Multivalent subtype influenza vaccine

Abstract

The present disclosure relates to multivalent subtype influenza vaccines to treat and prevent influenza-associated diseases, disorders or conditions.

Description

[0001] Multivalent subtype influenza vaccine Related application data The present application claims priority from Australian Patent Application No.2023901936 filed on 19 June 2023 entitled “Multivalent subtype influenza vaccine”. The entire contents of which is hereby incorporated by reference. Sequence listing The present application is filed together with a Sequence Listing in electronic form. The entire contents of the Sequence Listing are hereby incorporated by reference. Technical field The present disclosure generally relates to multivalent subtype influenza vaccines to treat and prevent influenza-associated diseases, disorders or conditions. Background Influenza is a major respiratory disease in mammalian species and is responsible for substantial mortality, morbidity and economic losses each year. Three broad types of influenza viruses are recognised, Type A, Type B and Type C, which are defined by the absence of serological cross- reactivity between their internal proteins. Influenza A viruses are further classified into subtypes based on antigenic and genetic differences of their glycoproteins, the haemagglutinin (HA) and neuraminidase (NA) proteins. Current approved seasonal quadrivalent influenza vaccines (QIV) contain at least one viral protein from each of four circulating influenza viruses in humans; typically, A(H1N1), A(H3N2), B / Yamagata-like and B / Victoria-like viruses. However, no B / Yamagata-like viruses have been detected since March 2020, despite isolation of A(H1N1), A(H3N2) and B / Victoria-like viruses. Thus, inclusion of a representative virus from the B / Yamagata-like lineage may be reconsidered in future QIV recommendations. New bivalent (BIV), trivalent (TIV) or QIVs may be developed as a result. Summary The present disclosure is based on the surprising finding that vaccination with two influenza HAs from antigenically distinct influenza A virus H3 subtype strains is capable of inducing a protective antibody response against other, non-vaccine influenza A virus H3 subtype strains, including those that emerge after the vaccine strains. This immunogenic advantage has been demonstrated to occur even at lower doses of the HAs from antigenically distinct influenza A virus H3 subtype strains. This finding supports the development of multivalent (such as bivalent, trivalent or quadrivalent) influenza vaccines including HAs from antigenically distinct influenza A viruses, such as HAs from antigenically distinct H3 subtype strains. The present disclosure provides an immunogenic composition comprising a first haemagglutinin (HA) from a first influenza A virus H3 subtype strain and a second HA from a second influenza A virus H3 subtype strain, wherein the second HA is antigenically distinct from the first HA, and wherein the immunogenic composition is capable of inducing a protective antibody response against other influenza A virus H3 subtype strains. The present disclosure also provides a method of preparing an immunogenic composition, the method comprising selecting a first haemagglutinin (HA) from a first influenza A virus H3 subtype strain and selecting a second HA from a second influenza A virus H3 subtype strain, wherein the second HA is antigenically distinct from the first HA, and wherein the immunogenic composition is capable of inducing a protective antibody response against other influenza A virus H3 subtype strains. The present disclosure also provides an immunogenic composition comprising: a first haemagglutinin (HA) from a first influenza A virus H3 subtype strain and a second HA from a second influenza A virus H3 subtype strain, wherein the second HA is antigenically distinct from the first HA; and a further HA selected from an influenza A virus strain of a H1, H2, H3, H5, H7, H9, or H10 subtype or a further HA selected from an influenza B virus, wherein the first HA and the second HA are each provided at a dose that is less than the dose of the further HA. The present disclosure also provides a vaccine comprising an immunogenic composition disclosed herein or an immunogenic composition prepared by a method disclosed herein, and a pharmaceutically acceptable carrier, diluent or excipient. The present disclosure also provides a method of treating and / or preventing an influenza- associated disease, disorder or condition in a subject, the method comprising administering a therapeutically effective amount of an immunogenic composition disclosed herein, an immunogenic composition prepared by a method disclosed herein, or a vaccine disclosed herein, to the subject. The present disclosure also provides the use of an immunogenic composition disclosed herein, an immunogenic composition prepared by a method of disclosed herein, or a vaccine disclosed herein, in the manufacture of a medicament for treating and / or preventing an influenza-associated disease, disorder or condition in a subject. The present disclosure also provides a container comprising a sterile liquid formulation of, or a lyophilised composition comprising, an immunogenic composition disclosed herein, an immunogenic composition prepared by a method of disclosed herein, or a vaccine disclosed herein. Particularly preferred embodiments are disclosed herein, including in the independent claims. Brief description of the drawings The following figures form part of the present specification and are included to further demonstrate certain embodiments of the present disclosure. The disclosure may be better understood by reference to one or more of these figures in combination with the detailed description of specific embodiments presented herein. It will be appreciated by persons skilled in the art that numerous variations and / or modifications may be made to the above-described embodiments, without departing from the broad general scope of the present disclosure. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive. Figure 1 is a schematic representation of (A) naïve ferrets receiving a prime-boost-boost vaccination regimen, (B) naïve ferrets receiving an adjuvanted prime-boost vaccination regimen, and (C) ferrets intranasally infected with an ancestral A(H3N2) influenza virus (A / Victoria / 182 / 1982 strain) prior to receiving a prime-boost-boost vaccination regimen. Figure 2 is a graphical representation of the HAI antibody titres raised against 30 μg of (A) an A / Victoria / 182 / 1982 strain, (B) an A / Kansas / 14 / 2017 strain, (C) an A / Perth / 20 / 2020 strain, (D) an A / Tasmania / 503 / 2020 strain, (E) an A / South Australia / 34 / 2019 strain, (F) an A / Hong Kong / 2671 / 2019 strain, (G) an A / Cambodia / e08263601 / 2020 strain, and (H) an A / Darwin / 6 / 2021 strain, in naïve ferrets receiving a prime-boost-boost vaccination regimen. Each symbol indicates a single animal; two ferrets per group. Circles represent vaccination using an A / South Australia / 34 / 2019 strain. Squares represent vaccination using an A / Kansas / 14 / 2017 strain. Triangles represent vaccination using a half dose (15 μg) of each an A / South Australia / 34 / 2019 strain and an A / Kansas / 14 / 2017 strain in combination. The dotted line indicates a HAI antibody titre of 20 (the limit of detection for the assay). Figure 3 is a graphical representation of the HAI antibodies titres raised against 30 μg of (A) an A / Victoria / 182 / 1982 strain, (B) an A / Kansas / 14 / 2017 strain, (C) an A / Perth / 20 / 2020 strain, (D) an A / Tasmania / 503 / 2020 strain, (E) an A / South Australia / 34 / 2019 strain, (F) an A / Hong Kong / 2671 / 2019 strain, (G) an A / Cambodia / e08263601 / 2020 strain, and (H) an A / Darwin / 6 / 2021 strain, in naïve ferrets receiving an adjuvanted prime-boost vaccination regimen. Each symbol indicates a single animal; two ferrets per group. Circles represent prime- boost using an A / South Australia / 34 / 2019 strain. Squares represent prime-boost using an A / Kansas / 14 / 2017 strain. The dotted line indicates a HAI antibody titre of 20 (the limit of detection for the assay). Figure 4 is a graphical representation of the HAI antibodies titres raised against 30 μg of (A) an A / Victoria / 182 / 1982 strain, (B) an A / Kansas / 14 / 2017 strain, (C) an A / Perth / 20 / 2020 strain, (D) an A / Tasmania / 503 / 2020 strain, (E) an A / South Australia / 34 / 2019 strain, (F) an A / Hong Kong / 2671 / 2019 strain, (G) an A / Cambodia / e08263601 / 2020 strain, and (H) an A / Darwin / 6 / 2021, in ferrets intranasally infected with an ancestral A(H3N2) influenza virus (A / Victoria / 182 / 1982 strain) prior to receiving a prime-boost-boost vaccination regimen. Each symbol indicates a single animal; two ferrets per group. Circles represent prime-boost-boost using an A / South Australia / 34 / 2019 strain. Squares represent prime-boost-boost using an A / Kansas / 14 / 2017 strain. Triangles represent prime-boost-boost using a half dose (15 μg) of each an A / South Australia / 34 / 2019 strain and an A / Kansas / 14 / 2017 strain in combination. The dotted line indicates a HAI antibody titre of 20 (the limit of detection for the assay). Figure 5 is a graphical representation of the HAI antibody titres in ferrets across all vaccination regimens. Each column provides results from an individual ferret in each vaccination regimen. Numerical values indicate HAI titres from two animals. (A) 2 weeks post prime; SA represents prime with an A / South Australia / 34 / 2019 strain. Kan represents prime using an A / Kansas / 14 / 2017 strain. SA+Kan represents prime using a half dose of each an A / South Australia / 34 / 2019 strain and an A / Kansas / 14 / 2017 strain in combination. (B) 4 weeks post prime; SA > SA represents prime-boost with an A / South Australia / 34 / 2019 strain. Kan > Kan represents prime-boost using A / Kansas / 14 / 2017. SA+Kan > SA+Kan represents prime-boost using a half dose (15 μg) of each an A / South Australia / 34 / 2019 strain and an A / Kansas / 14 / 2017 strain in combination. (C) 6 weeks post prime; SA > SA > SA represents prime-boost-boost with an A / South Australia / 34 / 2019 strain. Kan > Kan > Kan represents prime-boost-boost using A / Kansas / 14 / 2017. SA+Kan > SA+Kan > SA+KAn represents prime-boost-boost using a half dose (15 μg) of each an A / South Australia / 34 / 2019 strain and an A / Kansas / 14 / 2017 strain in combination. Figure 6 is a schematic representation of the phylogenetic diversity and distribution of influenza A virus H3N2 strains based on HA sequences. H3 viruses were classified into genetic clades, as indicated in the legend. This tree was generated by nextstrain.org and was accessed and copied from the Nextstrain website on 29 May 2023 (https: / / nextstrain.org / flu / seasonal / h3n2 / ha / 2y)

[0002] Detailed description General Techniques and Definitions Unless specifically defined otherwise, all technical and scientific terms used herein shall be taken to have the same meaning as commonly understood by one of ordinary skill in the art (e.g., in genomics, immunology, molecular biology, immunohistochemistry, biochemistry, oncology, and pharmacology). The present disclosure is performed using, unless otherwise indicated, conventional techniques of molecular biology, microbiology, recombinant DNA technology and immunology. Such procedures are disclosed, for example in Sambrook, Fritsch & Maniatis, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratories, New York, Fourth Edition (2012), whole of Vols I, II, and III; DNA Cloning: A Practical Approach, Vols. I and II (D. N. Glover, Second Edition., 1995), IRL Press, Oxford, whole of text; Oligonucleotide Synthesis: A Practical Approach (M. J. Gait, ed, 1984) IRL Press, Oxford, whole of text, and particularly the papers therein by Gait, ppl-22; Atkinson et al, pp35-81; Sproat et al, pp 83-115; and Wu et al, pp 135- 151; 4. Nucleic Acid Hybridization: A Practical Approach (B. D. Hames & S. J. Higgins, eds., 1985) IRL Press, Oxford, whole of text; Immobilized Cells and Enzymes: A Practical Approach (1986) IRL Press, Oxford, whole of text; Perbal, B., A Practical Guide to Molecular Cloning (1984) and Methods In Enzymology (S. Colowick and N. Kaplan, eds., Academic Press, Inc.), whole of series. Those skilled in the art will appreciate that the present disclosure is susceptible to variations and modifications other than those specifically disclosed. It is to be understood that the disclosure includes all such variations and modifications. The disclosure also includes all of the steps, features, compositions and compounds referred to or indicated in this specification, individually or collectively, and any and all combinations of any two or more of said steps or features. Thus, each feature of any particular example or embodiment of the present disclosure may be applied mutatis mutandis to any other example or embodiment of the