGATTCTGAGAACCCAAGAGAGCGAATGCGTGTGCAT TAACGGCACATGCACCGTGGTGATGACAGACGGAAGCGCTAGCGGCAGAGCTGACACCAAGATC CTCTTCATCGAGGAGGGCAAGATCGTCCATATCAGCCCTCTGAGCGGAAGCGCTCAGCACGTGG AGGAGTGTAGCTGCTACCCTAGATATCCCGGCGTGAGATGCGTCTGTAGAGACAACTGGAAGGG CAGCAACAGACCCATCGTGGACATCAACGTCAAGGACTACTCCATCGTGAGCAGCTACGTGTGC TCCGGACTGGTGGGAGACACACCTAGAAAGAACGACTCCTCCAGCAGCAGCCACTGTCTGAACC CTAATAACGAGGAGGGAGGCCATGGAGTGAAGGGATGGGCCTTTGATGACGGCAACGACGTCTG GATGGGAAGGACCATTTCCGAGAAACTGAGGCTCGGATACGAGACCTTCAAGGTGATCGAGGGA TGGTCCAAACCCAATAGCAAGCTCCAGATCAATAGACAAGTGATCGTGGAAAGAGGCAACAGAT CCGGCTATAGCGGAATCTTCAGCGTGGAGGGAAAGAGCTGCATCAATAGATGCTTCTACGTGGA GCTGATTAGAGGAAGGAAGCAAGAGACAGAAGTGTGGTGGACCAGCAACTCCATTGTCGTGTTT TGCGGCACAAGCGGAACCTATGGAACCGGCAGCTGGCCCGATGGCGCTGACATCAATCTGATGC CTATCTGATGAGAATTCGGATCC (SEQ ID NO: 66; N2A full-length nucleic acid sequence). The amino acid sequence of a soluble form of the N2A NA immunogenic protein antigen (sN2A NA) is provided, as follows: N2A (soluble NA amino acid sequence): KEICPKLAEYRNWSKPQCKITGFAPFSKDNSIRLSAGGDIWVTREPYVSCDPDKCYQFALGQGT TLNNRHSNDTVHDRTPYRTLLMNELGVPFHLGTKQVCIAWSSSSCHDGKAWLHVCITGDDENAT ASFIYNGRLVDSIGSWSKKILRTQESECVCINGTCTVVMTDGSASGRADTKILFIEEGKIVHIS Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 PLSGSAQHVEECSCYPRYPGVRCVCRDNWKGSNRPIVDINVKDYSIVSSYVCSGLVGDTPRKND SSSSSHCLNPNNEEGGHGVKGWAFDDGNDVWMGRTISEKLRLGYETFKVIEGWSKPNSKLQINR QVIVERGNRSGYSGIFSVEGKSCINRCFYVELIRGRKQETEVWWTSNSIVVFCGTSGTYGTGSW PDGADINLMPI (SEQ ID NO: 67; soluble N2A (sN2A) amino acid sequence). An embodiment of a nucleic acid sequence encoding the soluble N2A NA immunogenic protein antigen is provided, as follows: aaagaaatctgccccaagctggccgagtataggaactggagcaagccccagtgcaagatcaccg gcttcgcccctttcagcaaggacaacagcattagactgagcgctggaggcgacatttgggtgac aagagagccctacgtgagctgcgaccccgataagtgttaccagttcgctctgggccaaggcacc acactgaacaatagacacagcaacgacaccgtgcacgacagaaccccctatagaacactgctga tgaacgagctcggcgtgcccttccatctgggcaccaaacaagtgtgtattgcttggagcagcag cagctgtcacgatggcaaggcttggctgcatgtgtgtatcaccggcgacgacgaaaacgctacc gccagcttcatctacaatggaagactggtggacagcatcggcagctggtccaagaagattctga gaacccaagagagcgaatgcgtgtgcattaacggcacatgcaccgtggtgatgacagacggaag cgctagcggcagagctgacaccaagatcctcttcatcgaggagggcaagatcgtccatatcagc cctctgagcggaagcgctcagcacgtggaggagtgtagctgctaccctagatatcccggcgtga gatgcgtctgtagagacaactggaagggcagcaacagacccatcgtggacatcaacgtcaagga ctactccatcgtgagcagctacgtgtgctccggactggtgggagacacacctagaaagaacgac tcctccagcagcagccactgtctgaaccctaataacgaggagggaggccatggagtgaagggat gggcctttgatgacggcaacgacgtctggatgggaaggaccatttccgagaaactgaggctcgg atacgagaccttcaaggtgatcgagggatggtccaaacccaatagcaagctccagatcaataga caagtgatcgtggaaagaggcaacagatccggctatagcggaatcttcagcgtggagggaaaga gctgcatcaatagatgcttctacgtggagctgattagaggaaggaagcaagagacagaagtgtg gtggaccagcaactccattgtcgtgttttgcggcacaagcggaacctatggaaccggcagctgg cccgatggcgctgacatcaatctgatgcctatctgatgagaattcggatcc (SEQ ID NO: 68; soluble N2A (sN2A) nucleic acid sequence). The following amino acid sequence, or a fragment thereof, optionally including a His tag (e.g., six consecutive histidine amino acids), may be added to or included at the amino (N) terminus of the N2A NA soluble protein: MPMGSLQPLATLYLLGMLVASVLSAHHHHHHGSGSLVPRGSPSRSIINETADDIVYRLTVIIDD RYESLKNLITLRADRLEMIINDNVSTILASIGSGTG (SEQ ID NO: 33), in which the amino acids in bold font at the amino terminus designate a CD5 signal sequence; the underlined amino acids designate a 6x His-tag (for purification); the amino acids with dotted underscoring Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 designate a thrombin cleavage site; the italicized amino acids designate a tetrabrachion domain and in which short amino acid linker sequences are included. The above-noted amino acid sequence, including a His tag (e.g., six consecutive histidine amino acids), that may be added to or included at the amino (N) terminus of the N2A NA soluble protein may be encoded by the following nucleic acid sequence: aagcttatgcccatgggctctctgcagcctctggccacactgtatctgctgggaatgctggtcg ccagcgtgctcagcgctcatcaccatcatcatcacggcagcggctctctggtgcctagaggcag cccttctagaagcattatcaacgagaccgctgacgacatcgtgtacagactcaccgtcatcatc gacgatagatacgaaagcctcaagaatctgatcaccctcagagccgataggctggagatgatca tcaacgacaacgtctccaccattctggcctccattggcagcggtaccggc (SEQ ID NO: 64). In an embodiment, an NA immunogenic protein antigen termed “N2-B” (also “N2-B COBRA”) is used in the pentavalent / octavalent immunogenic / vaccine composition and formulation described herein. N2-B is an N2 neuraminidase (N2 NA) protein, which comprises or consists of the following full length amino acid sequence: N2-B – (full length amino acid sequence): MNPNQKIISIGSVSLTISTICFFMQIAILITTVTLHFKQYEFNSPPNNQVMLCEPTIIERNITE IVYLTNTTIEKEICPKPAEYRNWSKPQCQITGFAPFSKDNSIRLSAGGDIWVTREPYVSCDPDK CYQFALGQGTTLNNVHSNNTVRDRTPYRTLLMNELGVPFHLGTKQVCIAWSSSSCHDGKAWLHV CITGDDKNATASFIYNGRLVDSVVSWSNNILRTQESECVCINGTCTVVMTDGSASGKADTKILF IEEGKIVHTSTLSGSAQHVEECSCYPRYPGVRCVCRDNWKGSNRPIVDINMKDHSIVSSYVCSG LVGDTPRKNDSSSSSHCLNPNNEKGGHGVKGWAFDDGNDVWMGRTINEDSRLGYETFKVIEGWS NPKSKLQINRQVIVDRGNRSGYSGIFSVEGKSCINRCFYVELIRGRKEETEVLWTSNSIVVFCG TSGTYGTGSWPDGADLNLMHI (SEQ ID NO: 5; N2-B NA full length amino acid sequence). In an embodiment, the stalk and transmembrane domain amino acid sequences, designated in underlined font in the above full length N2-B amino acid sequence, are removed. The nucleic acid sequence encoding the full length N2-B NA immunogenic protein antigen is provided, as follows: aagcttatgaaccccaaccagaagatcatcagcatcggcagcgtgtctctgaccatctccacca tctgcttcttcatgcagatcgccattctgatcaccaccgtgacactgcacttcaagcagtacga gttcaacagcccccccaacaatcaagtgatgctgtgcgagcctaccatcatcgagaggaacatc acagagatcgtgtatctgaccaacaccaccatcgagaaagaaatctgccccaagcccgccgagt atagaaactggagcaagccccagtgtcagatcaccggcttcgcccccttctccaaggacaactc catcagactgtccgccggcggcgacatctgggtgacaagggagccttatgtgagctgcgacccc gacaagtgctaccagttcgctctgggccaaggcaccacactcaacaacgtgcactccaacaaca Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 ccgtgagagacagaaccccttatagaacactgctgatgaacgagctgggcgtcccctttcatct gggcacaaaacaagtgtgcatcgcttggtccagcagcagctgccacgatggcaaggcttggctg cacgtctgtattaccggagatgacaagaacgccaccgccagcttcatctacaacggaagactgg tcgatagcgtcgtgagctggagcaataacattctgaggacccaagagtccgagtgcgtctgtat caatggcacatgcaccgtggtgatgacagacggaagcgcctccggcaaagccgacaccaagatt ctgttcatcgaggaaggcaagatcgtgcacaccagcacactgagcggcagcgctcagcacgtgg aggaatgtagctgctatcctagataccccggcgtcagatgcgtgtgtagagacaattggaaggg aagcaatagacccatcgtggacatcaacatgaaggaccacagcattgtcagctcctatgtgtgc tccggactggtcggcgatacccctagaaaaaacgacagcagctccagctcccactgtctgaacc ccaataacgaaaagggaggccatggcgtcaagggctgggcttttgacgacggcaacgacgtgtg gatgggcagaacaatcaatgaggactctagactgggctacgagaccttcaaagtgatcgaggga tggagcaaccccaagagcaagctgcaaatcaatagacaagtgatcgtggataggggaaatagga gcggctacagcggcatcttttccgtggagggcaagagctgcatcaatagatgcttctacgtgga gctgatcagaggaagaaaggaggaaaccgaggtgctgtggacatccaactccattgtggtgttc tgcggcaccagcggaacctacggcaccggcagctggcccgacggagccgacctcaatctgatgc atatttgatgaggatcc (SEQ ID NO: 20; N2-B NA full length nucleic acid sequence). The nucleic acid sequence that encodes the stalk and transmembrane domain amino acid sequences (which may be removed in the amino acid sequence), are designated in underlined font in the above full length N2-B polynucleotide sequence. The amino acid sequence of a soluble form of the N2-B NA immunogenic protein antigen (sN2-B NA) is provided, as follows: N2-B (soluble NA amino acid sequence): MPMGSLQPLATLYLLGMLVASVLSAHHHHHHGSGSLVPRGSPSRSIINETADDIVYRLTVIIDD RYESLKNLITLRADRLEMIINDNVSTILASIGSGTGKEICPKPAEYRNWSKPQCQITGFAPFSK DNSIRLSAGGDIWVTREPYVSCDPDKCYQFALGQGTTLNNVHSNNTVRDRTPYRTLLMNELGVP FHLGTKQVCIAWSSSSCHDGKAWLHVCITGDDKNATASFIYNGRLVDSVVSWSNNILRTQESEC VCINGTCTVVMTDGSASGKADTKILFIEEGKIVHTSTLSGSAQHVEECSCYPRYPGVRCVCRDN WKGSNRPIVDINMKDHSIVSSYVCSGLVGDTPRKNDSSSSSHCLNPNNEKGGHGVKGWAFDDGN DVWMGRTINEDSRLGYETFKVIEGWSNPKSKLQINRQVIVDRGNRSGYSGIFSVEGKSCINRCF YVELIRGRKEETEVLWTSNSIVVFCGTSGTYGTGSWPDGADLNLMHI (SEQ ID NO: 10; soluble N2-B (sN2-B) NA amino acid sequence). In an embodiment, in the N2-B amino acid sequence above, the underlined font designates the added amino acid sequences and His-tag sequences located at the amino terminus that may be removed from the soluble N2-B protein. Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 The nucleic acid sequence encoding the soluble N2-B NA immunogenic protein antigen is provided, as follows: aagcttatgcccatgggctctctgcagcctctggccacactgtatctgctgggaatgctggtcg ccagcgtgctcagcgctcatcaccatcatcatcacggcagcggctctctggtgcctagaggcag cccttctagaagcattatcaacgagaccgctgacgacatcgtgtacagactcaccgtcatcatc gacgatagatacgaaagcctcaagaatctgatcaccctcagagccgataggctggagatgatca tcaacgacaacgtctccaccattctggcctccattggcagcggtaccggcaaggagatctgtcc caagcccgccgagtacagaaactggagcaagccccagtgtcagattaccggattcgcccctttc tccaaggacaactccattagactgtccgccggaggcgacatttgggtgaccagagagccttacg tcagctgtgatcccgataagtgctaccagttcgctctcggccaaggcaccaccctcaacaacgt gcatagcaacaacaccgtgagggatagaacaccctacagaacactgctcatgaacgagctcgga gtgcctttccacctcggcacaaagcaagtgtgcatcgcttggagctccagcagctgccacgatg gaaaggcttggctccacgtgtgtatcaccggcgacgacaagaacgctaccgcctccttcatcta caacggcagactcgtggattccgtggtgagctggtccaacaatattctgaggacacaagagtcc gaatgcgtgtgcatcaatggaacatgcaccgtggtgatgaccgatggaagcgcttccggcaagg ccgacacaaagattctgttcatcgaggagggcaaaatcgtgcacacaagcacactgtccggaag cgctcagcacgtcgaagagtgcagctgctatcctagataccccggcgtgaggtgtgtgtgtaga gacaactggaagggctccaatagacccatcgtcgacatcaacatgaaggatcacagcatcgtca gctcctacgtgtgtagcggactcgtgggagacacccctagaaaaaacgactcctccagcagcag ccactgtctgaaccccaacaatgagaagggaggccatggcgtgaagggctgggcctttgacgac ggaaacgatgtgtggatgggaagaaccattaacgaggattctagactgggctatgagacattca aggtgatcgagggctggagcaaccccaagtccaaactgcagatcaatagacaagtgatcgtgga tagaggcaatagatccggctacagcggcatcttctccgtcgaaggaaagagctgcatcaataga tgcttctacgtggaactgattagaggcagaaaggaggaaacagaggtgctgtggacctccaact ccattgtcgtcttctgtggcaccagcggcacctacggaaccggcagctggcccgacggcgctga tctgaatctgatgcacatttgatgagaattcggatcc (SEQ ID NO: 15; soluble N2-B (sN2-B) NA nucleic acid sequence). The nucleic acid sequence that encodes added amino acid sequences and His-tag sequences (which may be removed in the amino acid sequence), are designated in underlined font in the above soluble N2-B polynucleotide sequence. In some embodiments, truncation of the transmembrane domain for soluble NA proteins is replaced with the following: MPMGSLQPLATLYLLGMLVASVLSAHHHHHHGSGSLVPRGSPSRSIINETADDIVYRLT VIIDDRYESLKNLITLRADRLEMIINDNVSTILASIGSGTG (SEQ ID NO: 33), in which the Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 amino acids in bold font at the amino terminus designate a CD5 signal sequence; the underlined amino acids designate a 6x His-tag (for purification); the amino acids with dotted underscoring designate a thrombin cleavage site; the italicized amino acids designate a tetrabrachion domain and in which short amino acid linker sequences are included, or with the replacement sequences for the truncated transmembrane domain as described, for example, in Example 10. The five COBRA HA and NA influenza virus antigen sequences contained in the pentavalent composition or formulation described and used herein include the following HA and NA influenza virus protein antigens having the above-described sequences: “Y2” (H1 HA), “NG2” (H3 HA), “BC2” (IBV HA), “N1I” or “N1-I” (N1 NA), and “N2B” (N2 NA). In an embodiment, the HA and NA antigens are recombinant and / or are recombinantly produced. In embodiments, portions of the above-described HA and NA antigen sequences to which antibodies bind (a binding portion) are encompassed in the immunogens, compositions / vaccines, formulations, and methods described herein. In an embodiment, the antibodies comprise serum antibodies generated, produced, or elicited in a subject following administration or immunization with the pentavalent immunogen comprising the above-described HA and NA protein antigens (i.e., “Y2” (H1 HA), “NG2” (H3 HA), “BC2” (IBV HA), “N1I” or “N1-I” (N1 NA), and “N2B” (N2 NA)). The eight COBRA HA and NA influenza virus antigen sequences contained in the octavalent composition or formulation described and used herein include the following HA and NA influenza virus protein antigens having the above-described sequences: “Y4” (H1 HA), “NG3” (H3 HA), “N1I” (N1 HA), “N2A” (N2 NA), “BC3” (IBV HA), “Z1” (H2 HA), “IAN8” (H5 HA), and “Q6” (H7 HA). In an embodiment, the HA and NA antigens are recombinant and / or are recombinantly produced. In some embodiments, the “BC3” (IBV HA) influenza virus protein antigen is replaced with a “BC2” (IBV HA) influenza virus protein antigen having the above-described sequences. “Hybridization” means hydrogen bonding, which may be Watson-Crick, Hoogsteen, or reversed Hoogsteen hydrogen bonding, between complementary nucleobases. For example, in DNA, adenine and thymine, and cytosine and guanine, are, respectively, complementary nucleobases that pair through the formation of hydrogen bonds. The term “immune response” is meant any response mediated by an immunoresponsive cell. In one example of an immune response, leukocytes are recruited to carry out a variety of different specific functions in response to exposure to an antigen (e.g., a foreign entity). Immune responses are multifactorial processes that differ depending on the types of cells involved. Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 Immune responses include cell-mediated responses (e.g., T cell responses), humoral responses (B cell / antibody responses), innate responses and combinations thereof. By “immunogen” is meant a compound, composition, or substance which, under appropriate conditions, can elicit or stimulate an immune response, such as the production of antibodies, and / or a T-cell response, in an animal, including compositions that are injected into or otherwise delivered to an animal. As used herein, an “immunogenic composition” is a composition comprising an immunogen (such as an HA and / or NA polypeptide or a polynucleotide encoding such immunogen) or a vaccine comprising an HA and / or NA polypeptide or a polynucleotide encoding such immunogen). As will be appreciated by the skilled person in the art, if administered to a subject in need prior to the subject’s contracting disease or experiencing full-blown disease, an immunogenic composition can be prophylactic and result in the subject’s eliciting an immune response, e.g., a neutralizing antibody and / or cellular immune response, to protect against disease, or to prevent more severe disease or condition, and / or the symptoms thereof. If administered to a subject in need following the subject’s contracting disease, an immunogenic composition can be therapeutic and result in the subject’s eliciting an immune response, e.g., a neutralizing antibody and / or cellular immune response, to treat the disease, e.g., by reducing, diminishing, abrogating, ameliorating, abating, alleviating, or eliminating the disease, and / or the symptoms thereof. In an embodiment, the immune response is a B cell response, which results in the production of antibodies, e.g., neutralizing antibodies, directed against the immunogen or immunogenic composition comprising the antigen or antigen sequence. In a manner similar to the foregoing, in some embodiments, an immunogenic composition or vaccine can be prophylactic. In some embodiments, an immunogenic composition or vaccine can be therapeutic. In an embodiment, the disease is influenza (flu). In an embodiment, the disease is infectious bronchitis. By “immunogenic composition” is meant a composition comprising an antigen, antigen sequence, or immunogen, wherein the composition elicits an immune response in an immunized subject. The term “immunize” (or immunization) refers to rendering a subject protected from, or immunologically responsive to, a disease or pathology caused by a pathogenic agent, e.g., an infectious disease caused by a virus, e.g., influenza virus H1, H2, H3, H5, H7, or IBV, such as by immunization / vaccination. In an embodiment, a “prime and pull” mechanism of vaccination, immunization, or administration of a treatment (e.g., with an agent, drug, biological, compound, or molecule) may assist in reducing the spread of infection and preventing recurrent symptoms caused by mucosal viruses. Briefly, a prime-pull method involves a first step of administering to Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 a subject a conventional vaccination / immunization (e.g., intramuscular) to “prime” and initiate a systemic T-cell response. Second, a topical preparation or composition, e.g., a cream, ointment, lotion, and the like, containing one or more ingredients, agents, or medications that attracts or “pulls” T-cells to the site of viral growth is applied onto or under the skin. The method establishes an existing pool of protective memory T-cells within peripheral tissue where T-cells migrate and where entry might naturally be restricted. It has been demonstrated that tissue- resident memory T-cells are more efficacious in combatting disease and infectious agents than circulating memory T-cells, in part, because of their tissue localization. (Bernstein, D.I. et al., 2019, npj Vaccines, Vol.4, No.33; pages 1-10; Shamseldin, M.M. et al., 2023, J. Immunology, Vol.210, Issue 9, 1257-1271). By “increase” is meant to alter positively relative to a reference. An increase may be by 1%, 5%, 10%, 25%, 30%, 50%, 75%, 100%, or more, or by 1.5-fold, -fold 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 25-fold, 50-fold, 75-fold, 100-fold, or more. The term “influenza virus” refers to a segmented negative-strand RNA virus that belongs to the Orthomyxoviridae family of viruses. There are three types of Influenza viruses: A, B (IBV) and C. Influenza A viruses infect a wide variety of birds and mammals, including humans, horses, marine mammals, pigs, ferrets, and chickens. In animals, most influenza A viruses cause mild localized infections of the respiratory and intestinal tract. However, highly pathogenic influenza A strains, such as, without limitation, H1N1, H1N2, H2N1, H2N2, H2N3, H7N3, H7N7, H3N2, H3N1, H5N1, H5N2, H5N6, H5N8, H7N9, H9N2, and related viruses cause systemic infections in poultry in which mortality may reach 100%. H5N1 is also referred to as “avian influenza.” By “inhibitory nucleic acid” is meant a double-stranded RNA, siRNA, shRNA, or antisense RNA, or a portion thereof, or a mimetic thereof, that when administered to a mammalian cell results in a decrease (e.g., by 5%, 10%, 25%, 50%, 75%, or even 90-100%) in the expression of a target gene. Typically, a nucleic acid inhibitor comprises at least a portion of a target nucleic acid molecule, or an ortholog thereof, or comprises at least a portion of the complementary strand of a target nucleic acid molecule. For example, an inhibitory nucleic acid molecule comprises at least a portion of any or all of the nucleic acids delineated herein. The terms “isolated,” “purified,” or “biologically pure” refer to material that is free to varying degrees from components which normally accompany it as found in its native state. “Isolate” denotes a degree of separation from original source or surroundings. “Purify” denotes a degree of separation that is higher than isolation. A “purified” or “biologically pure” protein is sufficiently free of other materials such that any impurities do not materially affect the biological Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 properties of the protein or cause other adverse consequences. That is, a nucleic acid, protein, or peptide is purified if it is substantially free of cellular material, debris, non-relevant viral material, or culture medium when produced by recombinant DNA techniques, or of chemical precursors or other chemicals when chemically synthesized. Purity and homogeneity are typically determined using standard purification methods and analytical chemistry techniques, for example, polyacrylamide gel electrophoresis or high-performance liquid chromatography. The term “purified” can denote that a nucleic acid or protein gives rise to essentially one band in an electrophoretic gel. For a protein that can be subjected to modifications, for example, phosphorylation or glycosylation, different modifications may give rise to different isolated proteins, which can be separately purified. The term “isolated” also embraces recombinant nucleic acids, recombinant or recombinantly produced proteins, or viruses, as well as chemically synthesized nucleic acids, polypeptides, or peptides. By “isolated polynucleotide” is meant a nucleic acid (e.g., a DNA molecule) that is free of the genes which flank the gene in the naturally-occurring genome of the organism from which the nucleic acid molecule of the disclosure is derived. In some cases, the nucleic acid is a DNA molecule. The term therefore includes, for example, a recombinant DNA that is incorporated into a vector; into an autonomously replicating plasmid or virus; or into the genomic DNA of a prokaryote or eukaryote; or that exists as a separate molecule (for example, a cDNA or a genomic or cDNA fragment produced by PCR or restriction endonuclease digestion) independent of other sequences. In addition, the term includes an RNA molecule that is transcribed from a DNA molecule, as well as a recombinant DNA that is part of a hybrid gene encoding additional polypeptide sequence. By an “isolated polypeptide” is meant a polypeptide, such as described herein, that has been separated from components that naturally accompany it. Typically, the polypeptide is isolated when it is at least 30% by weight, at least 40%, by weight, at least 50%, by weight, at least 60%, by weight, free from the proteins and naturally-occurring organic molecules with which it is naturally associated. In some embodiments, an isolated polypeptide preparation is at least 75%, at least 90%, or at least 99%, by weight, free from the proteins and naturally- occurring organic molecules with which it is naturally associated. An isolated polypeptide may be obtained, for example, by extraction from a natural source; by expression of a recombinant nucleic acid encoding such a polypeptide; or by chemically synthesizing the protein. Purity can be measured by any standard, appropriate method, for example, column chromatography, polyacrylamide gel electrophoresis, or by high performance liquid chromatography (HPLC) Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 analysis. An isolated polypeptide can refer to broadly active virus immunogen polypeptide generated by the methods described herein. By “linker” is meant one or more amino acids that serve as a spacer between two polypeptides or peptides of a fusion protein. By “marker” is meant any protein or polynucleotide having an alteration (e.g., increase or reduction) in expression level or activity that is associated with a disease, condition, pathology, or disorder. A “Matrix (M1) protein” refers to an influenza virus structural protein found within the viral envelope. M1 is thought to function in assembly and budding of virus following infection of a cell. A “mucoadhesive” refers in general to mucoadhesive polymers or compounds which improve retention on dynamic biological substrates such as mucosal surfaces and mucous membranes, particularly for the delivery of an agent, biological molecule, drug, or compound, to mucosal surfaces, such as the nasal cavity (V. Grabovac et al., 2005, Adv Drug Deliv Rev., 57(11): 1713-1723; S. Roy et al., 2009, Designed Monomers and Polymers, 12, 483-495). Mucoadhesive polymers or compounds typically have numerous hydrophilic groups, such as hydroxyl, carboxyl, amide, and sulfate, which attach to mucus or the cell membrane by various interactions such as hydrogen bonding, hydrophobic interactions, or electrostatic interactions. The nasal cavity provides a direct route for mucoadhesive administration. Nasal mucus has a quick turnover of 10 to 15 minutes, particularly because of the sweeping motion of the cilia that line the mucosa. The close proximity of the nasal passages to the blood-brain barrier offers a convenient route for administering drugs to the central nervous system. While gels, solutions, and aerosols are commonly used as dosage forms in the nasal cavity, muco-adhesives, which are commercially available, may be used for increased bioavailability in mucosal areas to which biological agents and drugs are delivered. In embodiments, muco-adhesives may be used in conjunction with particles and microspheres as known in the art. As used herein, “obtaining” as in “obtaining an agent” includes synthesizing, isolating, purifying, purchasing, or otherwise acquiring the agent. The term “operably linked” refers to nucleic acid sequences as used herein. By way of example, a first nucleic acid sequence is operably linked to a second nucleic acid sequence when the first nucleic acid sequence is placed in a functional relationship with the second nucleic acid sequence. For instance, a promoter is operably linked to a coding sequence if the promoter affects (allows) the transcription or expression of the coding sequence. Generally, operably Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 linked DNA sequences are contiguous and, where necessary to join two protein-coding regions, are in the same reading frame. The nucleotide sequence encoding an HA or NA protein (e.g., recombinant protein) that is broadly reactive (such that an immune response (e.g., an antibody response) is generated against it as well as other, perhaps antigenically drifted, yet related viruses) can be optimized for expression in mammalian cells via codon-optimization and RNA optimization (such as to increase RNA stability) using procedures and techniques practiced in the art. An isolated, broadly reactive, immunogenic antigen, such as influenza (e.g., H1, H2, H3, H5, H7, and / or IBV) hemagglutinin (HA) protein for eliciting an immune response in a subject possesses a collective set of strongly immunogenic epitopes (also called antigenic determinants). An influenza virus HA protein described herein is suitable for use as an immune response- eliciting immunogen, or vaccine, which elicits a broadly reactive immune response, e.g., a neutralizing antibody response, against other related, but nonidentical, virus types which express HA proteins on the viral surface, when introduced into a host subject, in particular, a human subject infected with influenza H1, H2, H3, H5, H7, or IBV virus. The immunogenic antigen (or vaccine) is advantageous for providing an anti-virus immunogen (or a vaccine) that elicits a broadly active immune response against other H1, H2, H3, H5, H7, or IBV influenza virus HA antigens with antigenic variability and similarity, and treats or protects against infection and disease caused by more than one H1, H2, H3, H5, H7, or IBV influenza virus subtype. Similarly, an isolated, broadly reactive influenza neuraminidase (NA) protein such as described herein provides an influenza NA antigen that possesses a collective set of strongly immunogenic epitopes (antigenic determinants) and is suitable for use as an immunogen, such as a vaccine or VLPs, which elicits a broadly reactive immune response, e.g., a neutralizing antibody response, against a plurality of virus types (e.g., influenza virus types) which express NA proteins on the viral surface. The immunogenic NA antigen (or vaccine) is advantageous for treating or protecting against infection and disease caused by different influenza virus types and subtypes. As described herein, five / eight different HA and NA influenza virus antigen sequences are used in a pentavalent / octavalent composition or formulation as described and used herein. The pentavalent composition or formulation includes the following isolated, HA and NA influenza virus protein antigens which are immunogenic and comprise the sequences as set forth hereinabove: “Y2” (H1 HA), “NG2” (H3 HA), “BC2” (IBV HA), “N1I” or “N1-I” (N1 NA), and “N2B” (N2 NA). The octavalent composition or formulation includes the following isolated, HA and NA influenza virus protein antigens which are immunogenic and comprise the sequences as set forth herein: “Y4” (H1 HA), “NG3” (H3 HA), “N1I” (N1 HA), “N2A” (N2 Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 NA), “BC3” (IBV HA), “Z1” (H2 HA), “IAN8” (H5 HA), and “Q6” (H7 HA). In an embodiment, “BC3” is replaced with “BC2” (IBV HA) comprising the sequences as set forth herein. In an embodiment, these HA and NA antigens are recombinant and / or are recombinantly produced. By “open reading frame (ORF)” is meant a series of nucleotide triplets (codons) that code for amino acids without any termination codons. These series of codons are usually translatable into a peptide or polypeptide. The term “pharmaceutically acceptable vehicle” refers to conventional carriers (vehicles) and excipients that are physiologically and pharmaceutically acceptable for use, particularly in mammalian, e.g., human, subjects, as well as in other animal or avian subjects. Such pharmaceutically acceptable vehicles are known to the skilled practitioner in the pertinent art and can be readily found in Remington's Pharmaceutical Sciences, by E. W. Martin, Mack Publishing Co., Easton, Pa., 15th Edition (1975) and its updated editions, which describes compositions and formulations suitable for pharmaceutical delivery of one or more therapeutic compositions, such as one or more influenza immunogens (vaccines), and additional pharmaceutical agents. In general, the nature of a pharmaceutically acceptable carrier depends on the particular mode of administration being employed. For instance, parenteral formulations usually comprise injectable fluids / liquids that include pharmaceutically and physiologically acceptable fluids such as water, physiological saline, balanced salt solutions, aqueous dextrose, glycerol or the like as a vehicle or diluent. For solid compositions (for example, powder, pill, tablet, or capsule forms), conventional non-toxic solid carriers may include, for example, pharmaceutical grades of mannitol, lactose, starch, or magnesium stearate, which typically stabilize and / or increase the half-life of a composition or drug. In addition to biologically- neutral carriers, pharmaceutical compositions to be administered can contain minor amounts of non-toxic auxiliary substances, such as wetting or emulsifying agents, preservatives, and pH buffering agents and the like, for example sodium acetate or sorbitan monolaurate. By “plasmid” is meant a circular nucleic acid molecule capable of autonomous replication in a host cell. By “polypeptide” (or protein) is meant a polymer in which the monomers comprise amino acid residues that are joined together through amide bonds. When the amino acids are alpha-amino acids, either the L-optical isomer or the D-optical isomer can be used. The terms “polypeptide” or “protein” as used herein are intended to encompass any amino acid sequence and include modified sequences such as glycoproteins. The term “polypeptide” is specifically intended to cover naturally occurring proteins, as well as those which are recombinantly or Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 synthetically produced. The term “residue” or “amino acid residue” also refers to an amino acid that is incorporated into a protein, polypeptide, or peptide. Conservative amino acid substitutions are those substitutions that, when made, least interfere with the properties of the original protein, that is, the structure and especially the function of the protein is conserved and is not significantly changed by such substitutions. Examples of conservative amino acid substitutions are known in the art, e.g., as set forth in, for example, U.S. Publication No.2015 / 0030628. Conservative substitutions generally maintain (a) the structure of the polypeptide backbone in the area of the substitution, for example, as a sheet or helical conformation; (b) the charge or hydrophobicity of the molecule at the target site; and / or (c) the bulk of the side chain. The substitutions that are generally expected to produce the greatest changes in protein properties are non-conservative, for instance, changes in which (a) a hydrophilic residue, for example, seryl or threonyl, is substituted for (or by) a hydrophobic residue, for example, leucyl, isoleucyl, phenylalanyl, valyl or alanyl; (b) a cysteine or proline is substituted for (or by) any other residue; (c) a residue having an electropositive side chain, for example, lysyl, arginyl, or histadyl, is substituted for (or by) an electronegative residue, for example, glutamyl or aspartyl; or (d) a residue having a bulky side chain, for example, phenylalanine, is substituted for (or by) one not having a side chain, for example, glycine. “Primer set” means a set of oligonucleotides that may be used, for example, for PCR. A primer set would consist of at least 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 30, 40, 50, 60, 80, 100, 200, 250, 300, 400, 500, 600, or more primers. By “promoter” is meant an array of nucleic acid control sequences, which direct transcription of a nucleic acid. A promoter includes necessary nucleic acid sequences near the start site of transcription. A promoter also optionally includes distal enhancer or repressor sequence elements. A “constitutive promoter” is a promoter that is continuously active and is not subject to regulation by external signals or molecules. In contrast, the activity of an “inducible promoter” is regulated by an external signal or molecule (for example, a transcription factor). By way of example, a promoter may be a CMV promoter. As will be appreciated by the skilled practitioner in the art, the term “purified” does not require absolute purity; rather, it is intended as a relative term. Thus, for example, a purified peptide, protein, virus, polynucleotide, or other active compound is one that is isolated in whole or in part from naturally associated proteins and other contaminants. In certain embodiments, the term “substantially purified” refers to a peptide, protein, virus, polynucleotide, or other active compound that has been isolated from a cell, cell culture medium, or other crude preparation and Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 subjected to routine methods, such as, without limitation, fractionation, chromatography, or electrophoresis, to remove various components of the initial preparation, such as proteins, cellular debris, and other components. A “recombinant” nucleic acid, protein or virus is one that has a sequence that is not naturally occurring or that has a sequence that is made by an artificial combination of two otherwise separated segments of sequence. Such an artificial combination is often accomplished by chemical synthesis or by the artificial manipulation of isolated segments of nucleic acids, for example, by genetic engineering techniques. A “non-naturally occurring” nucleic acid, protein or virus is one that may be made via recombinant technology, artificial manipulation, genetic or molecular biological engineering, or molecular synthesis procedures and techniques, such as those commonly practiced in the art. By “reduces” is meant a negative alteration (e.g., decrease or reduction) of at least 5%, 10%, 25%, 30%, 40%, 50%, 75%, 80%, 85%, 90%, 95%, 98%, or 100%. By “reference” is meant a standard or control condition. Non-limiting examples of references include a wildtype or nonmutated protein or polynucleotide. In some embodiments, a reference is an immunogen lacking one or more components of an octavalent immunogen or vaccine of the disclosure (e.g., an adjuvant or an antigen). In some cases, a reference is an animal known to be immunized against a particular infectious agent (e.g., an influenza virus of interest) or known to have not been previously exposed to said infectious agent. A “reference sequence” is a defined sequence used as a basis for sequence comparison. In various embodiments, a sequence shares about or at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.9% or greater sequence identity to a reference sequence. In some cases, a sequence contains 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid or nucleotide alterations relative to a reference sequence. A reference sequence may be a subset of or the entirety of a specified sequence; for example, a segment of a full-length cDNA or gene sequence, or the complete cDNA or gene sequence. For polypeptides, the length of the reference polypeptide sequence will generally be at least about 16 amino acids, at least about 20 amino acids, at least about 25 amino acids, or about 35 amino acids, about 50 amino acids, or about 100 amino acids. For nucleic acids, the length of the reference nucleic acid sequence will generally be at least about 50 nucleotides, at least about 60 nucleotides, at least about 75 nucleotides, at least about 100 nucleotides or about 300 nucleotides or any integer thereabout or therebetween. A compound or antibody that “specifically binds” refers to one that recognizes and binds to a polypeptide, such as a virus polypeptide, peptide, or vaccine product, but which does not Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 substantially recognize and bind to other molecules in a sample, for example, a biological sample, which naturally includes a polypeptide, such as a virus polypeptide or peptide. Nucleic acid molecules useful in the methods described herein include any nucleic acid molecule that encodes a polypeptide as described, or a fragment thereof. Such nucleic acid molecules need not be 100% identical with an endogenous nucleic acid sequence but will typically exhibit substantial identity. Polynucleotides having “substantial identity” to an endogenous sequence are typically capable of hybridizing with at least one strand of a double- stranded nucleic acid molecule. By “hybridize” is meant pairing to form a double-stranded molecule between complementary polynucleotide sequences (e.g., a gene), or portions thereof, under various conditions of stringency. (See, e.g., Wahl, G. M. and S. L. Berger, (1987), Methods Enzymol., 152:399; Kimmel, A. R., (1987), Methods Enzymol.152:507). By way of example, stringent salt concentration will ordinarily be less than about 750 mM NaCl and 75 mM trisodium citrate, less than about 500 mM NaCl and 50 mM trisodium citrate, or less than about 250 mM NaCl and 25 mM trisodium citrate. Low stringency hybridization can be obtained in the absence of organic solvent, e.g., formamide, while high stringency hybridization can be obtained in the presence of at least about 35% formamide, or at least about 50% formamide. Stringent temperature conditions will ordinarily include temperatures of at least about 30°C, of at least about 37°C, or of at least about 42°C. Varying additional parameters, such as hybridization time, the concentration of detergent, e.g., sodium dodecyl sulfate (SDS), and the inclusion or exclusion of carrier DNA, are well known to those skilled in the art. Various levels of stringency are accomplished by combining these various conditions as needed. In an embodiment, hybridization will occur at 30°C in 750 mM NaCl, 75 mM trisodium citrate, and 1% SDS. In another embodiment, hybridization will occur at 37°C in 500 mM NaCl, 50 mM trisodium citrate, 1% SDS, 35% formamide, and 100 μg / ml denatured salmon sperm DNA (ssDNA). In another embodiment, hybridization will occur at 42°C in 250 mM NaCl, 25 mM trisodium citrate, 1% SDS, 50% formamide, and 200 μg / ml ssDNA. Useful variations of these conditions will be readily apparent to those skilled in the art. For most applications, washing steps that follow hybridization will also vary in stringency. Wash stringency conditions can be defined by salt concentration and by temperature. As above, wash stringency can be increased by decreasing salt concentration or by increasing temperature. For example, stringent salt concentration for the wash steps may be less than about 30 mM NaCl and 3 mM trisodium citrate, or less than about 15 mM NaCl and 1.5 mM trisodium citrate. Stringent temperature conditions for the wash steps will ordinarily include a temperature of at least about 25°C, of at least about 42°C, or of at least about 68°C. In an embodiment, wash Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 steps will occur at 25°C in 30 mM NaCl, 3 mM trisodium citrate, and 0.1% SDS. In another embodiment, wash steps will occur at 42 C in 15 mM NaCl, 1.5 mM trisodium citrate, and 0.1% SDS. In an embodiment, wash steps will occur at 68°C in 15 mM NaCl, 1.5 mM trisodium citrate, and 0.1% SDS. Additional variations of these conditions will be readily apparent to those skilled in the art. Hybridization techniques are well known to those skilled in the art and are described, for example, in Benton and Davis (Science 196:180, 1977); Grunstein and Hogness (Proc. Natl. Acad. Sci., USA 72:3961, 1975); Ausubel et al. (Current Protocols in Molecular Biology, Wiley Interscience, New York, 2001); Berger and Kimmel (Guide to Molecular Cloning Techniques, 1987, Academic Press, New York); and Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, New York. By “substantially identical” is meant a polypeptide or nucleic acid molecule exhibiting at least 50% identity to a reference amino acid sequence (for example, any one of the amino acid sequences described herein) or nucleic acid sequence (for example, any one of the nucleic acid sequences described herein). In some embodiments, such a sequence is at least 60%, or at least 80% or 85%, or at least or equal to 90%, 95% or even 99% identical at the amino acid level or nucleic acid to the sequence used for comparison. “Sequence identity” refers to the similarity between amino acid or nucleic acid sequences that is expressed in terms of the similarity between the sequences. Sequence identity is frequently measured in terms of percentage identity (or similarity or homology); the higher the percentage, the more similar the sequences are. Homologs or variants of a given gene or protein will possess a relatively high degree of sequence identity when aligned using standard methods. Sequence identity is typically measured using sequence analysis software (for example, Sequence Analysis Software Package of the Genetics Computer Group, University of Wisconsin Biotechnology Center, 1710 University Avenue, Madison, Wis.53705, BLAST, BESTFIT, GAP, or PILEUP / PRETTYBOX programs). Such software matches identical or similar sequences by assigning degrees of