present disclosure. The present disclosure is not to be limited in scope by the specific embodiments disclosed herein, which are intended for the purpose of exemplification only. Functionally equivalent products, compositions and methods are clearly within the scope of the disclosure, as disclosed herein. Throughout this specification, unless specifically stated otherwise or the context requires otherwise, reference to a single step, composition of matter, group of steps or group of compositions of matter shall be taken to encompass one and a plurality (i.e. one or more) of those steps, compositions of matter, groups of steps or group of compositions of matter. As used herein, the singular forms of “a”, “and” and “the” include plural forms of these words, unless the context clearly dictates otherwise. The term “and / or”, e.g., “X and / or Y” shall be understood to mean either “X and Y” or “X or Y” and shall be taken to provide explicit support for both meanings or for either meaning. Throughout this specification, the word “comprise” or variations such as “comprises” or “comprising” will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps. The term “about” in relation to a numerical value x is optional and means, for example, any number within 1, 5 or 10% of the referenced number. The term “about” also encompasses the exact number recited. Immunogenic compositions The inventors have surprisingly shown that an immunogenic composition comprising two HAs from antigenically distinct influenza A virus H3 subtype strains is capable of inducing a protective antibody response against other influenza A virus H3 subtype strains, and in particular a protective antibody response against subsequently emerging influenza A virus H3 subtype strains. Accordingly, the present disclosure provides an immunogenic composition comprising a first haemagglutinin (HA) from a first influenza A virus H3 subtype strain and a second HA from a second influenza A virus H3 subtype strain, wherein the second HA is antigenically distinct from the first HA, and wherein the immunogenic composition is capable of inducing a protective antibody response against other influenza A virus H3 subtype strains. The present disclosure also provides a method of preparing an immunogenic composition, the method comprising selecting a first haemagglutinin (HA) from a first influenza A virus H3 subtype strain and selecting a second HA from a second influenza A virus H3 subtype strain, wherein the second HA is antigenically distinct from the first HA, and wherein the immunogenic composition is capable of inducing a protective antibody response against other influenza A virus H3 subtype strains. The present disclosure also provides an immunogenic composition comprising: a first haemagglutinin (HA) from a first influenza A virus H3 subtype strain and a second HA from a second influenza A virus H3 subtype strain, wherein the second HA is antigenically distinct from the first HA; and a further HA selected from a influenza A virus strain of a H1, H2, H3, H5, H7, H9, or H10 subtype or a further HA selected from an influenza B virus, wherein the first HA and the second HA are each provided at a dose that is less than the dose of the further HA. As used herein, the term “immunogenic” will be understood to refer to a compound or composition that induces or generates an immune response. A compound or composition that induces or generates an immune response is typically one that induces a humoral or cell-mediated response in a subject to which the compound or composition is administered. The humoral or cell-mediated response may be specific to the compound or composition. Such a response may be detected and / or quantified by determining the induction of antibodies in the subject and / or cellular responses. A quantitative antibody measurement may be determined. Alternatively, or in addition, a qualitative antibody measurement may be determined. For example, but without limitation, a measure of one or more functional features of antibodies elicited in a subject to which the compound or composition is administered, may be determined. Suitable functional features which can be measured are known in the art and include, without limitation, hemagglutinin agglutination inhibition. A quantitative method for the determination of expression or secretion of cytokines or alteration in the phenotype of immune cells may also be used. The immune response may be a protective immune response. By “protective immune response” it is meant an immune response that is sufficient to prevent or at least reduce the severity or extent of one or more symptoms of an influenza-associated disease, disorder or condition in a subject. A protective immune response may be determined directly through experimentation (such as by performing challenge studies to a subject vaccinated with a particular compound or composition). Alternatively, or in addition, a protective immune response may be determined via a measurement of one or more suitable correlates of protection. Suitable correlates of protection will be appreciated by one of skill in the art, and may include, for example but without limitation, antibody binding titre, haemagglutination inhibition (HAI) titre, microneutralisation (MN) titre, cytokine assays, cellular responses and antibody dependent cellular cytotoxicity assays. A protective immune response may be demonstrated by a HAI titre of about 40, or about 50, or about 60 according to known, standard HAI assay protocols, including any of those disclosed herein. Thus, in one example, a protective immune response may be demonstrated by a HAI titre of about 40 according to known, standard HAI assay protocols, or according to any HAI assay protocols disclosed herein. As used herein, “immunise” and “immunisation” refer to administering the immunogenic composition to elicit or potentiate an immune response in a subject, such as a protective immune response to the immunogenic composition. The immunogenic compositions disclosed herein may comprise one or more viral proteins. Suitable influenza viral proteins include haemagglutinin (HA), neuraminidase (NA), matrix proteins (M1, M2, NB and BM2), a heterotrimeric RNA-dependent RNA polymerase (made up of one polymerase acidic subunit (PA), and two polymerase basic subunits (PB1 and PB2)), nucleoprotein (NP), and two non-structural proteins (NS1 and NS2; NS2 is also known as nuclear export protein (NEP)), and pro-apoptotic peptide (PB1-F2). Typically, the immunogenic compositions