homology to various substitutions, deletions, and / or other modifications. Conservative substitutions typically include substitutions within the following groups: glycine, alanine; valine, isoleucine, leucine; aspartic acid, glutamic acid, asparagine, glutamine; serine, threonine; lysine, arginine; and phenylalanine, tyrosine. In an exemplary approach to determining the degree of identity, a BLAST program may be used, with a probability score between e-3and e-100indicating a closely related sequence. In addition, other programs and alignment algorithms are described in, for example, Smith and Waterman, 1981, Adv. Appl. Math.2:482; Needleman and Wunsch, 1970, J. Mol. Biol.48:443; Pearson and Lipman, 1988, Proc. Natl. Acad. Sci. U.S.A.85:2444; Higgins and Sharp, 1988, Gene 73:237- Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 244; Higgins and Sharp, 1989, CABIOS 5:151-153; Corpet et al., 1988, Nucleic Acids Research 16:10881-10890; Pearson and Lipman, 1988, Proc. Natl. Acad. Sci. U.S.A.85:2444; and Altschul et al., 1994, Nature Genet.6:119-129. The NCBI Basic Local Alignment Search Tool (BLAST™) (Altschul et al.1990, J. Mol. Biol.215:403-410) is readily available from several sources, including the National Center for Biotechnology Information (NCBI, Bethesda, Md.) and on the Internet, for use in connection with the sequence analysis programs blastp, blastn, blastx, tblastn and tblastx. By “subject” is meant a vertebrate animal, e.g., a mammal, including, but not limited to, a human, a non-human primate, or a non-human animal or mammal, such as a bovine, equine, canine, ferret, ovine, or feline mammal, or a sheep, goat, llama, camel, or a rodent (rat, mouse), gerbil, or hamster. A “subject” may also refer to a non-human animal, or to an avian vertebrate animal. Non-human subjects or non-human animal subjects may also be referred to as “veterinary subjects.” In a nonlimiting example, a subject is one who is infected with a pathogen, such as influenza virus, e.g., an H1, H2, H3, H5, H7, or IBV virus, or who is at risk of infection by such virus, or who is susceptible to such infection. In some aspects as described herein, the subject is a human subject, such as a patient. In some aspects as described herein, the subject is a non-human subject, such as a non-human animal subject or a veterinary subject. Ranges provided herein are understood to be shorthand for all of the values within the range. For example, a range of 1 to 50 is understood to include any number, combination of numbers, or sub-range from the group consisting 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or greater, consecutively, such as to 100 or greater, inclusive of the first and last values and those in between. As used herein, the terms “treat,” treating,” “treatment,” and the like refer to reducing, diminishing, decreasing, abating, abrogating, alleviating, ameliorating, or eliminating, a disease, condition, disorder, or pathology, and / or symptoms associated therewith. While not intending to be limiting, “treating” typically relates to a therapeutic intervention that occurs after a disease, condition, disorder, or pathology, and / or symptoms associated therewith, have begun to develop so as to reduce the severity of the disease, etc., and the associated signs and symptoms. It will be appreciated that, although not precluded, treating a disorder or condition does not require that the disease, condition, disorder, pathology, or the symptoms associated therewith, be completely eliminated. As used herein, the terms “prevent,” “preventing,” “prevention,” “prophylactic treatment” and the like, refer to inhibiting or blocking a disease state, or the full or full-blown Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 development of a disease in a subject, or reducing the probability of developing a disease, disorder or condition in a subject, who does not have, but is at risk of developing, or is susceptible to developing, a disease, disorder, or condition. As referred to herein, a “transformed” cell is a cell into which a nucleic acid molecule or polynucleotide has been introduced by molecular biology techniques. As used herein, the term “transformation” encompasses all techniques by which a nucleic acid molecule or polynucleotide may be introduced into such a cell, including transfection with viral vectors, transformation with plasmid vectors, and introduction of naked nucleic acid (DNA or RNA) by electroporation, lipofection, and particle gun acceleration. In some cases, the terms “transformation,” “transduction,” and “transfection” are used interchangeably as would be understood by the skilled practitioner in the art. By “vaccine” is meant a preparation of immunogenic material (e.g., protein or nucleic acid), such as a protein or peptide antigen, or a polynucleotide, capable of stimulating (eliciting) an immune response, administered to a subject to treat a disease, condition, or pathology, or to prevent or protect against a disease, condition, or pathology, such as an infectious disease, e.g., a virus infection. The immunogenic material may include, for example, attenuated or killed microorganisms (such as attenuated viruses), or antigenic proteins, peptides, DNA or RNA derived from such microorganisms. Vaccines may elicit a prophylactic (preventative) immune response in the subject; they may also elicit a therapeutic response immune response in a subject. As mentioned above, methods of vaccine administration vary according to the vaccine, and can include routes or means, such as inoculation (intravenous or subcutaneous injection), ingestion, inhalation, intranasal, intramuscular, sublingual, or other forms of administration as known and practiced in the medical art, or as described herein. Inoculations can be delivered by any of a number of routes, including mucosal, such as, for example, intranasal, or parenteral, such as, for example, intravenous, subcutaneous, intramuscular, intradermal, or transdermal. Vaccines may also be administered with an adjuvant to boost the immune response. Vaccines may be administered to human subjects, non-human subjects, or veterinary subjects. To “vaccinate” a subject is to administer a vaccine to the subject. Genetically engineered viral vaccines allow for the combination of multiple protective antigens, such as viral antigens (e.g., HA and / or NA) into one (or more than one) viral vector. Such viral vectors may be employed to generate protection against disease associated with or caused by a broad range of virus types, subtypes, and / or strains. In general, a “multivalent” vaccine (also known as a “polyvalent” vaccine) constitutes an agent that is effective against and / or provides protection against different types of the same organism, such as a virus, or Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 against disease or pathology associated with infection by different types of the same organism, such as a virus. In an embodiment, a pentavalent / octavalent vector vaccine refers to five or eight antigens from different strains (serotypes / serogroups) of a pathogen (e.g., a virus, such as an IAV or IBV influenza virus) or encoding the polynucleotides thereof, contained in a single vector or in more than one vector to immunize a subject against a disease associated with or caused by the pathogen. (See, e.g., K.B. Lauer et al., 2017, Clin. Vaccine Immunol., 24(1):e00298-16). In an embodiment, a pentavalent / octavalent viral vector vaccine induces immunity and / or induces a more robust or potent immune response in a subject to more than one strains, types, or subtypes of a disease-causing pathogen, e.g., influenza virus. In an embodiment, a pentavalent / octavalent viral vector vaccine induces a more robust or potent immune response in a subject to one or more than one strain, type, or subtype of a disease- causing pathogen, such as a virus, e.g., influenza virus, because the vaccine contains five / eight virus HA and / or NA antigens (or encoding polynucleotides) derived from the same or different virus strains, types, or subtypes. The terms “vaccine” and “immunogen” are used interchangeably herein. In an embodiment, a multivalent immunogen / vaccine is a pentavalent / octavalent immunogen / vaccine which contains five (5) or eight (8) influenza polypeptide antigens (or polynucleotides encoding the antigens), including a mixture of influenza HA and / or NA immunogenic polypeptide antigens as described and exemplified herein derived from influenza viruses of certain types or subtypes. Accordingly, in a particular embodiment, the influenza immunogen / vaccine preparation is pentavalent or octavalent. In an embodiment, all of the influenza antigenic proteins (or encoding polynucleotides) contained in the pentavalent / octavalent influenza immunogen or vaccine are of different influenza virus strains or subtypes. In an embodiment, the influenza antigenic proteins (or encoding polynucleotides) contained in the pentavalent / octavalent influenza immunogen or vaccine are influenza hemagglutinin (HA) and / or neuraminidase (NA) antigenic proteins (or encoding polynucleotides), e.g., a mixture of five or eight different influenza HA and / or NA antigenic proteins (or encoding polynucleotides). As used herein, the term “vector” refers to a means of introducing a nucleic acid molecule into a cell, resulting in a transformed cell. Vectors include plasmids (a circular nucleic acid molecule capable of autonomous replication in a host cell), transposons, phages, viruses, liposomes, lipid nanoparticles, and episomes. In some cases, the vector is a nucleic acid (polynucleotide) molecule into which foreign nucleic acid can be inserted without disrupting the ability of the vector to replicate in and / or integrate into a host cell. A vector can include nucleic acid sequences that permit it to replicate in a host cell, such as an origin of replication. An Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 insertional vector can insert itself into a host nucleic acid. A vector can also include one or more selectable marker genes and other genetic elements. An expression vector is a vector that contains the necessary regulatory sequences to allow transcription and translation of inserted gene or genes in a host cell. In some embodiments of the present disclosure, the vector encodes an influenza HA, NA, or M1 protein. In some embodiments, the vector is the pTR600 expression vector (U.S. Patent Application Publication No.2002 / 0106798; Ross et al., 2000, Nat Immunol. 1(2):102-103; and Green et al., 2001, Vaccine 20:242-248). By “virus-like particle (VLP)” is meant virus particles made up of one of more viral structural proteins but lacking the viral genome. Because VLPs lack a viral genome, they are non-infectious and yield safer and potentially more-economical vaccines and vaccine products. In addition, VLPs can often be produced by heterologous expression and can be easily purified. Most VLPs comprise at least a viral core protein that drives budding and release of particles from a host cell. One example of such a core protein is influenza M1. In some embodiments herein, an influenza VLP comprises the HA, NA, and / or M1 proteins. As described herein, influenza VLPs can be produced by transfection of host cells with plasmids encoding the HA, NA, and / or M1 proteins. After incubation of the transfected cells for an appropriate time to allow for protein expression (such as for approximately 72 hours), VLPs can be isolated from cell culture supernatants. By way of example, a protocol for purifying or isolating influenza VLPs from cell supernatants involves low speed centrifugation (to remove cell debris), vacuum filtration and ultracentrifugation of the VLPs through 20% glycerol. A virus-like particle may also include a subviral particle (SVP), which is typically smaller in size than a virus and constitutes a particle without a virus capsid or genome. Unless specifically stated or obvious from context, as used herein, the term “or” is understood to be inclusive. Unless specifically stated or obvious from context, as used herein, the terms “a”, “an”, and “the” are understood to be singular or plural. Similarly, the word “or” is intended to include “and” unless the context clearly indicates otherwise. Hence “comprising A or B” means including A, or B, or A and B. It is further to be understood that all base sizes or amino acid sizes, and all molecular weight or molecular mass values, given for nucleic acids or polypeptides are approximate, and are provided for description. Unless specifically stated or obvious from context, as used herein, the term “about” is understood as within a range of normal tolerance in the art, for example within 2 standard deviations of the mean. About may be understood as being within 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.1%, 0.05%, or 0.01% of the stated value. Unless otherwise clear from context, all numerical values provided herein are modified by the term about. Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 The recitation of a listing of chemical groups in any definition of a variable herein includes definitions of that variable as any single group or combination of listed groups. The recitation of an embodiment for a variable or aspect herein includes that embodiment as any single embodiment or in combination with any other embodiments or portions thereof. Any compositions or methods provided herein can be combined with one or more of any of the other compositions and methods provided herein. BRIEF DESCRIPTION OF THE DRAWINGS FIGs.1A-1C show bar graphs of serum hemagglutinin inhibiting (HAI) antibody titers generated in pre-immune mice after vaccination / immunization against seasonal influenza viruses. In brief, DBA / 2J mice (n=11) were previously infected with A / Singapore / 1986, A / Panama / 1999, and B / Hong Kong / 2001 strains of virus 42 days prior to vaccination. Mice were vaccinated / immunized with the COBRA HA and NA antigen formulation (composition) intranasally twice at four-week intervals in conjunction with c-di-AMP used as adjuvant. Sera were collected from the animals 4 weeks after boost (day 56 (d56)) and used in an HAI assay against a panel of H1N1 (FIG.1A), H3N2 (FIG.1B), and Influenza B (IBV), (FIG.1C), influenza viruses. The virus strains are listed along the x-axes of the graphs in FIGs.1A-1C. The y-axes indicate the log2HAI titers for each vaccinated / immunized group and presents the titers as absolute mean values ± SEM. The dotted lines indicate HAI titers ranging from 1:40 (lower line) and 1:80 (upper line). In each of the bar couplets along the x-axis of the graphs, the bar representing immunization / vaccination with the pentavalent composition / vaccine, or a formulation thereof, composed of five COBRA HA and NA antigens as described herein (i.e., the pentavalent composition / vaccine containing influenza antigens “Y2” (H1 HA), “NG2” (H3 HA), “BC2” (IBV HA), “N1I” or “N1-I” (N1 NA), and “N2B” (N2 NA)) is shown on the left, and the bar representing pre-immune, mock-immunized animals is shown on the right. FIGs.2A-2C show graphs of serum neuraminidase inhibiting (NAI) antibody titers generated in pre-immune mice following vaccination. DBA / 2J mice (n=11) were previously infected with A / Singapore / 1986, A / Panama / 1999, and B / Hong Kong / 200142 days prior to vaccination. The mice were immunized / vaccinated intranasally with the pentavalent COBRA HA and NA antigen formulation as described in FIGs.1A-1C, twice at four-week intervals in conjunction with c-di-AMP used as adjuvant. Sera were collected from the animals 4 weeks after boost (d56) and used in a NAI assay against an N1 NA antigen (A / Brisbane / 2018 rNA strain), (FIG.2A) and an N2 NA antigen (A / Switzerland rNA strain), (FIG.2B). The sera were Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 diluted two-fold from a starting a dilution of 1:20 to quantify the NAI titer. Non-linear regression was conducted from these results to obtain reciprocal titer value that inhibited 50% of the NA activity (FIG.2C). FIGs.3A-3F provide graphs showing protective efficacy against seasonal virus infection in immunized / vaccinated mice. DBA / 2J mice were previously infected with A / Singapore / 1986, A / Panama / 1999, and B / Hong Kong / 2001 virus strains 42 days prior to immunization / vaccination. Mice were immunized / vaccinated intranasally with the pentavalent COBRA HA and NA antigen formulation described in the Examples above and herein twice at four-week intervals in conjunction with c-di-AMP used as adjuvant. Four weeks after the final immunization / vaccination, mice (n=11 per infection group) were intranasally infected with a lethal dose of A / Brisbane / 02 / 2018 (3×104PFU), (FIGs.3A and 3B), mouse-adapted A / Switzerland / 2013 (7×105PFU), (FIGs.3C and 3D), or B / Washington / 02 / 2019 (1×105PFU), (FIGs.3E and 3F). The animals were observed for clinical signs and their body weight was recorded daily post infection. Weight loss more than 25% was used as a primary measurement for determination of humane endpoint. FIGs.4A-4C present graphs demonstrating lung viral titers after seasonal challenge in immunized / vaccinated pre-immune mice. DBA / 2J mice were previously infected with A / Singapore / 1986, A / Panama / 1999, and B / Hong Kong / 2001 virus strains 42 days prior to immunization / vaccination. Mice were vaccinated intranasally with the pentavalent COBRA HA and NA antigen formulation described in the Examples above and herein twice at four-week intervals in conjunction with c-di-AMP used as adjuvant. Four weeks after final immunization / vaccination, mice were intranasally infected with a lethal dose of influenza virus A / Brisbane / 2018 (FIG.4A), mouse-adapted Switzerland / 2013 (FIG.4B), or B / Washington / 2019 (FIG.4C) and their lungs were excised on days 2 (n=3) and day 6 (n=3) post infection. Viral titers in lung tissues are presented as PFU / g on the y-axes. FIGs.5A-5C show bar graphs of serum HAI antibody titers generated in pre-immune ferrets after vaccination / immunization against seasonal influenza viruses. In brief, ferrets were previously infected with A / Singapore / 1986, A / Panama / 1999, and B / Hong Kong / 2001 strains of virus 60 days prior to vaccination. Ferrets were vaccinated / immunized with the pentavalent COBRA HA and NA antigen formulation (composition) containing 15 μg of each recombinant HA and NA antigen protein, or with the same pentavalent formulation (composition) in a high dose (HD), twice intranasally at four-week intervals in conjunction with c-di-AMP used as adjuvant. For the HD pentavalent formulation / composition, each of the recombinant H1, N1, and N2 HA and NA antigen proteins was used in an amount of 15 μg, except for the H3 NG2 Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 and IBV BC2 antigen proteins, which were used in an amount of 45 μg each. Sera were collected from the animals 4 weeks after boost (day 56 (d56)) and used in an HAI assay against a panel of H1N1 (FIG.5A), H3N2 (FIG.5B), and Influenza B (IBV), (FIG.5C), influenza viruses. The virus strains are listed along the x-axes of the graphs in FIGs.5A-5C. The y-axes indicate the log2 HAI titers for each vaccinated / immunized group and presents them as absolute mean values ± SEM. The dotted lines indicate HAI titers ranging from 1:40 (lower line) and 1:80 (upper line). In each of the bar triplets along the x-axis of the graphs, the bar representing immunization with the pentavalent HA and NA influenza antigen composition / vaccine formulation composed of five COBRA HA and NA antigens as described herein (i.e., the pentavalent composition / formulation containing influenza antigens “Y2” (H1 HA), “NG2” (H3 HA), “BC2” (IBV HA), “N1I” or “N1-I” (N1 NA), and “N2B” (N2 NA)) is shown on the left; the bar representing immunization with the high dose (HD) pentavalent HA and NA influenza antigen composition / vaccine formulation described herein is shown in the middle; and the bar representing mock-immunized animals is shown on the right. FIGs.6A-6D provide graphs and bar graphs showing serum NAI antibody titers generated in pre-immune ferrets following immunization / vaccination with the pentavalent COBRA HA and NA antigen-containing immunogen or following mock immunization. Ferrets were previously infected with A / Singapore / 1986, A / Panama / 1999, and B / Hong Kong / 2001 influenza virus strains 60 days prior to immunization / vaccination. Ferrets were immunized / vaccinated with the pentavalent COBRA HA and NA antigen formulation or with a pentavalent high dose (HD), in amounts as described for FIGs.5A-5C, intranasally twice at four- week intervals in conjunction with c-di-AMP used as adjuvant. Sera were collected from the animals 4 weeks after boost and were used in an NAI assay against the N1 (A / Brisbane / 2018 rNA) influenza virus strain (FIGs.6A and 6B) and against the N2 (A / Switzerland rNA) virus strain (FIGs.6C and 6D). The sera were diluted two-fold from a starting dilution of 1:20 to quantify the NAI titer. Non-linear regression was conducted from these results to obtain reciprocal