disclosed herein comprise HA and / or NA. Alternatively, or in addition, the immunogenic compositions disclosed herein may comprise one or more RNAs encoding one or more viral proteins. Suitably, the RNA may be a messenger RNA (mRNA) comprising a nucleotide sequence encoding a viral protein. For example, the immunogenic compositions disclosed herein may comprise one or more mRNAs encoding HA and / or NA. Thus, any reference herein to an immunogenic composition or vaccine comprising a first, second or further HA should be understood to include such compositions or vaccines wherein the first, second or further HA is provided in the form of an RNA encoding said first, second or further HA. As used herein, the term “RNA” or “ribonucleic acid” refers to a single stranded molecular chain of nucleotides chemically bonded by a series of ester linkages between the phosphoryl group of one nucleotide and the hydroxyl group of the sugar in an adjacent nucleotide. Suitable forms of RNA will be apparent to the skilled person, for example, monocistronic mRNA or multicistronic mRNA. The monocistronic mRNA or multicistronic mRNA may be conventional mRNA (cRNA) or a self-replicating RNA. Any suitable RNA constructs or vectors known in the art may be used in the context of the present disclosure to deliver viral proteins to a subject. The terms “haemagglutinin” (which is synonymous with “hemagglutinin”) and “HA” refer to any haemagglutinin protein known to those of skill in the art (e.g., influenza A virus HA subtypes of H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17, H18 and influenza B virus HA subtypes of B / Victoria-like or B / Yamagata-like). Influenza haemagglutinin (HA) is a glycoprotein encoded by the HA gene segment of an influenza virus. HA is typically expressed as a homotrimer on the surface of the viral capsid and is integral to its infectivity. To this end, HA allows for the recognition of cells in the upper respiratory tract or erythrocytes by binding to glycans thereon that contain the monosaccharide sialic acid. This leads to internalisation of the influenza virus by the cell into an endosome, which subsequently facilitates conformational rearrangement of the HA homotrimer. The HA protein then fuses with the endosomal membrane, thereby allowing for the release of viral gene segments, which are in the form of a ribonucleoprotein complex (RNP) together with nucleoproteins and a polymerase complex, into the cytoplasm of the host cell. The RNPs are transported into the host nucleus followed by transcription, and replication of the viral genome. The HA protein, together with the other newly generated viral proteins and a replicated genome, is then incorporated into the envelope of an influenza virion as it buds from an infected host cell. The HA protein on new viral particles remains attached to sialic acid groups of glycoproteins on the external cell surface and neuraminidase (NA) cleaves these groups and thereby allows for the efficient release of the newly formed virions. In the compositions disclosed herein containing two HA proteins (a first and a second HA protein), the second HA may be antigenically distinct from the first HA. As used herein, the term “antigenically distinct” will be understood to mean that one HA contains structural differences (such as differences in primary, secondary, tertiary and / or quaternary structure, including differences in glycosylation pattern) and / or functional differences (such as receptor binding specificity and / or glycosylation) to another HA. The extent of the structural and / or functional differences, and hence, the extent to which two HA proteins are structurally distinct, may vary. One HA protein may be determined as being antigenically distinct from another as measured using a haemagglutination inhibition (HAI) assay, including any HAI assay disclosed in the present description or in the Examples. HAI assays are well known in the art. Standard protocols for a HAI assay typically involve creating a dilution series of sera from human or non-human animals (e.g., ferrets) across a multi-well plate, such as a 96 well plate. A known amount of a virus is added to each well, and the plate is incubated for 30 minutes at room temperature. Red blood cells (RBCs) are then added and the plate incubated for a further 30-45 minutes at room temperature. If antibodies are present in the sera sample that cross-react with the virus, the antibodies will bind to the virus and prevent the virus from haemagglutinating the RBCs. Haemagglutination is determined by visual inspection by a person skilled in the art, or by using a robot whereby patterns of agglutination have been defined by a person skilled in the art. Virus neutralisation assays (including variations such as focus reduction assay and high-content imaging-based micro-neutralization Test (HINT) assay), may also be used. In this way, the exact titre of the antibodies in the sera can be determined. Useful references describing HAI assays in more detail include Pedersen, J.C. Methods in Molecular Biology, In: Spackman, E. (eds) Animal Influenza Virus, vol 1161, 2014; Webster R, Cox N, Stöhr K. WHO Animal Influenza Manual. WHO / CDS / CSR / NCS. 2002;2002.5:1–99; and WHO Global Influenza Surveillance Network. Manual for the laboratory diagnosis and virological surveillance of influenza, 2011, each of which are incorporated herein by reference. Alternatively, one HA protein may be determined as being antigenically distinct from another as measured using a microneutralisation (MN) assay. MN assays are well known in the art. A “HAI titre” of a sample is determined to be the inverse of the last / highest dilution of sera where RBCs were not agglutinated. HAI titres may be described as the antilog of the arithmetic mean of the log10-transformed titres (geometric mean titres (GMTs)). Accordingly, a HAI titre of about 32 to about 40 confers about 50% protection from homologous infection, and a HAI titre of about 160 to about 320 confers about 100% protection from homologous infection. One HA protein may be defined as being antigenically distinct from another HA protein by virtue of being a certain number of HAI units apart. As used herein, a “HAI unit” is a unit of antigenic distance that corresponds to a two-fold dilution of antiserum in the HAI assay. This sera can be ferret sera, human sera, or other antibodies directed to the HA protein e.g., monoclonal antibodies. In the case of serological assays, the antigenic difference may also be