titer that inhibited 50% of the NA activity (FIGs.6B and 6C) with GraphPad Prism 9 software (GraphPad, San Diego, CA, USA). FIGs.7A and 7B provide graphs showing body weight curves of immunized / vaccinated pre-immune ferrets following challenge with seasonal influenza virus strains. Ferrets were previously infected with A / Singapore / 1986, A / Panama / 1999, and B / Hong Kong / 2001 virus strains 60 days prior to immunization / vaccination. Ferrets were immunized / vaccinated with the described pentavalent COBRA HA and NA antigen formulation or a pentavalent high dose (HD) COBRA HA and NA formulation, as described for the above figures, intranasally twice at four- Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 week intervals in conjunction with c-di-AMP used as adjuvant. Four weeks after final the immunization / vaccination, the ferrets were intranasally infected with A / Brisbane / 02 / 2018 IAV influenza virus strain (108PFU), (FIG.7A), or with B / Washington / 02 / 2019 IBV influenza virus strain (107PFU), (FIG.7B), in a volume of 1 mL. The animals were observed for clinical signs of disease and their body weights were recorded daily post infection. FIGs.8A-8F provide bar graphs showing viral titers in the upper respiratory tract of ferrets following infection with seasonal influenza virus strains. Ferrets were previously infected with A / Singapore / 1986, A / Panama / 1999, and B / Hong Kong / 2001 virus strains 60 days prior to immunization / vaccination. The ferrets were immunized / vaccinated with the above-described pentavalent COBRA HA and NA antigen formulation or the pentavalent formulation at high dose (HD formulation) intranasally, twice, at four-week intervals in conjunction with c-di-AMP used as adjuvant. The vaccinated animal groups are indicated on the x-axis. Four weeks after the second immunization / vaccination, the groups were challenged with the IAV, H1N1 A / Brisbane / 02 / 2018 virus strain (top row, FIGs.8A-8C) or with the IBV B / Washington / 02 / 2019 virus strain (bottom row, FIGs.8D-8F). Each graph represents viral titers from nasal washes taken from the animals on the indicated day post infection, i.e., day 1, day 3, or day 5, as quantified by viral plaque assay. The viral titers in nasal washes from the ferrets are presented as PFU / mL shown on the y-axis. Each dot represents an individual ferret. FIG.9 provides a diagram of a ferret vaccine study. For the pre-immune vaccine groups, the ferrets were intranasally infected with A / California / 2009, A / Panama / 1999, and B / Hong Kong / 2001 at least 60 days prior to vaccination. On days 0 and 28, pre-immune and naïve groups were vaccinated intranasally with c-di-AMP as adjuvant. Sera were collected on days 0, 28, and 56. Ferrets were challenged with A / Brisbane / 02 / 2018 (H1N1), B / Washington / 02 / 2019 (IBV), or A / Vietnam / 1203 / 2004 (H5N1) on day 56. Ferrets were weighed and monitored for clinical signs daily. Nasal washes were taken on days 57, 59, 61, and 63. The term “Octavalent COBRA” refers to an octavalent influenza immunogen the 8 recombinant proteins Y4, NG3, N1I, N2A, BC3, Z1, IAN8, and Q6. FIGs.10A-10F provide bar graphs comparing total IgG antibody response before and after vaccination in ferrets. Ferrets were vaccinated intranasally twice at four-week intervals with c-di-AMP as adjuvant. Total IgG antibody titers were determined against each of the 8 COBRA components (i.e., Y4, NG3, N1I, N2A, BC3, Z1, IAN8, and Q6), as indicated on the x-axis, from sera collected before vaccination (d0, left) and after final vaccination (d56, right) from naïve ferrets given COBRA vaccination (FIGs.10A and 10B), pre-immune ferrets given COBRA vaccination (FIGs.10C and 10D), and pre-immune ferrets given mock vaccination (FIGs.10E Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 and 10F). Each dot represents an individual ferret. One-way ANOVA was used to analyze the statistical differences between d0 and d56 ELISA results for each group by GraphPad Prism 9 software (GraphPad, San Diego, CA, USA). A p value less than 0.05 was defined as statistically significant (*, p < 0.05; **, p < 0.01; ***, p < 0.001; ****, p < 0.0001). FIGs.11A-11C provide bar graphs comparing total stem IgG antibody response before and after vaccination in ferrets. Ferrets were vaccinated intranasally twice at four-week intervals with c-di-AMP as adjuvant. Total IgG antibody titers were determined against group 1 and group 2 stem proteins, as indicated on the x-axis, from sera collected before vaccination (d0, grey bar) and after final vaccination (d56, black bar) from (FIG.11A) naïve ferrets given COBRA vaccination, (FIG.11B) pre-immune ferrets given COBRA vaccination, and (FIG.11C) pre- immune ferrets given mock vaccination. Multiple unpaired t tests were used to analyze the statistical differences between d0 and d56 ELISA results for each group by GraphPad Prism 9 software (GraphPad, San Diego, CA, USA). A p value less than 0.05 was defined as statistically significant (*, p < 0.05; **, p < 0.01; ***, p < 0.001; ****, p < 0.0001; ns not significant). FIGs.12A-12F provide bar graphs showing serum hemagglutination inhibition (HAI) antibody titers for seasonal viruses before and after vaccination in ferrets. Ferrets were vaccinated with octavalent COBRA formulation (containing the octavalent influenza immunogen containing the 8 recombinant proteins Y4, NG3, N1I, N2A, BC3, Z1, IAN8, and Q6) intranasally twice at four-week intervals with c-di-AMP as adjuvant. Pre-immune ferrets were previously infected with A / California / 2009, A / Panama / 1999, and B / Hong Kong / 2001. Sera were collected before vaccination (left panels) and 4 weeks after second vaccination (right panels) for HAI assay against a panel of (FIGs.12A and 12B) H1N1, (FIGs.12C and 12D) H3N2 and (FIGs. 12E and 12F) Influenza B viruses. The virus strains are listed along the x-axis. The y-axis indicates the log2 HAI titers for each vaccinated group and presents them as absolute mean values ± standard error of mean (SEM). The dotted lines indicate HAI titers ranging from 1:40 (lower line) and 1:80 (upper line). Statistical differences between day 0 and day 56 HAI titers for each vaccine group were analyzed using two-way ANOVA with multiple comparisons by GraphPad Prism 9 software (GraphPad, San Diego, CA, USA). A p value of less than 0.05 was defined as statistically significant (*, p < 0.05; **, p < 0.01; ***, p < 0.001; ****, p < 0.0001). For each set of three bars in FIGs.12A-12F, the bars represent, in order from left-to-right, “Pre- immune COBRA,” “Naïve COBRA,” and “Pre-immune mock.” FIGs.13A and 13B provide bar graphs showing serum hemagglutination inhibition (HAI) antibody titers for pre-pandemic viruses before and after vaccination in ferrets. Ferrets were vaccinated with octavalent COBRA formulation (containing the octavalent influenza Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 immunogen containing the 8 recombinant proteins Y4, NG3, N1I, N2A, BC3, Z1, IAN8, and Q6) intranasally twice at four-week intervals with c-di-AMP as adjuvant. Pre-immune ferrets were previously infected with A / California / 2009, A / Panama / 1999, and B / Hong Kong / 2001. Sera were collected before vaccination (FIG.13A) and 4 weeks after second vaccination (FIG.13B) for HAI assay against a panel of pre-pandemic reassortant viruses. The virus strains are listed along the x-axis. The y-axis indicates the log2HAI titers for each vaccinated group and presents them as absolute mean values ± standard error of the mean (SEM). The dotted lines indicate HAI titers ranging from 1:40 (lower line) and 1:80 (upper line). Statistical differences between day 56 HAI titers for each vaccine group were analyzed using unpaired t-tests by GraphPad Prism 9 software (GraphPad, San Diego, CA, USA). A p value of less than 0.05 was defined as statistically significant (*, p < 0.05; ns, not significant). For each set of three bars in FIGs.13A and 13B, the bars represent, in order from left-to-right, “Pre-immune COBRA,” “Naïve COBRA,” and “Pre-immune mock.” FIG.14A-14F provide plots and bar graphs showing serum neuraminidase (NA) inhibition (NAI) antibody titers before and after vaccination in ferrets. Ferrets were vaccinated with octavalent COBRA formulation (containing the octavalent influenza immunogen containing the 8 recombinant proteins Y4, NG3, N1I, N2A, BC3, Z1, IAN8, and Q6) intranasally twice at four-week intervals with c-di-AMP as adjuvant. Pre-immune ferrets were previously infected with A / California / 2009, A / Panama / 1999, and B / Hong Kong / 2001. Sera were collected before vaccination (d0) and 4 weeks after second vaccination (d56) for NAI assay against (FIGs.14A, 14B, and 14C) N1 and (FIGs.14D, 14E, and 14F) N2 recombinant proteins. In FIGs.14C and 14F, statistical differences between dNAI50 titers were analyzed using one-way ANOVA with multiple comparisons GraphPad Prism 9 software (GraphPad, San Diego, CA, USA). A p value of less than 0.05 was defined as statistically significant (*, p < 0.05; **, p < 0.01; ***, p < 0.001; ****, p < 0.0001). FIGs.15A-15C provide plots showing body weight curve after seasonal or pandemic virus challenge in vaccinated ferrets. Ferrets were vaccinated intranasally twice at four-week intervals with c-di-AMP as adjuvant. Vaccine groups were as follows: pre-immune ferrets given octavalent COBRA recombinant HA and NA (“Pre-immune COBRA”), naïve ferrets given octavalent COBRA recombinant HA and NA (“Naïve COBRA”), pre-immune ferrets given mock vaccination (“Pre-immune mock”), or naïve ferrets given mock vaccination (“Naïve Mock”). Pre-immune ferrets were previously infected with A / California / 2009, A / Panama / 1999, and B / Hong Kong / 2001. Four weeks after final vaccination, ferrets were intranasally infected with (FIG.15A) A / Brisbane / 02 / 2018 (108PFU), (FIG.15B) B / Washington / 02 / 2019 (107PFU), Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 or a lethal dose of (FIG.15C) A / Vietnam / 1203 / 2004 (105PFU) in a volume of 1 mL. The animals were observed for clinical signs and their body weight was recorded daily post infection. FIGs.16A-16F provide bar graphs showing viral titers in upper respiratory tract of ferrets after seasonal infection. Ferrets were vaccinated intranasally twice at four-week intervals with c-di-AMP as adjuvant. Vaccine groups are indicated on x-axis. Four weeks after second vaccination, the groups were challenge with H1N1 A / Brisbane / 02 / 2018 (FIGs.16A-16C) or IBV B / Washington / 02 / 2019 (FIGs.16D-16F). Each figure represents viral titers from nasal washes taken on the indicate day post infection- day 1, day 3, or day, as quantified by viral plaque assay. Viral titers in nasal washes are presented as PFU / mL shown on the y-axis. Each dot represents an individual ferret. Statistical differences were analyzed by one-way ANOVA with multiple comparisons by GraphPad Prism 9 software (GraphPad, San Diego, CA, USA). A p value of less than 0.05 was defined as statistically significant (*, p < 0.05; **, p < 0.01; ***, p < 0.001; ****, p < 0.0001). FIGs.17A-17F provide plots showing total IgG antibody response before and after vaccination in ferrets. Ferrets were vaccinated intranasally twice at four-week intervals with c-di- AMP as adjuvant. Total IgG antibody titers were determined against each of the 8 COBRA components (i.e., H1, H3, H2, H5, H7, IBV, N1, and N2, as described in Table 4), as indicated on the x-axis, from sera collected before vaccination (d0, left) and after final vaccination (d56, right) from naïve ferrets given COBRA vaccination (FIGs.17A and 17B), pre-immune ferrets given COBRA vaccination (FIGs.17C and 17D), and pre-immune ferrets given mock vaccination (FIGs.17E and 17F). FIG.18 provides a plot showing an analysis of the kinetic IgG titer in sera (humoral immune response). H1N1-specific IgG titer was evaluated in sera by enzyme-linked immunosorbent assay (ELISA). Balb / c mice (n = 15) were vaccinated on days 0, 14 and 28 with the Octavalent COBRA-Mix (containing the octavalent influenza immunogen containing the 8 recombinant proteins Y4, NG3, N1I, N2A, BC3, Z1, IAN8, and Q6) alone (5 µg / dose) or co- administered with 10 μg / dose of c-di-AMP or Addavax (1:1) in a total volume of 30 - 50 μL per dose by intramuscular (i.m.) route. The negative control group received only PBS + c-di-AMP. Antigen-specific IgG titer were determined on day 0, 13, 27 and 49. The results are expressed as mean endpoint titers. FIG.19 provides a plot showing an analysis of the H1N1 hemagglutination inhibition titer (HAI) in sera. The reciprocal of the serum dilution represents the HAI titer of the respective serum. Negative samples were assigned an arbitrary titer of 5 for calculation purposes. Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 FIGs.20A-20C provide plots relating to H1N1 challenge of c-di-AMP adjuvanted octavalent COBRA-Mix vaccinated mice. FIG.20A provides a plot showing protection of mice vaccinated with the Octavalent COBRA-Mix (0.75, 1.5, 3 and 5 µg) in combination with c-di- AMP against influenza A virus infection by parenteral route. The octavalent COBRA-Mix contained equal mass amounts of each antigen. FIG.20B provides a plot showing development of weight (in %). FIG.20C provides a plot showing clinical symptoms after H1N1 challenge. The results of the health status are expressed as sum of all measured clinical symptoms with SEM. Vaccinated BALB / c mice were challenged with the influenza strain A / Puerto Rico / 8 / 34 (H1N1) on day 49. Survival rates were measured after challenge for a period of two weeks. FIG.21 provides a bar graph showing an analysis of the cellular immune response of COBRA-restimulated splenocytes, where the analysis was completed to assess cellular responses induced by vaccination. The number of IFN-γ, IL-2, IL-4, IL-10 and IL-17-producing cells was determined by enzyme-linked immunospot (ELISPOT) assay. Splenocytes from immunized groups of mice were incubated in the presence of H1N1 HA protein for 24 or 48 h, respectively. Untreated mice served as control reflecting the baseline stimulation capacity of H1N1 HA protein. Results are expressed as a number of spots of cells producing cytokines per 106splenocytes. The background values of unstimulated cells were subtracted. For each set of five bars in FIG.21, the bars represent, in order from left-to-right, IFNg, IL-2, IL-4, IL-17, and IL- 10. FIG.22 provides a bar graph showing an analysis of the systemic humoral immune response (IgG titer in sera) in mice. H1N1, H3N2 and H5N1 specific IgG titers were measured in mice vaccinated with PBS (control + c-di-AMP), or with the Octavalent COBRA-Mix (0.75 – 5 µg) alone or in combination with c-di-AMP or gold standard MPL (10 µg). The mice were vaccinated by the intranasal (i.n.) route. IgG titers were measured by enzyme-linked immunosorbent assay (ELISA). The results are expressed as mean endpoint titers with standard error of the mean (SEM). For each set of three bars in FIG.22, the bars represent, in order from left-to-right, H1N1, H3N2, and H5N1. FIG.23 provides a bar graph showing an analysis of the H1N1 hemagglutination inhibition titer (HAI) in sera from mice. The reciprocal of the serum dilution represents the HAI titer of the respective serum. Negative samples were assigned an arbitrary titer of 5 for calculation purposes. FIGs.24A-24C provide plots relating to H1N1 challenge of c-di-AMP adjuvanted octavalent COBRA-Mix vaccinated mice. Vaccinated BALB / c mice were challenged with the influenza strain A / Puerto Rico / 8 / 34 (H1N1) on day 49. Animals were monitored for a period of Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 two weeks after challenge. FIG.24A provides a plot showing protection of mice vaccinated with the Octavalent COBRA-Mix (0.75, 1.5, 3, 5 µg) in combination with c-di-AMP by intranasal (i.n.) route against influenza A virus infection. FIG.24B provides a plot showing development of weight (in %). FIG.24C provides a plot showing clinical symptoms of sub-lethal H1N1 challenge. The results of the health status, such as spontaneous and provoked behavior, physiological posture, fur and body weight development, are expressed as sum of all measured clinical symptoms with standard error of the mean (SEM) in mice showing alterations. FIG.25 provides a bar graph showing an analysis of the cellular immune response of COBRA-restimulated spleenocytes, where the analysis was completed to assess cellular responses induced by vaccination. The number of IFN-γ, IL-2, IL-4, IL-10 and IL-17-producing cells was determined by enzyme-linked immunospot (ELISPOT) assay. Splenocytes from immunized groups of mice were incubated in the presence of H1N1 HA protein for 24 or 48 h. Untreated mice served as control reflecting the baseline stimulation capacity of H1N1 HA protein. Results are expressed as a number of spots of cells producing cytokines per 106splenocytes. The background values of unstimulated cells were subtracted. For each set of five bars in FIG.25, the bars represent, in order from left-to-right, IFNg, IL-2, IL-4, IL-17, and IL- 10. DETAILED DESCRIPTION OF THE DISCLOSURE AND EMBODIMENTS Featured herein are pentavalent / octavalent immunogens, vaccines, or compositions composed of a combination of synthetic (non-naturally occurring), immunogenic antigens, e.g., protein and glycoprotein antigens, derived from the influenza (“flu”) hemagglutinin (HA) protein of influenza virus strains, e.g., H1, H2, H3, H5, H7, or IBV (influenza B virus), that elicit a potent, broadly reactive and long-lasting immune response in a subject. In an embodiment, the subject is a human subject. In an embodiment, the subject is a non-human subject. In an embodiment, the synthetic (non-naturally occurring), immunogenic antigen, e.g., protein and glycoprotein antigen, is derived from the virus neuraminidase (NA), e.g., N1 or N2, protein. Such immunogenic antigens are also referred to as “immunogens” herein. In an embodiment, the pentavalent / octavalent immunogen, vaccine, or composition described herein is composed of one or more polynucleotides encoding the five or eight influenza HA and / or NA antigen polypeptides of the pentavalent / octavalent immunogen, or vectors, virus particles, or delivery vehicles or agents containing the polynucleotides. The octavalent immunogens, or vaccines, include the antigens Y4, NG3, N1I, N2A, BC3 or BC2, Z1, IAN8, and Q6. The pentavalent immunogens, or vaccines include the antigens Y2, NG2, BC2, N1-I, and N2-B. Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 Development of next generation influenza virus vaccines is crucial to improve protection against circulating and emerging viruses. Current vaccine formulations have to be updated annually due to mutations in seasonal strains and do not offer protection against strains with pandemic potential. The present disclosure is based, at least in part, upon the use of a computationally optimized broadly reactive antigen (COBRA) methodology to generate broadly reactive immunogens for individual influenza subtypes, which elicit protective immune responses against a broad range of strains over numerous seasons. Octavalent / pentavalent mixtures of COBRA hemagglutinin (HA) (H1, H2, H3, H5, H7, and / or IBV) plus neuraminidase (NA) (N1 and / or N2) recombinant proteins mixed with c-di-AMP adjuvant were administered intranasally to naive or pre-immune ferrets in prime-boost fashion. Four weeks after final vaccination, collected sera were analyzed for breadth of antibody response and the animals were challenged with seasonal or pre-pandemic strains. The octavalent / pentavalent COBRA vaccine elicited antibodies that recognized a broad panel of strains representing different subtypes and these vaccinated animals were protected against influenza virus challenges. This demonstrated that the mixture of 5 or 8 COBRA HA / NA proteins (e.g., Y2, NG2, N2-B, Y4, NG3, N1I (N1-I), N2A, BC3 or BC2, Z1, IAN8, and / or Q6) mixed with an intranasal adjuvant is a promising candidate for a universal influenza vaccine (see, e.g., Table 4). The pentavalent immunogen or vaccine as described and used herein is composed of the following five influenza hemagglutinin (HA) and neuraminidase (NA) protein antigens: Y2 HA antigen (H1 influenza strain); NG2 HA antigen (H3 influenza strain); BC2 HA antigen (influenza B virus (IBV)); N1-I Neuraminidase (NA) antigen (N1 influenza); N2-B neuraminidase (NA) antigen (N2 NA). In an embodiment, the sequences were generated using COBRA or next-generation COBRA methodology as described in Example 10 herein. In embodiments, the HA and NA protein antigens are recombinant and / or recombinantly produced. Provided are broadly reactive pentavalent / octavalent immunogens that protect against disease caused by the influenza strains, such as H1, H2, H3, H5, H7, and IBV, as well as N1 and N2. In an embodiment, fully synthetic protein antigens are featured, such as influenza virus HA and NA protein antigens. Such HA and NA antigens are synthetic proteins not found in nature, yet they retain all of the functions of a natural influenza virus HA protein and are immunogenic, i.e., they can elicit an immune response, in particular, a broadly active immune response in the form of neutralizing antibodies and / or reactive T lymphocytes, following administration or delivery to, or introduction into, a subject, especially for influenza virus antigen immunogens. Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 Also provided are immunogenic compositions, e.g., vaccines, comprising the synthetic virus protein antigens, or nucleic acids encoding the antigens. HA and / or NA amino acid sequences and protein antigens having such sequences are particularly advantageous for use as immunogens, or in an immunogenic composition, e.g., a vaccine, which elicits a broadly reactive immune response in a subject, particularly a human subject, to whom the composition, or vaccine, is administered. The synthetic antigens are designed to generate a broadly active immune response, particularly in the form of neutralizing antibodies, along with a cellular immune response in some cases, in a subject. In an embodiment, the subject is a human subject. Such antigens are beneficial as immunogens, which elicit an immune response (e.g., production of neutralizing antibodies and / or a cellular immune response) against the virus, in particular, in cases in which more than one strain of virus co- circulate at a given time. By way of example, the broadly reactive influenza immunogenic antigens can be derived from influenza virus that frequently mutates parts of its genome to escape immune pressure, and as a consequence, evades immune surveillance in a subject whose immune system is not primed or stimulated to generate antibodies against antigenic epitopes (determinants) on the virus antigens following infection. Thus, the synthetic influenza virus antigens, e.g., H1, H2, H3, H5, H7, and IBV HA antigens and N1 or N2 NA antigens, comprise amino acid (or polynucleotide) sequences that will elicit greater numbers of neutralizing antibodies (and / or an improved cellular immune response) against potential influenza virus variants exhibiting antigenic drift compared with wild-type antigen sequences. In aspects, HA and / or NA immunogenic proteins, or immunogens of H1, H2, H3, H5, H7, IBV, N1 and / or N2 as described herein are employed in pentavalent / octavalent immunogenic vaccine compositions or formulations that may afford protection against many virus strains, e.g., seasonal virus strains, over time. The broadly reactive virus antigen immunogens and vaccines described herein are advantageous in that they are designed to provide broader and longer-lasting protection against several different viral (e.g., influenza virus) strains (or clades), such as those arising in different areas. The immunogenic influenza virus HA and / or NA antigens described herein are contained in a pentavalent / octavalent immunogenic composition (e.g., a pentavalent / octavalent vaccine) that can afford protective immunity against disease and pathology associated with influenza virus infection in a subject. The protective immunity is provided in the subject through the elicitation of broadly reactive, anti-HA and / or anti-NA specific antibody or cellular immune responses that protect the subject against virus strains that may have mutated or experienced antigenic drift. Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 Recombinant proteins are a promising alternative to the split-inactivated or attenuated influenza virus vaccines that are the industry standard. Recombinant protein vaccines have similar vaccine effectiveness in healthy adults and increased effectiveness in the elderly or immunocompromised. In addition, recombinant protein vaccines provide better protection against influenza-related hospitalization compared to split-inactivated vaccines in women and younger adults, in general, and in people without any high-risk conditions (Zimmerman, R.K. et al., Vaccine, 2023.41(35):5134-5140). Repeated recombinant protein administrations or vaccinations redirect antibody responses to effective epitopes and away from egg-adapted mutations, since most current vaccines are produced in embryonated chicken eggs, which reduces the antigenicity and effectiveness of the vaccine (Liu, F. et al., Nature Communications, 2024.15(1):254). Computationally optimized broadly reactive antigen (COBRA) methodology and next- generation COBRA technology and methods align and analyze multiple consensus sequences from thousands of virus isolates to generate a final immunogen that stimulates cross-protective immune responses against a large panel of strains for each subtype (Sautto, G.A. et al., Virology, 2018.15(1):1-12; Huang, Y., et al., Vaccines, 2021.9(7):793; WO 2020 / 014675; WO 2020 / 014673). As described herein, in order to expand the coverage of elicited immune responses to pre-pandemic and IBV strains, a multivalent immunogen (composition / vaccine) composed of different HA and NA proteins from among H1, H2, H3, H5, H7, and IBV COBRA HA proteins and N1, N2 COBRA NA proteins was developed and tested in both immunologically naive mice and in mice pre-immune to historical influenza viruses, and in both immunologically naive ferrets and ferrets pre-immune to historical influenza viruses. These immunogens (vaccines) were administered intranasally following admixture with the STING activator, bis-(3,5)-cyclic dimeric adenosine monophosphate (c-di-AMP) that is a strong stimulator of mucosal immune responses (Ebensen, T. et al., Vaccine, 2011.29(32): p.5210- 5220). The multivalent COBRA HA / NA-based immunogen (vaccine) elicited protective immune responses against seasonal influenza viruses. In particular, pentavalent / octavalent mixtures of COBRA hemagglutinin (HA) (H1, H2, H3, H5, H7, and IBV) and neuraminidase (NA) (N1 and N2) recombinant protein antigens in conjunction with a cyclic dinucleotide adjuvant, e.g., c-di-AMP adjuvant, were administered intranasally to naive or pre-immune mice or ferrets in prime-boost fashion (See, e.g., the Examples provided herein). Four weeks after final immunization (vaccination), sera were collected and analyzed for the breadth of immune response and antibody production elicited in the animals, and the animals were challenged with seasonal or pre-pandemic influenza virus Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 strains. As described, the multivalent immunogen / vaccine elicited antibodies in the animals. These elicited antibodies recognized and bound to a broad panel of strains representing different influenza virus subtypes. In addition, the vaccinated animals were protected against influenza virus challenges. Overall, and without wishing to be limiting, the multivalent mixture of five or eight different HA and / or NA influenza virus protein antigens in conjunction with an intranasal adjuvant serves as a promising candidate for a universal influenza vaccine. Most licensed influenza vaccines are delivered intramuscularly, which elicits systemic immune responses, but not local mucosal immune responses. Intranasal vaccine delivery can elicit robust humoral and cellular responses not only at systemic levels, but also at the site of influenza virus infection. This can, in turn, be instrumental for reducing virus infection and reducing horizontal transmission to susceptible hosts. Intranasal delivery has practical advantages over intramuscular delivery with increased patient compliance, ease of administration, and reduced sanitary costs. In an embodiment, virus antigen immunogens and vaccines as described herein are formulated with adjuvants for delivery to mucosal surfaces in order to overcome tolerogenic immune response and degradation. Influenza viruses The development of next generation influenza virus immunogens (vaccines) is crucial for improving protection against circulating and emerging flu viruses. Current vaccine formulations have to be updated annually due to mutations in seasonal strains and do not offer protection against strains with pandemic potential. Computationally optimized broadly reactive antigen (COBRA) methodology and next-generation versions of the COBRA methodology have been utilized to generate broadly-reactive immunogens for individual influenza subtypes, which elicit protective immune responses against a broad range of strains over numerous seasons. (See, for example, WO 2020 / 014675; WO 2020 / 014673). Influenza viruses, which are segmented negative-strand RNA viruses that belong to the Orthomyxoviridae family, cause severe respiratory disease in millions of people, resulting in severe morbidity and mortality each year (Iuliano, A.D. et al., The Lancet, 2018.391(10127): p. 1285-1300; Krammer, F., Nature Reviews Immunology, 2019.19(6): p.383-397). There are three types of influenza viruses that infect humans, namely, A, B, and C (IAV, IBV, and ICV), respectively). IAV is divided into two phylogenetic groups, group 1 and group 2 (Joyce, M.G. et al., Cell, 2016.166(3): p.609-623), and is further distinguished into subtypes identified by the hemagglutinin (HA) and neuraminidase (NA) surface glycoproteins. Currently there are 18 identified HA proteins (H1-H18) and 11 identified NA proteins (N1-N11). IBV is classified into Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 two lineages: Yamagata-like and Victoria-like (Krammer, F. et al., Nature Reviews: Disease Primers, 2018.4(1): p.3). H1N1 and H3N2 IAV and IBV strains circulate in humans, while avian strains of the H2, H5, and H7 subtypes have pandemic potential if transmitted from animal reservoirs to humans (Krammer, F. and P. Palese, Nature reviews Drug discovery, 2015.14(3): p.167-182). Influenza A viruses infect a wide variety of birds and mammals, including humans, horses, marine mammals, pigs, ferrets, and chickens. In animals, most influenza A viruses cause mild localized infections of the respiratory and intestinal tract. However, highly pathogenic influenza A strains, such as, for example, the H1N1 (“H1”) or H5N1 (“H5’”), or H7, or H9 strains cause systemic infections in poultry in which mortality may reach 100%. Animals infected with influenza A often act as a reservoir for the influenza viruses and certain subtypes have been shown to cross the species barrier to humans in whom they can cause severe disease and devastating flu outbreaks that can lead to death of the infected human subjects. There are three types of Influenza viruses that infect humans: A (IAV), B (IBV), and C (ICV). IAV is divided into two phylogenetic groups, group 1 and group 2, and further distinguished into subtypes identified by the hemagglutinin (HA) and neuraminidase (NA) surface glycoproteins. Currently there are 18 identified HA proteins (H1-H18) and 11 identified NA proteins (N1-N11). IBV is classified into two lineages: Yamagata-like and Victoria-like. H1N1 and H3N2 IAV and IBV strains circulate in humans, whereas avian strains of the H2, H5, and H7 subtype have pandemic potential if transmitted from animal reservoirs to humans. Influenza A viruses can be classified into subtypes based on allelic variations in antigenic regions of two genes that encode surface glycoproteins, namely, hemagglutinin (HA) and neuraminidase (NA) which are required for viral attachment and cellular release, respectively. Currently, sixteen subtypes of HA (H1-H16) and nine NA (N1-N9) antigenic variants are known for influenza A virus. Previously, only three subtypes were known to circulate in humans (H1N1 or H1N2). However, in recent years, for example, the pathogenic H5N1 subtype of avian influenza A has been reported to cross the species barrier and infect humans as documented in Hong Kong in 1997 and 2003, leading to the death of several patients. In humans, the avian influenza virus infects cells of the respiratory tract as well as the intestinal tract, liver, spleen, kidneys and other organs. Symptoms of avian influenza infection include fever, respiratory difficulties, including shortness of breath and cough, lymphopenia, diarrhea and difficulties regulating blood sugar levels. In contrast to seasonal influenza, the group most at risk is healthy adults which make up the bulk of the population. Due to the high pathogenicity of certain avian influenza A subtypes, particularly H5N1, and their demonstrated Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 ability to cross over to infect humans, there is a significant economic and public health risk associated with these viral strains, including a real epidemic and pandemic threat. Currently, no effective vaccines for H5N1 infection are available. The influenza A virus genome encodes nine structural proteins and one nonstructural (NS1) protein with regulatory functions. The influenza virus segmented genome contains eight negative-sense RNA (nsRNA) gene segments (PB2, PB1, PA, NP, M, NS, HA and NA) that encode at least ten polypeptides, including RNA-directed RNA polymerase proteins (PB2, PB 1 and PA), nucleoprotein (NP), neuraminidase (NA), hemagglutinin, e.g., subunits HA1, frequently referred to as the “head” subunit; and HA2, frequently referred to as the “tail” or “stalk” subunit; the matrix proteins (M1 and M2); and the non-structural proteins (NS1 and NS2) (See, e.g., Krug et al., 1989, In: The Influenza Viruses, R. M. Krug, ed., Plenum Press, N.Y., pp. 89152). The ability of influenza virus to cause widespread disease is due to its ability to evade the immune system by undergoing antigenic change, which is believed to occur when a host is infected simultaneously with both an animal influenza virus and a human influenza virus. During mutation and reassortment in the host, the virus may incorporate an HA and / or NA surface protein gene from another virus into its genome, thereby producing a new influenza subtype and evading the immune system. Because of antigenic variation (drift) in the circulating strains of influenza viruses, in particular, in the HA and NA proteins of the virus, the efficacy of immunogenic compositions, e.g., vaccines, against influenza virus has frequently been less than optimal and sub-par. The methods described herein provide a pentavalent composition of broadly reactive HA and NA antigens (recombinant antigens) that generate a broadly reactive immune response, particularly, in the form of neutralizing antibodies that bind to the viral antigens and neutralize the activity of the virus (e.g., its ability to infect cells), to treat influenza and its symptoms more effectively. Influenza Virus Hemagglutinin (HA) and Neuraminidase (NA) Proteins HA is a viral surface glycoprotein that generally comprises approximately 560 amino acids (e.g., 566 amino acids) and represents 25% of the total virus protein. As described herein, HA is a protein antigen that is highly useful as an immunogen because it contains a diverse repertoire of epitopes against which antibodies are generated in a subject or host that encounters the HA antigen of influenza viruses during infection. HA is responsible for adhesion of the viral particle to, and its penetration into, a host cell, particularly, in the respiratory epithelium, in the early stages of infection. Cleavage of the virus Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 HA0 precursor into the HA1 and HA2 sub-fragments is a necessary step for the virus to infect a cell. Thus, cleavage is required to convert new virus particles in a host cell into virions capable of infecting new cells. Cleavage is known to occur during transport of the integral HA0 membrane protein from the endoplasmic reticulum of the infected cell to the plasma membrane. During transport, HA undergoes a series of co- and post-translational modifications, including proteolytic cleavage of the precursor HA into the amino-terminal fragment HA1 (“head”) and the carboxy terminal HA2 (“tail” or “stalk”). One of the primary difficulties in growing influenza strains in primary tissue culture or established cell lines arises from the requirement for proteolytic cleavage activation of the influenza hemagglutinin in the host cell. Although it is known that an uncleaved HA can mediate attachment of the virus to its neuraminic acid-containing receptors on a cell surface, it is not capable of the next step in the infectious cycle, which is fusion. It has been reported that exposure of the hydrophobic amino terminus of HA2 by cleavage is required so that it can be inserted into the target cell, thereby forming a bridge between the virus and the target cell membranes. This process is followed by fusion of the two membranes and entry of the virus into the target cell. Proteolytic activation of HA involves cleavage at an arginine residue by a trypsin-like endoprotease, which is often an intracellular enzyme that is calcium-dependent and has a neutral pH optimum. Since the activating proteases are cellular enzymes, the infected cell type determines whether the HA is cleaved. The HA of the mammalian influenza viruses and the nonpathogenic avian influenza viruses are susceptible to proteolytic cleavage only in a restricted number of cell types. On the other hand, HA of pathogenic avian viruses among the H5 and H7 subtypes are cleaved by proteases present in a broad range of different host cells. Thus, there are differences in host range resulting from differences in hemagglutinin cleavability which are correlated with the pathogenic properties of the virus. Neuraminidase (NA) is a second membrane glycoprotein of the influenza viruses. The presence of viral NA has been shown to be important for generating a multi-faceted protective immune response against an infecting virus. For most influenza A viruses, NA is 413 amino acids in length and is encoded by a gene of 1413 nucleotides. Nine different NA subtypes have been identified in influenza viruses (N1, N2, N3, N4, N5, N6, N7, N8 and N9), all of which have been found among wild birds. NA is involved in the destruction of the cellular receptor for the viral HA by cleaving terminal neuraminic acid (also called sialic acid) residues from carbohydrate moieties on the surfaces of infected cells. NA also cleaves sialic acid residues from viral proteins, preventing aggregation of viruses. Using this mechanism, it is hypothesized that NA facilitates the release of viral progeny by preventing newly formed viral particles from Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 accumulating along the cell membrane, as well as by promoting transportation of the virus through the mucus present on the mucosal surface. NA is an important antigenic determinant that is subject to antigenic variation. In addition to the surface proteins HA and NA, influenza virus comprises six additional internal genes, which give rise to eight different proteins, including polymerase genes PB1, PB2 and PA, matrix proteins M1 and M2, nucleoprotein (NP), and non-structural proteins NS1 and NS2 (See, e.g., Horimoto et al., 2001, Clin Microbiol Rev.14(1):129-149). For packaging into progeny virions, viral RNA is transported from the nucleus as a ribonucleoprotein (RNP) complex composed of the three influenza virus polymerase proteins, the nucleoprotein (NP), and the viral RNA, in association with the influenza virus matrix 1 (M1) protein and nuclear export protein (Marsh et al., 2008, J Virol, 82:2295-2304). The M1 protein that lies within the envelope is thought to function in assembly and budding. A limited number of M2 proteins are integrated into the virions (Zebedee, 1988, J. Virol.62:2762-2772). These M2 proteins form tetramers having H+ ion channel activity, and when activated by the low pH in endosomes, acidify the inside of the virion, thus facilitating its uncoating (Pinto et al., 1992, Cell 69:517-528). Amantadine is an anti-influenza drug that prevents viral infection by interfering with M2 ion channel activity, thus inhibiting virus uncoating. NS1, a nonstructural protein, has multiple functions, including regulation of splicing and nuclear export of cellular mRNAs as well as stimulation of translation. The major function of NS1 seems to be to counteract the interferon activity of the host, since an NS1 knockout virus was viable, although it grew less efficiently than the parent virus in interferon-nondefective cells (Garcia-Sastre, 1998, Virology 252:324-330). The NS2 nonstructural protein has been detected in virus particles (Richardson et al., 1991, Arch. Virol.116:69-80; Yasuda et al., 1993, Virology 196:249-255). The average number of NS2 proteins in a virus particle was estimated to be 130-200 molecules. An in vitro binding assay has demonstrated direct protein-protein contact between M1 and NS2. NS2-M1 complexes have also been detected by immunoprecipitation in virus-infected cell lysates. The NS2 protein is thought to play a role in the export of the RNP from the nucleus through interaction with M1 protein (Ward et al., 1995, Arch. Virol.140:2067-2073). Viral Proteins and Virus-Like Particles (VLPs) Provided and described are non-naturally occurring, broadly reactive influenza (e.g., H1, H2, H3, H5, H7, or IBV) HA immunogenic polypeptides (immunogens) and virus-like particles (VLPs) comprising an influenza virus HA immunogen containing diverse epitopes (antigenic Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 determinants) that