determined by a decrease in reactivity as exemplified by the World Health Organization (WHO) in a seasonal strain announcement. For example, a second HA may be four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, or eleven more HAI units apart from the first HA. The second HA may be at least four HAI units apart from the first HA. The HAI unit may be determined using a HAI assay. The second HA may be determined as being antigenically distinct from the first HA as measured using a HAI assay, wherein non-human animals (e.g., ferrets) are infected with a first HA from a first influenza A virus H3 subtype strain. After a period of time sufficient to develop antibodies against the first HA, blood is extracted from the non-human animals, sera is prepared and serially diluted. Equal volumes of each dilution point are combined with RBCs and the first HA from the first influenza A virus H3 subtype strain or a second HA from a second influenza A virus H3 subtype strain, and reactions are monitored for haemagglutination. The second HA may be considered to be antigenically distinct if it is four or more HAI units apart from the first HA. Serum generated following infection with the second HA may also be tested for reactivity to the first HA and a similar difference in reactivity observed. The immunogenic composition may be determined as being capable of inducing a protective antibody response against influenza A virus H3 subtype strains as measured using a HAI assay. Human studies have shown that HAI titres of human influenza virus are correlated with a protective immune response (Potter & Oxford (1979) Br Med Bull 35: 69-75). The influenza A virus H3 subtype strains referred to herein can be grouped into different genetic “clades” and “sub-clades”. An influenza clade is a subdivision of influenza viruses (beyond subtypes or lineages) based on the similarity of their HA gene sequences. Clades and sub-clades that are genetically different from others are not necessarily antigenically distinct. Clades and sub-clades of influenza viruses, including influenza A H3 subtype strains, are publicly known and consistently applied. For example, such clade and sub-clade taxonomies are provided by accessing the Nextstrain database (https: / / nextstrain.org / flu / seasonal / h3n2 / ha / 2y). Influenza A virus H3 subtype strains may be from clade 1, 2 or 3 (or any other categorisation nomenclature presented by the WHO to categorise clades as new strains emerge; thus, the strains may be from different clade categories as published by the WHO). An influenza A virus H3 subtype strain from clade 1 may be from subclade 1a or subclade 1a.1. An influenza A virus H3 subtype strain from clade 2 may be from subclade 2a, 2a.1, 2a.1a, 2a.1b, 2a.2, 2a.3, 2a.3a, 2a.3a.1, 2a.3b, 2b, 2c or 2d. An influenza A virus H3 subtype strain from clade 3 may be from subclade 3C.2a1, 3C.2a1a, 3C.2a1b.1, 3C.2a1b.1a, 3C.2a1b.1b, 3C.2a1b.2, 3C.2a1b.2a, 3C.2a1b.2b, 3C.2a2, 3C.2a3, 3C.3 or 3C.3a1. The immunogenic compositions or vaccines disclosed herein may be capable of providing cross- clade protection. As used herein, the phrase “cross-clade protection” is broadly defined as a protective immune response against influenza A virus H3 subtype strains from clades or subclades that are not present in the immunogenic composition or vaccine. For example, an immunogenic composition comprising a first HA from subclade 3C.2a1b.2a and a second HA from subclade 3C.3a1 may be capable of inducing a protective immune response against at least subclades 3C.2a1b.1b, 3C.2a1b.1, 3C.2a1b.1c, 3C.2a1.2a.1, 3C.2a1.2a.1a, 3C.2a1.2a.2a and combinations thereof. It will be understood by the skilled person that the immunogenic composition is also capable of inducing a protective immune response against influenza A virus H3 subtype strains that are present in the immunogenic composition (i.e., the homologous strain). The immunogenic composition disclosed herein may be capable of inducing a protective antibody response against influenza A virus H3 subtype strains in different (i.e., non homologous) sub- clades or clades. The immunogenic composition may be capable of inducing a protective antibody response against influenza A virus H3 subtype strains that emerge after an initial date of emergence of the first influenza A virus H3 subtype strain. The immunogenic composition may be capable of inducing a protective antibody response against influenza A virus H3 subtype strains that emerge after an initial date of emergence of the second influenza A virus H3 subtype strain. For example, the immunogenic composition may be capable of inducing a protective antibody response against influenza A virus H3 subtype strains that emerge after an initial date of emergence of the first influenza A virus H3 subtype strain and the second influenza A virus H3 subtype strain. The first HA and the second HA may be selected from different subclades of clade 3C.2a. For example, the first HA may be selected from subclade 3C.2a1b.2a and the second HA may be selected from subclade 3C.2a1b.1b. The first HA may be selected from subclade 3C.2a1b.2a and the second HA may be selected from subclade 3C.2a1b.1c. The first HA may be selected from subclade 3C.2a1b.2a and the second HA may be selected from subclade 3C.2a1.2a.1. The first HA may be selected from subclade 3C.2a1b.2a and the second HA may be selected from subclade 3C.2a1.2a.1a. The first HA may be selected from subclade 3C.2a1b.2a and the second HA may be selected from subclade 3C.2a1.2a.2a. The second HA may be selected from subclade 3C.2a1b.2a and the first HA may be selected from subclade 3C.2a1b.1b. The second HA may be selected from subclade 3C.2a1b.2a and the first HA may be selected from subclade 3C.2a1b.1c. The second HA may be selected from subclade 3C.2a1b.2a and the first HA may be selected from subclade 3C.2a1.2a.1. The second HA may be selected from subclade 3C.2a1b.2a and the first HA may be selected from subclade 3C.2a1.2a.1a. The second HA may be selected from subclade 3C.2a1b.2a and the first HA may be selected from subclade 3C.2a1.2a.2a. The first HA may be selected from subclade 3C.2a1b.1b and the second HA may be selected from subclade 3C.2a1b.1c. The first HA may be selected from subclade 3C.2a1b.1b and the second HA may be selected from subclade 3C.2a1.2a.1. The first HA may be selected from subclade 3C.2a1b.1b and the second HA may be selected from subclade 3C.2a1.2a.1a. The first HA may be selected from subclade 3C.2a1b.1b and the second HA may be selected