endow the HA antigen with the ability to generate a broadly active immune response against influenza and its symptoms, either prophylactic or therapeutic, following administration and delivery to a susceptible subject. In particular embodiments, the broadly reactive HA or NA polypeptides of the disclosure are administered as part of a VLP. The pentavalent / octavalent compositions / vaccines and formulations thereof as described herein contain five or eight different HA and NA influenza virus antigens that are isolated, non- naturally occurring, broadly reactive influenza (e.g., H1, H2, H3, H5, H7, and IBV) HA and NA immunogenic antigen proteins (immunogens), as well as virus-like particles (VLPs) comprising the pentavalent / octavalent composition / vaccine components. In an embodiment, the HA and NA antigen proteins are recombinant proteins (polypeptides) and / or are recombinantly produced. The influenza virus HA and NA protein antigens of the pentavalent / octavalent composition / vaccine provide a immunogen or immunogenic composition which contains diverse epitopes (antigenic determinants) that endow the HA and NA antigen components of the pentavalent / octavalent composition / vaccine with diverse epitopes against which a broadly reactive immune response against influenza virus, and against disease caused by influenza virus infection and symptoms thereof, is generated in a subject, e.g., a human or non-human mammal. Such an immune response may be either prophylactic or therapeutic, following administration and delivery of the pentavalent / octavalent composition / vaccine to a susceptible, responsive subject. The pentavalent / octavalent composition / vaccine, or a formulation thereof, as described herein contains a mixture of isolated, immunogenic HA and NA virus protein antigens having amino acid sequences as set forth in, for example, SEQ ID NO: 1 (Y2 (H1 HA)), SEQ ID NO: 2 (NG2 (H3 HA)), SEQ ID NO: 3 (BC2 (IBV HA)), SEQ ID NO: 4 (N1-I (N1 NA)), SEQ ID NO: 5 (N2-B (N2 NA)), SEQ ID NO: 51 (Y4 (H1 HA)), SEQ ID NO: 40 (NG3 (H3 HA)), SEQ ID NO: 65 (N2A (N2 NA)), SEQ ID NO: 69 (BC3 (IBV HA)), SEQ ID NO: 56 (Z1 (H2 HA)), SEQ ID NO: 34 (IAN8 (H5 HA)), and SEQ ID NO: 45 (Q6 (H7 HA)). In an embodiment, a delivery vector or construct, e.g., a mammalian expression vector or construct or a nucleic acid, such as mRNA, as delivery agent, contains polynucleotide sequences encoding the full-length HA and NA virus protein antigens. In an embodiment, soluble forms of the isolated, immunogenic HA and NA virus protein antigens are contained in the pentavalent / octavalent composition / vaccine, or a formulation thereof, e.g., having amino acid sequences as set forth in, for example, SEQ ID NO: 6 (sY2 (H1 HA)), SEQ ID NO: 7 (sNG2 (H3 HA)), SEQ ID NO: 8 (sBC2 (IBV HA)), SEQ ID NO: 9 (sN1-I (N1 NA)), SEQ ID NO: 10 (sN2-B (N2 NA)), SEQ ID NO: 53 (sY4 (sH1 HA)), SEQ ID NO: 42 (sNG3 (sH3 HA)), SEQ ID NO: 62 (sN1I (sN1 NA)), SEQ ID NO: 67 (sN2A (sN2 NA)), SEQ ID NO: 71 (sBC3 (sIBV HA)), SEQ ID NO: 58 (sZ1 (sH2 HA)), SEQ Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 ID NO: 36 (sIAN8 (sH5 HA)), and SEQ ID NO: 47 (sQ6 (sH7 HA)). In other embodiments, the pentavalent / octavalent composition / vaccine, or a formulation thereof, containing the mixture of five or eight, isolated, non-naturally occurring HA and NA influenza virus protein antigens are administered as part of a VLP. It will be understood that the pentavalent / octavalent composition / vaccine, or a formulation thereof, containing the five or eight, isolated influenza virus HA and NA immunogens and sequences as described and provided herein are non-naturally occurring and generate an immune response, such as an antibody immune response that is broadly reactive against a number of diverse virus strains or subtypes, and against the HA and NA antigen proteins from a number of diverse virus strains and subtypes, whether or not these characteristics and features are explicitly stated. It will be further understood that the antigen proteins contained in the pentavalent / octavalent composition / vaccine, or a formulation thereof, as described herein and used as immunogens / vaccines are isolated, non-naturally occurring or synthetic antigens that elicit an immune response, e.g., neutralizing antibodies and / or a cellular immune response, in a subject following administration, e.g., in the form of immunization / vaccination. The influenza VLPs include the viral HA and NA. In an embodiment, an M1 protein is included. The production of influenza VLPs has been described in the art and is within the skill and expertise of one of ordinary skill in the art. Briefly, and as described, influenza VLPs can be produced by transfection of host cells with one or more plasmids containing polynucleotide sequences that encode the pentavalent / octavalent composition / vaccine composed of the HA and NA as described herein. After incubation of the transfected cells for an appropriate time to allow for protein expression (such as for approximately 72 hours), VLPs can be isolated from cell culture supernatants. Influenza VLPs can be purified from cell supernatants using procedures practiced in the art, for example, VLPs can isolated by low speed centrifugation (to remove cell debris), vacuum filtration and ultracentrifugation through 20% glycerol. In an embodiment, VLPs containing the pentavalent / octavalent composition / vaccine can be produced, isolated and used as immunogens or in immunogenic compositions. The influenza VLPs can be used as influenza vaccines to elicit an immune response against the different influenza virus strains, such as H1, H2, H3, H5, H7, and IBV influenza viruses. In particular, the component, broadly reactive influenza HA and NA polypeptide antigens of the pentavalent / octavalent composition / vaccine (or VLPs) contain antigenic determinants that are broadly reactive and serve to elicit an immune response in a subject (e.g., the production of neutralizing antibodies and / or activated T-cells) that can treat a virus-infected Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 subject (e.g., neutralize the infecting virus) and / or protect a subject against full-blown virus infection, associated diseases, and / or the signs and symptoms thereof. In an embodiment, the antigen sequences of the broadly reactive and immunogenic HA and NA influenza antigens of the pentavalent / octavalent composition / vaccine as described herein contain a diverse repertoire of epitopic determinants that can reflect antigenic drift and sequence variability in the antigenic proteins of influenza viruses. In particular, an influenza virus HA and NA antigen as described herein can comprise an amino acid sequence that contains antigenic determinants (epitopes) derived from sequence diverse influenza virus strains, including drift variants, against which broadly reactive neutralizing antibodies and a T-cell response can be raised, especially when the antigen is used as an immunogenic product, (an immunogen), e.g., an antiviral vaccine, that is introduced into a subject. Because the broadly reactive influenza HA and NA antigens and the sequences thereof in the pentavalent / octavalent composition / vaccine as described herein and used as an immunogen or immunogenic composition elicit a broadly reactive immune response in an immunocompetent subject, the pentavalent / octavalent composition / vaccine provides a superior immunogenic product (e.g., a vaccine) that captures the antigenic determinants of different influenza isolates (subtypes or strains), against which broadly active immune responses (e.g., broadly active neutralizing antibodies and / or cellular immune responses) are generated. It is noted that the terms “broadly active” and “broadly reactive” are used synonymously herein. In an embodiment, the influenza virus antigens that are included in the pentavalent / octavalent composition / vaccine as described herein are HA and NA protein, polypeptide or peptide antigens of influenza virus which currently cause disease or infection and its symptoms, such as influenza, flu, or infectious bronchitis. In another embodiment, the influenza virus HA and NA antigens that are included in the pentavalent / octavalent composition / vaccine as described herein are polypeptide or peptide antigens which may cause future disease and infection. In an embodiment, the influenza virus antigens that are included in the pentavalent / octavalent composition / vaccine as described herein are polynucleotide sequences encoding the HA and NA antigens. The five or eight, broadly reactive influenza virus HA and NA immunogenic protein and nucleic acid sequences included in the pentavalent / octavalent composition / vaccine are described herein, e.g., SEQ ID NO: 51 (Y4 (H1 HA)), SEQ ID NO: 40 (NG3 (H3 HA)), SEQ ID NO: 65 (N2A (N2 NA)), SEQ ID NO: 69 (BC3 (IBV HA)), SEQ ID NO: 56 (Z1 (H2 HA)), SEQ ID NO: 34 (IAN8 (H5 HA)), SEQ ID NO: 45 (Q6 (H7 HA)), amino acid SEQ ID NO: 1 of “Y2”, a full length HA antigen protein of an H1 influenza virus strain (“Y2 (H1 HA)” herein), amino acid SEQ ID NO: 2 of “NG2”, a full length HA antigen protein Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 of an H3 influenza virus strain (“NG2 (H3 HA)” herein), amino acid SEQ ID NO: 3 of “BC2”, a full length HA antigen protein of influenza B virus (IBV) (“BC2 (IBV HA)” herein), amino acid SEQ ID NO: 4 of “N1-I”, a full length neuraminidase (NA) N1 antigen protein (“N1-I (N1 NA)” herein), and amino acid SEQ ID NO: 5 of “N2-B”, a full length N2 NA antigen protein (“N2-B (N2 NA)” herein). Soluble amino acid protein sequences of these HA and NA antigens are also provided, e.g., SEQ ID NO: 53 (sY4 (sH1 HA)), SEQ ID NO: 42 (sNG3 (sH3 HA)), SEQ ID NO: 62 (sN1I (sN1 NA)), SEQ ID NO: 67 (sN2A (sN2 NA)), SEQ ID NO: 71 (sBC3 (sIBV HA)), SEQ ID NO: 58 (sZ1 (sH2 HA)), SEQ ID NO: 36 (sIAN8 (sH5 HA)), and SEQ ID NO: 47 (sQ6 (sH7 HA)), SEQ ID NO: 6 (soluble Y2 amino acid sequence (“sY2”)), SEQ ID NO: 7 (soluble NG2 amino acid sequence (“sNG2”)), SEQ ID NO: 8 (soluble BC2 amino acid sequence (“sBC2”)), SEQ ID NO: 9 (soluble N1-I amino acid sequence (“sN1-I”)), and SEQ ID NO: 10 (soluble N2-B amino acid sequence (“sN2-B”)). SEQ ID NO: 11 (sY2), SEQ ID NO: 12 (sNG2), SEQ ID NO: 13 (sBC2), SEQ ID NO: 14 (sN1-I), SEQ ID NO: 15 (sN2-B), and SEQ ID NOs: 68, 37, 43, 48, 54, 59, 63, 72, and 13 designate nucleic acid sequences encoding the soluble HA and NA antigen proteins as described; and SEQ ID NO: 16 (FL Y2); SEQ ID NO: 17 (FL NG2); SEQ ID NO: 18 (FL BC2), SEQ ID NO: 19 (FL N1-I), SEQ ID NO: 20 (FL N2-B), SEQ ID NO: 66, SEQ ID NO: 35, SEQ ID NO: 41, SEQ ID NO: 46, SEQ ID NO: 52, SEQ ID NO: 57, SEQ ID NO: 19, SEQ ID NO: 70, and SEQ ID NO: 18 designate nucleic acid sequences encoding the full length HA and NA antigen proteins as described. In another embodiment, the influenza HA and NA sequences of the pentavalent / octavalent composition / vaccine described herein are expressed in a cell as a polypeptide, protein, or peptide. In an embodiment, the immunogenic influenza HA and NA sequences of the pentavalent / octavalent composition / vaccine described herein are isolated and / or purified. In an embodiment, the pentavalent / octavalent composition / vaccine composed of the immunogenic influenza HA and NA sequences as described herein is formulated for administration to a subject in need. In an embodiment, the pentavalent / octavalent composition / vaccine is administered to a subject in need thereof in an effective amount to elicit an immune response in the subject. In an embodiment, the immune response elicits neutralizing antibodies. In an embodiment, a cellular immune response is elicited. In an embodiment, the immune response is prophylactic or therapeutic. In an embodiment, the pentavalent / octavalent composition / vaccine containing the five or eight, isolated, non-naturally occurring influenza virus antigen proteins as immunogens (immunogenic sequences) is provided that elicits a broadly reactive immune response in a subject following introduction, administration, or delivery of the immunogen to the subject. The Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 route of introduction, administration, or delivery is not limited and may include, for example, intravenous, subcutaneous, intramuscular, oral, intranasal, and mucosal routes, etc. In a specific embodiment, the pentavalent / octavalent composition / vaccine, or a formulation thereof, is administered intranasally, and the formulation comprises an adjuvant, such as c-di-AMP. The pentavalent / octavalent composition / vaccine may be therapeutic (e.g., administered to a subject following a symptom of disease (e.g., flu or bronchitis) caused by or associated with influenza virus infection, or it may be prophylactic (protective), (e.g., administered to a subject prior to the subject having or expressing a symptom of disease (e.g., flu or bronchitis), or full-blown disease, caused by influenza virus. In an embodiment, the final amino acid sequence of the HA and NA antigen proteins contained in the pentavalent / octavalent composition / vaccine is reverse translated and optimized for expression in mammalian cells. As will be appreciated by the skilled practitioner in the art, optimization of the nucleic acid sequence includes optimization of the codons for expression of a sequence in mammalian cells, and RNA optimization (so as to provide a stable RNA or mRNA for delivery to a subject or a cell of the subject). In an embodiment, an isolated nucleic acid molecule, such as a polynucleotide, comprising a nucleotide sequence encoding a polypeptide or peptide antigen, such as an influenza virus HA polypeptide antigen, is provided. In certain embodiments, the nucleotide sequence encoding the HA polypeptide is at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a polynucleotide encoding an HA polypeptide of the present disclosure. In an embodiment, an isolated nucleic acid molecule (polynucleotide) comprising a nucleotide sequence encoding the HA and / or an NA antigen proteins contained in the pentavalent / octavalent composition / vaccine described herein is provided. In certain embodiments, the nucleotide sequence encoding the HA and / or the NA polypeptide is at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a polynucleotide encoding an HA or NA antigen protein (polypeptide) sequence of the present disclosure. In an embodiment, the encoding polynucleotide sequence lacks the start codon encoding an N-terminal methionine. In an embodiment, an isolated nucleic acid molecule, such as a polynucleotide, comprising a nucleotide sequence encoding a polypeptide or peptide antigen, such as an influenza virus NA polypeptide, is provided. In certain embodiments, the nucleotide sequence encoding the NA polypeptide is at least 94%, at least 95%, at least 96%, at least 97%, at least Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 98%, or at least 99% identical to a polynucleotide encoding an HA polypeptide of the present disclosure. In other embodiments, the nucleotide sequence encoding an influenza virus NA polypeptide that is at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a polynucleotide encoding an influenza virus NA polypeptide sequence of the present disclosure lacks the start codon encoding an N-terminal methionine. Vectors containing one or more nucleotide sequences encoding the five or eight HA and NA antigen proteins contained in the pentavalent / octavalent composition / vaccine as described herein are provided. In some embodiments, the vectors comprise a nucleotide sequence encoding the HA and NA antigen proteins (polypeptides) as set forth in SEQ ID NOs: 11-18, for example. In some embodiments, the nucleotide sequence may be at least 90%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to a polynucleotide encoding an HA or NA antigen of the present disclosure. In some embodiments, the vector further includes nucleic acid sequences, e.g., a promoter, enhancer, or other regulatory sequence, operably linked to the nucleotide sequence encoding the HA and NA antigens of the pentavalent / octavalent composition / vaccine. In some embodiments, the nucleotide sequence of the vector is at least 85%, at least 90%, at least 95%, at least 98% or at least 99% identical to a polynucleotide encoding an HA or NA polypeptide of the disclosure (see, e.g., Table 4). In particular embodiments, the nucleotide sequence of the vector comprises the polynucleotide encoding an HA or NA polypeptide of the disclosure. In a particular embodiment, the promoter is a cytomegalovirus (CMV) promoter. In embodiments, the vector is a prokaryotic or eukaryotic vector. In an embodiment, the vector is an expression vector, such as a eukaryotic (e.g., mammalian) expression vector. In another embodiment, the vector is a plasmid (prokaryotic or bacterial) vector. In another embodiment, the vector is a viral vector. In an embodiment, the vector comprises DNA, RNA, or mRNA. In an embodiment, the encoding nucleic acid sequences are contained in a lipid nanoparticle (LNP). The vectors used to express the influenza virus HA and NA antigens in the pentavalent / octavalent composition / vaccine as described herein may be any suitable expression vectors known and used in the art. The vectors can be, for example, mammalian expression vectors, viral vectors, or nucleic acids, e.g., mRNA or DNA. In some embodiments, the vector is the pTR600 expression vector (U.S. Patent Application Publication No.2002 / 0106798, herein incorporated by reference; Ross et al., 2000, Nat Immunol.1(2):102-103; and Green et al., 2001, Vaccine 20:242-248), or a vector as described in the Examples herein. A host cell is transfected Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 or transduced with an expression vector as known and used in the art under conditions sufficient to allow for expression of the HA and NA antigen proteins in the pentavalent / octavalent composition / vaccine in the cell. Isolated cells containing the vectors are also provided. In an embodiment, the HA and NA antigens are recombinant and / or recombinantly produced. In some embodiments, the recombinant, broadly reactive HA and NA influenza virus antigen proteins contained in the pentavalent / octavalent composition / vaccine as described herein may be fused to a heterologous amino acid sequence to form a fusion protein. In addition, the HA and NA antigen sequences may contain tag sequences or other sequences for expression and / or isolation from a cell. Also provided are non-naturally occurring, broadly reactive influenza virus antigen polypeptides as described herein, such as broadly reactive H1, H2, H3, H5, H7, or IBV influenza HA polypeptides. In certain embodiments, the amino acid sequence of the polypeptide is at least 95% to 99% (inclusive) identical to the amino acid sequence of an HA polypeptide of the disclosure. In particular embodiments, the amino acid sequence of the influenza HA polypeptide that is at least 95% to 99% (inclusive) identical to the amino acid sequence of an HA polypeptide of the disclosure lacks the N-terminal methionine residue. In a particular embodiment, the amino acid sequence of the influenza HA polypeptide is at least 95% to 99% (inclusive) identical to the amino acid sequence of an HA polypeptide of the disclosure. Also provided are non-naturally occurring, broadly reactive influenza virus NA antigen polypeptides as described herein, such as broadly reactive H1, H2, H3, H5, H7, or IBV influenza NA polypeptides. In certain embodiments, the amino acid sequence of the polypeptide is at least 95% to 99% (inclusive) identical to the amino acid sequence of an NA (e.g., N1 or N2) polypeptide of the disclosure. In particular embodiments, the amino acid sequence of the influenza NA (e.g., N1 or N2) polypeptide that is at least 95% to 99% (inclusive) identical to the amino acid sequence of an NA of the disclosure lacks the N-terminal methionine residue. In a particular embodiment, the amino acid sequence of the influenza NA polypeptide is at least 95% to 99% (inclusive) identical to the amino acid sequence of the NA polypeptides of the present disclosure. In some embodiments, fusion proteins comprising the broadly reactive influenza virus antigen polypeptides described herein, e.g., without limitation, the HA or NA polypeptides disclosed herein, are also provided. In some embodiments, the influenza HA or NA polypeptide can be fused to any heterologous amino acid sequence to form the fusion protein. For example, an HA or NA polypeptide sequence may be fused at the C- and / or N-terminus to one or more of Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 a signal sequence (e.g., a CD5 signal sequence), a His tag (e.g., a 6x His-tag), a linker peptide, a cleavage site (e.g., a thrombin cleavage site), and a tetrabrachion domain. Also provided are virus-like particles (VLPs), in particular, H1, H2, H3, H5, H7, and IBV influenza virus VLPs, containing the immunogenic, broadly reactive protein antigens HA and NA of the pentavalent / octavalent composition / vaccine, as described herein, or polynucleotides encoding the antigens. In certain embodiments, the HA protein of the VLP is at least or equal to 94%, at least or equal to 95%, at least or equal to 96%, at least or equal to 97%, at least or equal to 98%, at least or equal to 99% or 100% identical to the influenza virus HA proteins of the disclosure. The virus or influenza VLPs can further include any additional or auxiliary viral or influenza proteins necessary to form the virus particle. In certain embodiments, the virus or influenza VLPs further include influenza neuraminidase (NA) protein (e.g., N1 or N2), influenza matrix (M1) protein, or both. In certain embodiments, the NA protein (e.g., N1 or N2) of the VLP is at least or equal to 94%, at least or equal to 95%, at least or equal to 96%, at least or equal to 97%, at least or equal to 98%, at least or equal to 99% or 100% identical to the NA proteins of the present disclosure. In an embodiment, an influenza VLP containing H1, H2, H3, H5, and H7 and IBV influenza virus HA and NA polypeptide antigen components of the pentavalent / octavalent composition / vaccine as described herein is produced by transfecting a host cell with a vector (or multiple vectors) containing one or more polynucleotides encoding the HA, HA1, HA2, and / or NA polypeptide antigens of the pentavalent / octavalent composition / vaccine. Also provided in a certain embodiment is an influenza VLP containing an influenza HA polypeptide, or HA1 or HA2 polypeptide, as described herein, produced by transfecting a host cell with a vector encoding the influenza virus HA, HA1, or HA2 polypeptide, a vector encoding an influenza NA protein and a vector encoding an influenza M1 protein, under conditions sufficient to allow for expression of the influenza virus HA, NA, and M1 proteins. In an embodiment, a nucleic acid, e.g., DNA or mRNA, encoding the HA and NA polypeptide antigens of the pentavalent / octavalent composition / vaccine are used for transfecting a host cell. In an embodiment, the host cell may be transfected with a vector encoding an influenza M1 protein, under conditions sufficient to allow for expression of the influenza virus HA, NA and M1 proteins in the cell. Such VLPs comprising the pentavalent / octavalent composition / vaccine HA and NA sequences as described herein and used as immunogens generate antibodies having high hemagglutinin inhibition (HAI) titers and neuraminidase inhibition (NAI) titers against different strains of influenza virus types as described. Collections of plasmids (vectors or nucleic acid / polynucleotides) are also contemplated. In certain embodiments, the collection of plasmids includes a plasmid encoding an influenza Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 virus NA, a plasmid encoding an influenza MA, and a plasmid encoding a broadly reactive influenza virus HA protein as described herein. In certain embodiments, the collection of plasmids includes one or more plasmids containing nucleic acids encoding the components of the pentavalent / octavalent composition / vaccine, namely, the broadly reactive influenza virus HA and NA antigens as described herein. In embodiments, the HA and NA antigens are full length or soluble polypeptides and comprise the amino acid sequences as described herein. In embodiments, the polynucleotide sequences described herein encode the full length or soluble HA and / or NA polypeptides. In some embodiments, the nucleotide sequences encodes codon- optimized influenza HA and NA proteins. In some embodiments, the nucleotide sequence encoding an influenza HA protein of the HA-encoding plasmid is at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to a polynucleotide encoding an HA amino acid sequence of the present disclosure. In some embodiments, the nucleotide sequence encoding a codon-optimized influenza HA protein of the HA-encoding plasmid is at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to a polynucleotide encoding an influenza HA amino acid sequence of the present disclosure. In some embodiments, the nucleotide sequence encoding an influenza NA protein of the NA- encoding plasmid is at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to a polynucleotide encoding an NA amino acid sequence of the present disclosure. In some embodiments, the nucleotide sequence encoding a codon-optimized influenza NA protein of the NA-encoding plasmid is at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to a polynucleotide encoding an influenza NA amino acid sequence of the present disclosure. In the context of the present disclosure, “broadly reactive” or “broadly active” means that the influenza virus protein (e.g., an H1, H2, H3, H5, H7, or IBV HA protein sequence and an N1 or N2 NA protein sequence) contained in the pentavalent / octavalent immunogen / vaccine is immunogenic and contains a diversity of epitopes (antigenic determinants) that elicit in a subject an immune response (e.g., neutralizing antibodies directed against the epitopes contained in the broadly reactive protein immunogen, frequently accompanied by a T-cell response) sufficient to treat disease or pathology, and / or the symptoms thereof associated with influenza virus infection, and / or to inhibit, neutralize, or prevent infection, caused by most or all of the influenza viruses within a specific subtype, or by related virus strains. In embodiments, the broadly reactive HA H1, H2, H3, H5, H7, and IBV, and NA N1 and NA N2 influenza virus-derived antigen proteins of the pentavalent / octavalent composition / vaccine used as an immunogen can elicit a protective immune response against numerous H1, H2, H3, H5, and H7 influenza virus isolates, as well as Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 IBV isolates, such as about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 96%-99% of the known H1, H2, H3, H5, H7, and / or IBV influenza virus isolates. Compositions and Pharmaceutical Compositions for Administration A pentavalent / octavalent composition or formulation comprising the five or eight, isolated, broadly reactive influenza HA and NA protein antigens, or a fusion protein or VLP comprising such a pentavalent / octavalent composition as described herein, is provided. In some embodiments, the composition further comprises a pharmaceutically or physiologically acceptable carrier, excipient, or vehicle. In some embodiments, at least one adjuvant (a pharmacological or immunological agent that modifies or boosts an immune response, e.g. to produce more antibodies that are longer-lasting) is also employed. For example, without limitation, the adjuvant can be an inorganic compound, such as alum, aluminum hydroxide, or aluminum phosphate; mineral or paraffin oil; squalene; detergents such as Quil A; plant saponins; Freund's complete or incomplete adjuvant, a biological adjuvant (e.g., cytokines such as IL-1, IL-2, or IL-12); and / or bacterial products such as killed Bordetella pertussis, or toxoids; or immuno-stimulatory oligonucleotides (such as CpG oligonucleotides). In an embodiment, a cyclic dinucleotide adjuvant, such as c-di-AMP, is added to or included in a formulation of the pentavalent / octavalent composition / vaccine or preparation for administration, immunization, or delivery to a subject to ensure the quality of the immune response required for the clearance of the influenza virus by the induction of a strong, fast, and high avidity antibody response and the elicitation of an appropriate cellular immune response, thereby promoting enhanced binding, neutralization, and / or killing activity of the elicited antibodies and / or the immune cells generated by the immune response. Administration of the pentavalent / octavalent composition / vaccine as described, as well as VLPs or other delivery vehicles and forms, can be accomplished by single or multiple doses. The dose administered to a subject should be sufficient to induce a beneficial therapeutic response in a subject over time, such as to inhibit, neutralize, block, reduce, diminish, ameliorate, protect against, abate, abrogate, or prevent disease associated with infection by influenza virus (e.g., H1, H2, H3, H5, H7, IBV, N1 and N2 influenza viruses). The dose required will vary from subject to subject depending on the species, age, weight and general condition of the subject, by the severity of the infection being treated, by the particular composition being used and by the mode of administration. An appropriate dose can be determined by a person skilled in the art, such as a clinician or medical practitioner, using only routine medical knowledge and / or medical experimentation. Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 In an embodiment, the pentavalent / octavalent composition / vaccine or a formulation thereof comprising the isolated, immunogenic HA and NA antigens as described, in combination with c-di-AMP and with other potential immune stimulators, improves the effect of c-di-AMP, allowing dose splitting or the addition of complementary properties to the resulting formulation, in particular, in terms of effector functions responsible for virus clearance. Provided also is a method of treating or preventing influenza virus infection, disease onset or progression, and / or disease severity, in some cases by the nasal or mucosal route, by administering the pentavalent / octavalent composition / vaccine or a formulation thereof in a dose range that elicits an effective antibody and / or cellular immune response. In a specific embodiment, the pentavalent / octavalent composition / vaccine, or a formulation thereof, contains the five or eight, isolated HA and NA COBRA protein antigens (e.g., Y4, NG3, N1I, N2A, BC3 or BC2, Z1, IAN8, and Q6 listed in Table 4) in a range of concentrations, which allows a stronger and well- modulated immune response. In some embodiments, the compositions of the disclosure contain about equal masses of each of the antigens. In an embodiment, the compositions of the disclosure contain from about 0.01 mg / mL to about 10 mg / mL of total antigens. In embodiments, the compositions of the disclosure contain about or at least about 0.001 mg / mL, 0.01 mg / mL, 0.1 mg / mL, 1 mg / mL, 5 mg / mL, or 10 mg / mL total antigens. In embodiments, the compositions of the disclosure contain no more than about 0.01 mg / mL, 0.1 mg / mL, 1 mg / mL, 5 mg / mL, or 10 mg / mL total antigens. In an embodiment, the compositions of the disclosure contain from about 0.020 mg / mL to 0.300 mg / mL or from about 0.01-10 mg / mL of c-di-AMP in a physiologically acceptable diluent or buffer, for example, phosphate buffered saline solution (PBS). In some embodiments, the compositions of the disclosure contain about or at least about 0.01 mg / mL, 0.1 mg / mL, 1 mg / mL, 5 mg / mL, or 10 mg / mL adjuvant (e.g., c-di-AMP). In some embodiments, the compositions of the disclosure contain no more than about 0.1 mg / mL, 1 mg / mL, 5 mg / mL, or 10 mg / mL adjuvant (e.g., c-di-AMP). In an embodiment, the concentration range comprises from 0.010 mg / mL to 0.500 mg / mL or from 0.020 mg / mL to 0.300 mg / mL of c-di-AMP in a physiologically acceptable diluent or buffer, for example, phosphate buffered saline solution (PBS). In a specific embodiment, 50 μg of c-di-AMP is employed as adjuvant and used in conjunction with the pentavalent / octavalent composition / vaccine as described herein. In an embodiment, the pentavalent / octavalent composition / vaccine, or a formulation thereof and adjuvant are administered in a liquid formulation in a volume of 0.01 mL to 5.0 mL, or in a volume of 0.05 mL to 0.5 mL, or in a volume of 0.05 mL to 1.0 mL, or in a volume of 0.05 mL or 1.0 mL. Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 The pentavalent / octavalent composition / vaccine, or a formulation thereof, as described, and VLPs comprising the pentavalent / octavalent composition / vaccine can be administered to a subject by any of the routes normally used for introducing a recombinant protein, composition containing the recombinant protein, polynucleotide encoding the protein, or recombinant virus into a subject. Routes and methods of administration include, without limitation, intradermal, intramuscular, intraperitoneal, intrathecal, parenteral, such as intravenous (IV) or subcutaneous (SC), vaginal, rectal, intranasal, inhalation, intraocular, intracranial, or oral. Parenteral administration, such as subcutaneous, intravenous or intramuscular administration, is generally achieved by injection (immunization). Injectables can be prepared in conventional forms and formulations, either as liquid solutions or suspensions, solid forms (e.g., lyophilized forms) suitable for solution or suspension in liquid prior to injection, or as emulsions. Injection solutions and suspensions can be prepared from sterile powders, granules, and tablets. Administration can be systemic or local. In an embodiment, the pentavalent / octavalent composition / vaccine, or a formulation thereof, is administered by mucosal route (e.g., intranasal, sublingual, intra-pulmonic, oral) or, alternatively, by parenteral route (e intramuscular, subcutaneous, intradermal), alone or in conjunction with alum or other depot adjuvants and / or with c-di-AMP as an adjuvant. The pentavalent / octavalent composition / vaccine, or a formulation thereof, may include or be formulated with one or more different adjuvants (e.g., c-di-AMP) as a component of the composition / vaccine formulation, or may be mixed with one or more adjuvants (or other physiologically acceptable components) at the time of product administration. In a specific embodiment, the pentavalent / octavalent composition / vaccine, or a formulation thereof, is administered in schedules of immunization or accelerated schedules of administration comprising administration every week, every 15 days, every month, every 6 months, every year, or administration that is adjusted to requirement or need, as well as in long- term schedules of administration tailored so as to time the boosting with the contraction phase of the germinal center formation to foster hypersomatic mutation and affinity maturation in antibodies generated by the immune system in response to immunization with the pentavalent / octavalent composition / vaccine. In embodiments, the pentavalent / octavalent composition / vaccine, or a formulation or preparation thereof (e.g., physiologically or pharmaceutically acceptable compositions as described herein) includes, without limitation, sterile aqueous or non-aqueous solutions, suspensions, and emulsions. Nonlimiting examples of non-aqueous solvents include propylene glycol, polyethylene glycol, vegetable oils, such as olive oil and canola oil, and injectable Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 organic esters, such as ethyl oleate. Aqueous carriers include water, alcoholic / aqueous solutions, emulsions or suspensions, including saline and buffered media. Parenteral vehicles include, for example, sodium chloride (saline) solution, Ringer's dextrose, dextrose and sodium chloride, lactated Ringer's, or fixed oils. Intravenous vehicles include, for example, fluid and nutrient replenishers, electrolyte replenishers (such as those based on Ringer's dextrose), and the like. Preservatives and other additives may also be present in such compositions and preparations, such as, for example, antimicrobials, antioxidants, chelating agents, colorants, stabilizers, inert gases and the like. Some of the compositions may potentially be administered as a pharmaceutically acceptable acid- or base-addition salt, formed by reaction with inorganic acids, such as hydrochloric acid, hydrobromic acid, perchloric acid, nitric acid, thiocyanic acid, sulfuric acid, and phosphoric acid, and organic acids, such as formic acid, acetic acid, propionic acid, glycolic acid, lactic acid, pyruvic acid, oxalic acid, malonic acid, succinic acid, maleic acid, and fumaric acid, or by reaction with an inorganic base such as sodium hydroxide, ammonium hydroxide, potassium hydroxide, and organic bases such as mono-, di-, tri-alkyl and aryl amines and substituted ethanolamines. Provided herein are pharmaceutical compositions which include a therapeutically effective amount of the described pentavalent / octavalent composition / vaccine containing five or eight, isolated, non-naturally occurring, broadly reactive influenza virus HA and NA protein antigens, or influenza VLPs, alone, or in combination with a pharmaceutically acceptable carrier, excipient, or diluent. In embodiments, the influenza virus HA and NA antigens contained in the pentavalent / octavalent composition / vaccine include those of the H1, H2, H3, H5, H7, and IBV influenza viruses having the sequences as set forth and described herein. Pharmaceutically acceptable carriers include, but are not limited to, saline, buffered saline, dextrose, water, glycerol, ethanol, and combinations thereof. The carrier and composition can be sterile, and the formulation suits the mode of administration. The composition can also contain minor amounts of wetting or emulsifying agents, or pH buffering agents. The composition can be a liquid or aqueous solution, suspension, emulsion, dispersion, tablet, pill, capsule, powder, or sustained release formulation. A liquid or aqueous composition can be lyophilized and reconstituted with a solution or buffer prior to use. The composition can be formulated as a suppository, with traditional binders and carriers such as triglycerides. Oral formulations can include standard carriers, such as pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, and magnesium carbonate. Any of the commonly known pharmaceutical carriers, such as sterile saline solution or sesame oil, can be used. The medium can also contain Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 conventional pharmaceutical adjunct materials such as, for example, pharmaceutically acceptable salts to adjust the osmotic pressure, buffers, preservatives and the like. Methods of Treatment, Administration and Delivery Methods of treating a disease or infection, or symptoms thereof, caused by or associated with influenza virus (e.g., H1, H2, H3, H5, H7, or IBV influenza viruses) are provided. The methods comprise administering a therapeutically effective amount of the pentavalent / octavalent composition / vaccine, or a formulation thereof, containing five or eight, isolated, broadly reactive HA and NA influenza virus antigens, which are immunogenic, as described herein, or polynucleotides encoding the HA and NA antigens, or a pharmaceutical composition comprising the immunogens, or a vaccine (e.g., a VLP vaccine) as described herein to a subject (e.g., a mammal), in particular, a human subject, a non-human animal or veterinary subject (e.g., an avian subject). One embodiment involves a method of treating a subject suffering from, at risk of, or susceptible to, disease or infection, or a symptom thereof, caused by influenza virus. The method includes administering to the subject (e.g., a mammalian subject), an amount or a therapeutic amount of the immunogenic pentavalent / octavalent composition / vaccine, or a formulation thereof, as described herein containing five or eight, isolated, broadly reactive HA and NA influenza virus antigens, or polynucleotides encoding the antigens, or HA and / or NA VLPs, sufficient to treat the disease, infection, or symptoms thereof, caused by one or more influenza virus strains under conditions in which the disease, infection, and / or the symptoms thereof are treated. As described above, the octavalent composition / vaccine, or a formulation thereof, is composed of eight, broadly reactive influenza virus HA and NA immunogenic protein and nucleic acid sequences which comprise a set of the following: Y4, NG3, N1I, N2A, BC3 or BC2, Z1, IAN8, and Q6. In various embodiments, the antigen is full-length (FL) antigen, soluble-form (“s”) antigen, a fusion protein comprising the same, or fragments thereof, as provided herein. As described above, the pentavalent composition / vaccine, or a formulation thereof, is composed of five, broadly reactive influenza virus HA and NA immunogenic protein and nucleic acid sequences which comprise the following: amino acid SEQ ID NO: 1 of “Y2”, a full length HA antigen protein of an H1 influenza virus strain (“Y2 (H1 HA)” herein), amino acid SEQ ID NO: 2 of “NG2”, a full length HA antigen protein of an H3 influenza virus strain (“NG2 (H3 HA)” herein), amino acid SEQ ID NO: 3 of “BC2”, a full length HA antigen protein of influenza B virus (IBV) (“BC2 (IBV HA)” herein), amino acid SEQ ID NO: 4 of “N1-I”, a full length neuraminidase (NA) N1 antigen protein (“N1-I (N1 NA)” herein), and amino acid SEQ ID NO: Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 5 of “N2-B”, a full length N2 NA antigen protein (“N2-B (N2 NA)” herein). In an embodiment, soluble amino acid protein sequences of these HA and NA antigens are also provided, namely, SEQ ID NO: 6 (soluble Y2 amino acid sequence (“sY2”)), SEQ ID NO: 7 (soluble NG2 amino acid sequence (“sNG2”)), SEQ ID NO: 8 (soluble BC2 amino acid sequence (“sBC2”)), SEQ ID NO: 9 (soluble N1-I amino acid sequence (“sN1-I”))...

Claims

Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 What is claimed is:

1. A pentavalent or octavalent immunogen or vaccine, wherein the pentavalent immunogen or vaccine comprises five, isolated, non-naturally occurring and immunogenic influenza virus hemagglutinin (HA) and neuraminidase (NA) antigens, or antigen binding portions thereof, or polynucleotides encoding the antigens or antigen-binding portions thereof, wherein the antigens comprise the following amino acid sequences: SEQ ID NO: 1 (Y2 (H1 HA)), SEQ ID NO: 2 (NG2 (H3 HA)), SEQ ID NO: 3 (BC2 (IBV HA)), SEQ ID NO: 4 (N1-I (N1 NA)), and SEQ ID NO: 5 (N2-B (N2 NA)); and wherein the octavalent immunogen or vaccine comprises eight, isolated, non-naturally occurring and immunogenic influenza virus hemagglutinin (HA) and neuraminidase (NA) antigens, or antigen-binding portions thereof, or polynucleotides encoding the antigens or antigen-binding portions thereof, wherein the antigens comprise the following amino acid sequences: a) SEQ ID NO: 51 (Y4 (H1 HA)), b) SEQ ID NO: 40 (NG3 (H3 HA)), c) SEQ ID NO: 4 (N1I (N1 NA)), d) SEQ ID NO: 65 (N2A (N2 NA)), e) SEQ ID NO: 69 (BC3 (IBV HA)) or SEQ ID NO: 3 (BC2 (IBV HA)), f) SEQ ID NO: 56 (Z1 (H2 HA)), g) SEQ ID NO: 34 (IAN8 (H5 HA)), and h) SEQ ID NO: 45 (Q6 (H7 HA)).

2. A pentavalent or octavalent immunogen or vaccine, wherein the pentavalent immunogen or vaccine comprises five, isolated, non-naturally occurring and immunogenic influenza virus hemagglutinin (HA) and neuraminidase (NA) antigens, which are soluble antigens, or antigen-binding portions thereof, or polynucleotides encoding the antigens or antigen-binding portions thereof, wherein the antigens comprise the following amino acid sequences: a) SEQ ID NO: 6 (sY2 (H1 HA)), b) SEQ ID NO: 7 (sNG2 (H3 HA)), c) SEQ ID NO: 8 (sBC2 (IBV HA)), d) SEQ ID NO: 9 (sN1-I (N1 NA)), and e) SEQ ID NO: 10 (sN2-B (N2 NA)); and wherein the octavalent immunogen or vaccine comprises eight, isolated, non-naturally occurring and immunogenic influenza virus hemagglutinin (HA) and neuraminidase (NA) antigens, which are soluble antigens, or antigen-binding portions thereof, or polynucleotides encoding the antigens or antigen-binding portions thereof, wherein the antigens comprise the following amino acid sequences: a) SEQ ID NO: 53 (sY4 (sH1 HA)), b) SEQ ID NO: 42 (sNG3 (sH3 HA)), c) SEQ ID NO: 62 (sN1I (sN1 NA)), d) SEQ ID NO: 67 (sN2A (sN2 NA)), e) SEQ ID NO: 71 (sBC3 (sIBV HA)) or SEQ ID NO: 8 (sBC2 (sIBV HA)), f) SEQ ID NO: 58 (sZ1 (sH2 HA)), g) SEQ ID NO: 36 (sIAN8 (sH5 HA)), and h) SEQ ID NO: 47 (sQ6 (sH7 HA)).Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 3. The pentavalent or octavalent immunogen or vaccine of claim 2, wherein the polynucleotides encoding the pentavalent immunogen or vaccine comprise SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, and SEQ ID NO: 15, respectively, and wherein polynucleotides encoding the octavalent immunogen or vaccine comprise SEQ ID NOs: 68, 37, 43, 48, 54, 59, 63, 72, and / or 13, optionally, wherein the polynucleotides comprise DNA, RNA, or mRNA.

4. The pentavalent or octavalent immunogen or vaccine of claim 1, wherein the polynucleotides encoding the HA or NA antigens of the pentavalent immunogen or vaccine comprise SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, and SEQ ID NO: 20; and wherein the polynucleotides encoding the HA or NA antigens of the octavalent immunogen or vaccine comprise SEQ ID NO: 66, SEQ ID NO: 35, SEQ ID NO: 41, SEQ ID NO: 46, SEQ ID NO: 52, SEQ ID NO: 57, SEQ ID NO: 19, SEQ ID NO: 70, and / or SEQ ID NO: 18, optionally, wherein the polynucleotides comprise DNA, RNA, or mRNA.

5. The pentavalent or octavalent immunogen or vaccine of claim 2, wherein (i) one or more of the antigens further comprises between 5 and 10 consecutive His amino acids, and / or wherein (ii) one or more of the HA antigens comprises the between 5 and 10 consecutive His amino acids at the C-terminus; or wherein (iii) one or more of the soluble antigens further comprises a peptide having an amino acid sequence comprising MPMGSLQPLATLYLLGMLVASVLSAHHHHHHGSGSLVPRGSPSRSIINETADDIVYRLTVIIDD RYESLKNLITLRADRLEMIINDNVSTILASIGSGTG (SEQ ID NO: 33) fused to the N-terminus of the antigen; or wherein (iv) one or more of the HA antigens further comprises a peptide comprising one of the following amino acid sequences fused to the C-terminus of the antigen: GTGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGLNDIFEAQKIEWHEGHHHHHH (SEQ ID NO: 23); GSGYIPEAPRDGQAYVRKDGEWVLLSTFLGLNDIFEAQKIEWHEGHHHHHHGS (SEQ ID NO:Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 IGSGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGLNDIFEAQKIEWHEGHHHHHH (SEQ ID NO: 5);or GYIPEAPRDGQAYVRKDGEWVLLSTFLGSGLNDIFEAQKIEWHEGHHHHHH (SEQ ID NO: 17).

6. A composition or formulation comprising the pentavalent or octavalent immunogen or vaccine of any one of claims 1-5, optionally comprising a pharmaceutically acceptable excipient, diluent, or carrier.

7. A virus-like particle (VLP) comprising the pentavalent or octavalent immunogen or vaccine of any one of claims 1-3, or a composition comprising the VLP, and optionally comprising a pharmaceutically acceptable carrier, diluent, or excipient.

8. The composition or formulation of claim 6 or the virus-like particle (VLP) or composition thereof of claim 7, further comprising an adjuvant.

9. A method of generating or eliciting an immune response in a subject, or of treating, ameliorating, or abrogating disease and / or symptoms thereof associated with influenza virus infection in a subject, the method comprising administering to the subject an effective amount of the pentavalent or octavalent immunogen or vaccine of any one of claims 1-5, the composition or formulation of claim 6 or 8, or the virus-like particle (VLP) or composition thereof of claim 7.

10. The method of claim 9, wherein the influenza virus comprises influenza subtype A virus and / or influenza subtype B virus; wherein the immune response is generated or elicited against hemagglutinin (HA) and neuraminidase (NA) antigens of influenza virus subtypes; and / or wherein the immune response is generated or elicited against hemagglutinin (HA) and neuraminidase (NA) antigens of influenza virus subtypes, which comprise H1, H2, H3, H5, H7, and IBV.

11. The composition or formulation of claim 6, the virus-like particle (VLP) or composition thereof of claim 7, or the method of claim 9 or 10, wherein the pentavalent or octavalent immunogen or vaccine, the composition or formulation, the virus-like particle (VLP), or the pharmaceutical composition or formulation is formulated for nasal administration and / or is delivered intranasally, and / orAttorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 wherein an adjuvant is admixed with the pentavalent or octavalent immunogen or vaccine, the composition or formulation, the virus-like particle (VLP), or the pharmaceutical composition or formulation, or wherein the adjuvant is concomitantly administered to the subject.

12. The composition or formulation, the virus-like particle (VLP) or composition thereof, or the method of claim 11, wherein the adjuvant is a cyclic dinucleotide; or wherein the adjuvant is c-di-AMP; or wherein the adjuvant comprises a c-di-AMP (CDN) adjuvant according to the formula:, wherein A, A’ is independently from one another S or O; X is independently from one another S, N, O, CH2; Y, Y’ is independently from one another NH, CH2, O; Z, Z’ is independently from one another NH, CH2, O; R1is independently from one another hydrogen or O or absent; R2 is independently from one another NH2, O, H, or a hydrogen; R3 is independently from one another absent if a covalent bond is present between the Z or Z’ and the C atom, or is hydrogen, OH, halogen, a straight or branched C1-C6alkyl group, or a straight or branched C1-C6 alkoxy group which may optionally be substituted; R4 is independently from one another hydrogen, halogen, or a straight or branched C1-C6 alkyl group, which may optionally be substituted; and “ ...” is a single or double bond; or conjugates thereof, and salts or solvates thereof; optionally, wherein the CDN has a purine residue selected from adenine, xanthine or hypoxanthine, or combinations thereof; or wherein both purine residues in the CDN comprise adenine; orAttorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 wherein the CDN is characterized in that R3 is a OH group, X is an oxygen atom and Y, Y’, Z and Z’ are oxygen; and / or wherein the CDN is a compound selected from the group of cyclic bis (3’-5’) diadenylic acid (CDA) or c-di-AMP, c-di-IMP, c-IAMP, or a cyclic di-AMP thiophosphate, c-di-MP thiophosphate and c-IAMP thiophosphate.

13. A pentavalent or octavalent immunogen or vaccine, wherein the pentavalent immunogen or vaccine comprises five, isolated, non-naturally occurring and immunogenic influenza virus hemagglutinin (HA) and neuraminidase (NA) antigens or antigen-binding portions thereof, or polynucleotides encoding the antigens or antigen-binding portions thereof, wherein the antigens comprise the following amino acid sequences: (i) SEQ ID NO: 1 (Y2 (H1 HA)), SEQ ID NO: 2 (NG2 (H3 HA)), SEQ ID NO: 3 (BC2 (IBV HA)), SEQ ID NO: 4 (N1-I (N1 NA)), and SEQ ID NO: 5 (N2-B (N2 NA)); or (ii) SEQ ID NO: 6 (sY2 (H1 HA)), SEQ ID NO: 7 (sNG2 (H3 HA)), SEQ ID NO: 8 (sBC2 (IBV HA)), SEQ ID NO: 9 (sN1-I (N1 NA)), and SEQ ID NO: 10 (sN2-B (N2 NA)); or wherein the octavalent immunogen or vaccine comprises eight, isolated, non-naturally occurring and immunogenic influenza virus hemagglutinin (HA) and neuraminidase (NA) antigens or antigen-binding portions thereof, or polynucleotides encoding the antigens or antigen-binding portions thereof, wherein the antigens comprise the following amino acid sequences: i) a) SEQ ID NO: 51 (Y4 (H1 HA)), b) SEQ ID NO: 40 (NG3 (H3 HA)), c) SEQ ID NO: 4 (N1I (N1 NA)), d) SEQ ID NO: 65 (N2A (N2 NA)), e) SEQ ID NO: 69 (BC3 (IBV HA)) or SEQ ID NO: 3 (BC2 (IBV HA)), f) SEQ ID NO: 56 (Z1 (H2 HA)), g) SEQ ID NO: 34 (IAN8 (H5 HA)), and h) SEQ ID NO: 45 (Q6 (H7 HA)); or ii) a) SEQ ID NO: 53 (sY4 (sH1 HA)), b) SEQ ID NO: 42 (sNG3 (sH3 HA)), c) SEQ ID NO: 62 (sN1I (sN1 NA)), d) SEQ ID NO: 67 (sN2A (sN2 NA)), e) SEQ ID NO: 71 (sBC3 (sIBV HA)) or SEQ ID NO: 8 (sBC2 (sIBV HA)), f) SEQ ID NO: 58 (sZ1 (sH2 HA)),Attorney Docket No.173093-011902 / PCT Client Reference: 2024-063-03 Date of Deposit: February 21, 2025 g) SEQ ID NO: 36 (sIAN8 (sH5 HA)), and h) SEQ ID NO: 47 (sQ6 (sH7 HA)); wherein the pentavalent or octavalent immunogen or vaccine is formulated or administered with a c-di-AMP cyclic dinucleotide adjuvant for intranasal administration; optionally, wherein the HA and NA antigens are recombinant and / or are recombinantly produced.

14. A method of treating, ameliorating, or abrogating disease and / or symptoms thereof associated with influenza virus infection in a subject, the method comprising intranasally administering to the subject an effective amount of the pentavalent or octavalent immunogen or vaccine of claim 13 and the c-di-AMP adjuvant.

15. The method of claim 14, wherein the method generates a prophylactic or therapeutic immune response in the subject; wherein the subject is a human subject, a non-human subject, or a veterinary subject; and / or wherein the method (i) treats or prevents the onset or progression of disease associated with or caused by influenza virus infection; (ii) reduces horizontal transfer of influenza virus from an infected subject to a susceptible host; (iii) generates a rapid immune response following a weekly, biweekly or monthly administration schedule; and / or (iv) comprises administration using a prime-boost or prime-pull regimen of immunization or vaccination.

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