from subclade 3C.2a1.2a.2a. The second HA may be selected from subclade 3C.2a1b.1b and the first HA may be selected from subclade 3C.2a1b.1c. The second HA may be selected from subclade 3C.2a1b.1b and the first HA may be selected from subclade 3C.2a1.2a.1. The second HA may be selected from subclade 3C.2a1b.1b and the first HA may be selected from subclade 3C.2a1.2a.1a. The second HA may be selected from subclade 3C.2a1b.1b and the first HA may be selected from subclade 3C.2a1.2a.2a. The first HA may be selected from subclade 3C.2a1b.1c and the second HA may be selected from subclade 3C.2a1.2a.1. The first HA may be selected from subclade 3C.2a1b.1c and the second HA may be selected from subclade 3C.2a1.2a.1a. The first HA may be selected from subclade 3C.2a1b.1c and the second HA may be selected from subclade 3C.2a1.2a.2a. The second HA may be selected from subclade 3C.2a1b.1c and the first HA may be selected from subclade 3C.2a1.2a.1. The second HA may be selected from subclade 3C.2a1b.1c and the first HA may be selected from subclade 3C.2a1.2a.1a. The second HA may be selected from subclade 3C.2a1b.1c and the first HA may be selected from subclade 3C.2a1.2a.2a. The first HA may be selected from subclade 3C.2a1.2a.1 and the second HA may be selected from subclade 3C.2a1.2a.1a. The first HA may be selected from subclade 3C.2a1.2a.1 and the second HA may be selected from subclade 3C.2a1.2a.2a. The second HA may be selected from subclade 3C.2a1.2a.1 and the first HA may be selected from subclade 3C.2a1.2a.1a. The second HA may be selected from subclade 3C.2a1.2a.1 and the first HA may be selected from subclade 3C.2a1.2a.2a. The first HA may be selected from subclade 3C.2a1.2a.1a and the second HA may be selected from subclade 3C.2a1.2a.2a. The second HA may be selected from subclade 3C.2a1.2a.1a and the first HA may be selected from subclade 3C.2a1.2a.2a. The first HA may be selected from subclade 3C.3a and the second HA may be selected from subclade 3C.2a. For example, the first HA may be selected from subclade 3C.3a1 and the second HA may be selected from subclade 3C.2a1b.2a. The first HA may be selected from subclade 3C.3a1 and the second HA may be selected from subclade 3C.2a1b.1b. The first HA may be selected from subclade 3C.3a1 and the second HA may be selected from subclade 3C.2a1b.1c. The first HA may be selected from subclade 3C.3a1 and the second HA may be selected from subclade 3C.2a1.2a.1. The first HA may be selected from subclade 3C.3a1 and the second HA may be selected from subclade 3C.2a1.2a.1a. The first HA may be selected from subclade 3C.3a1 and the second HA may be selected from subclade 3C.2a1.2a.2a. The first HA may be selected from clade 3C.2a and the second HA may be selected from 3C.3a For example, the first HA may be selected from subclade 3C.2a1b.2a and the second HA may be selected from subclade 3C.3a1. The first HA may be selected from subclade 3C.2a1b.1b and the second HA may be selected from subclade 3C.3a1. The first HA may be selected from subclade 3C.2a1b.1c and the second HA may be selected from subclade 3C.3a1. The first HA may be selected from subclade 3C.2a1.2a.1 and the second HA may be selected from subclade 3C.3a1. The first HA may be selected from subclade 3C.2a1.2a.1a and the second HA may be selected from subclade 3C.3a1. The first HA may be selected from subclade 3C.2a1.2a.2a and the second HA may be selected from subclade 3C.3a1. The influenza A virus H3 subtype strains of the present disclosure may contain the influenza A virus NA subtypes N1, N2, N3, N4, N5, N6, N7, N8 or N9. The influenza A virus H3 subtype strain may be of a N1, N2, N3, N4, N5, N6, N7, N8 or N9 subtype. The influenza A virus H3 subtype strain may be a strain selected from the group consisting of H3N1, H3N2 and H3N8. The first or the second influenza A virus H3 subtype strain may be a H3N2 strain. Alternatively, the first and the second influenza A virus H3 subtype strain may be a H3N2 strain. The first HA may be selected from an A / Kansas / 14 / 2017 / H3N2 strain and the second HA may be selected from an A / South Australia / 34 / 2019 / H3N2. The first HA may be selected from an A / Kansas / 14 / 2017 / H3N2 strain and the second HA may be selected from an A / Hong Kong / 2671 / 2019 / H3N2 strain. The first HA may be selected from an A / Kansas / 14 / 2017 / H3N2 strain and the second HA may be selected from an A / Perth / 20 / 2020 / H3N2 strain. The first HA may be selected from an A / Kansas / 14 / 2017 / H3N2 strain and the second HA may be selected from an A / Tasmania / 503 / 2020 / H3N2 strain. The first HA may be selected from an A / Kansas / 14 / 2017 / H3N2 strain and the second HA may be selected from an A / Cambodia / e08263601 / 2020 / H3N2 strain. The first HA may be selected from an A / Kansas / 14 / 2017 / H3N2 strain and the second HA may be selected from an A / Darwin / 6 / 2021 / H3N2 strain. The first HA may be selected from an A / South Australia / 34 / 2019 / H3N2 strain and the second HA may be selected from an A / Hong Kong / 2671 / 2019 / H3N2 strain. The first HA may be selected from an A / South Australia / 34 / 2019 / H3N2 strain and the second HA may be selected from an A / Perth / 20 / 2020 / H3N2 strain. The first HA may be selected from an A / South Australia / 34 / 2019 / H3N2 strain and the second HA may be selected from an A / Tasmania / 503 / 2020 / H3N2 strain. The first HA may be selected from an A / South Australia / 34 / 2019 / H3N2 strain and the second HA may be selected from an A / Cambodia / e08263601 / 2020 / H3N2 strain. The first HA may be selected from an A / South Australia / 34 / 2019 / H3N2 strain and the second HA may be selected from an A / Darwin / 6 / 2021 / H3N2 strain. The first HA may be selected from a A / Hong Kong / 2671 / 2019 / H3N2 strain and the second HA may be selected from an A / Perth / 20 / 2020 / H3N2 strain. The first HA may be selected from an A / Hong Kong / 2671 / 2019 / H3N2 strain and the second HA may be selected from an A / Tasmania / 503 / 2020 / H3N2 strain. The first HA may be selected from an A / Hong Kong / 2671 / 2019 / H3N2 strain and the second HA may be selected from an A / Cambodia / e08263601 / 2020 / H3N2 strain. The first HA may be selected from an A / Hong Kong / 2671 / 2019 / H3N2 strain and the second HA may be selected from an A / Darwin / 6 / 2021 / H3N2 strain. The first HA may be selected from an A / Perth / 20 / 2020 / H3N2 strain and the second HA may be selected from an A / Tasmania / 503 / 2020 / H3N2 strain. The first HA may be selected from an A / Perth / 20 / 2020 / H3N2 strain and the second HA may be selected from an A / Cambodia / e08263601 / 2020 / H3N2 strain. The first HA may be selected from an A / Perth / 20 / 2020 / H3N2 strain and the second HA may be selected from an A / Darwin / 6 / 2021 / H3N2 strain. The first HA may be selected from an A / Tasmania / 503 / 2020 / H3N2 strain and the second HA may be selected from an A / Cambodia / e08263601 / 2020 / H3N2 strain. The first HA may be selected from an A / Tasmania / 503 / 2020 / H3N2 strain and the second HA may be selected from an A / Darwin / 6 / 2021 / H3N2 strain. The first HA may be selected from an A / Cambodia / e08263601 / 2020 / H3N2 strain and the second HA may be selected from an A / Darwin / 6 / 2021 / H3N2 strain. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 1 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 2. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 1 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO:3. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 1 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO:4. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 1 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO:5. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 1 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO:6. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 1 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO:7. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 1 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO:8. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 2 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO:3. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 2 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO:4. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 2 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO:5. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 2 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO:6. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 2 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO:7. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 2 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO:8. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 3 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO:4. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 3 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO:5. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 3 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO:6. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 3 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO:7. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 3 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO:8. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 4 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO:5. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 4 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO:6. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 4 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO:7. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 4 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO:8. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 5 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO:6. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 5 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO:7. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 5 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO:8. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 6 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO:7. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 6 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO:8. The first HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO: 7 and the second HA may be encoded by a nucleotide comprising or consisting of the sequence set forth in SEQ ID NO:8. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 9 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 10. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 9 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 11. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 9 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 12. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 9 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 13. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 9 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 14. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 9 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 15. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 9 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 16. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 10 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 11. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 10 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 12. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 10 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 13. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 10 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 14. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 10 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 15. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 10 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 16. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 11 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 12. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 11 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 13. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 11 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 14. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 11 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 15. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 11 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 16. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 12 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 13. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 12 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 14. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 12 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 15. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 12 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 16. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 13 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 14. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 13 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 15. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 13 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 16. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 14 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 15. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 14 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 16. The first HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 15 and the second HA may comprise or consist of an amino acid sequence set forth in SEQ ID NO: 16. Influenza virus strains for use in seasonal vaccines change from season to season. Authorities such as the WHO publish a list of the predominant circulating influenza strains each year and further publish recommended influenza strains for inclusion in influenza vaccines, or reference strains to guide selection of the strains for inclusion in influenza vaccines. Accordingly, the first HA from the first influenza A virus H3 subtype strain may be recommended for inclusion in an immunogenic composition by a public health authority (e.g., the WHO). The second HA may then be selected from an H3 subtype strain that is antigenically distinct from the first HA. The extent to which the second HA is antigenically distinct from the first HA may be selected with the intention of providing a desired extent of breadth of protection against other influenza strains. The first HA and / or the second HA may be derived from a seasonal influenza virus strain (such as a seasonal H1 strain or a seasonal B / Victoria-like strain). As used herein, the term “seasonal influenza virus strain” refers to a strain of influenza virus to which a subject population is exposed to on a seasonal basis. The immunogenic composition disclosed herein may be suitable for protecting against seasonal virus strains that are presently being spread or are endemic within a human population. In addition, the immunogenic composition disclosed herein may be suitable for protecting against emerging seasonal virus strains. The first HA and / or the second HA may be derived from a pandemic influenza virus strain. Thus, where there is reference herein to a H3 strain (and an H3 HA), another aspect of this disclosure provides equivalent compositions and methods that are based on other influenza subtypes, including from pandemic strains. In addition, the immunogenic composition disclosed herein may further include one or more HA from a pandemic strain, in addition to first and second HAs from H3 subtype strains. As used herein, the term “pandemic influenza virus strain” refers to a strain of influenza virus being associated or susceptible to be associated with an outbreak of influenza disease. Generally, the characteristics of an influenza strain that give it the potential to cause a pandemic outbreak are: (a) it contains a new haemagglutinin compared to the haemagglutinins in currently-circulating human strains, i.e., one that has not been evident in the human population for over a decade (e.g., H2), or has not previously been seen at all in the human population (e.g., H5, H6 or H9, that have generally been found only in bird populations), such that the human population will be immunologically naïve to the strain’s haemagglutinin; (b) it is capable of being transmitted horizontally in the human population; and (c) it is pathogenic to humans. As such, the immunogenic composition disclosed herein may be suitable for protecting against potential pandemic virus strains that can or have spread from a non-human animal population to humans. The immunogenic composition of the present disclosure may comprise at least one or at least two additional strains of influenza virus (e.g., they may be trivalent or quadrivalent compositions). The immunogenic composition may comprise an additional influenza A virus strain. Alternatively, or in addition, the immunogenic composition may comprise an influenza B virus strain. For example, the immunogenic composition may comprise an additional influenza A virus strain and an influenza B virus strain. By way of example, the additional influenza A virus strain may include a HA selected from a H1, H2, H3, H5, H7, H9, or H10 subtype. The influenza A virus strain may be an influenza A virus H1 subtype strain. The influenza A virus strain may be selected from the group consisting of H1N1, H1N2, H2N2, H3N1, H3N2, H3N8 strains. In For example, the influenza A virus strain may be an influenza A virus H1N1 strain. The immunogenic composition may comprise an influenza B virus strain. For example, an influenza B virus strain of the B / Victoria-like lineage. Thus, the immunogenic composition disclosed herein may be a quadrivalent composition comprising a first and second HA derived from two H3N2 strains, an additional HA derived from a H1N1 strain, and an additional HA derived from a B / Victoria-like strain. The immunogenic composition may comprise HAs from at least three different strains of influenza virus. Thus, the immunogenic composition may be a trivalent composition. For example, the immunogenic composition may comprise HAs from two influenza A virus strains and one influenza B virus strain. The immunogenic composition may comprise two antigenically distinct HAs from an H3 virus strain and a HA from an influenza B virus strain. More particularly, the immunogenic composition may comprise a HA from an H3N1 strain, a HA from an H3N2 strain, and a HA from an influenza B virus strain of the Victoria lineage. The immunogenic composition may comprise a HA from an H1 virus strain, a HA from an H3 virus strain, and a HA from an influenza B virus strain. More particularly, the immunogenic composition may comprise a HA from an H1N1 strain, a HA from an H3N2 strain, and a HA from an influenza B virus strain of the Victoria lineage. The immunogenic composition may comprise HAs from at least four different strains of influenza virus. Thus, the immunogenic composition may be a quadrivalent composition. For example, the immunogenic composition may comprise HAs from three influenza A virus strains and one influenza B virus strain. The immunogenic composition may comprise a HA from an H1 virus strain, a HA from an influenza B virus strain, and two antigenically distinct HAs from an H3 virus strain. More particularly, the immunogenic composition may comprise a HA from an H1N1 strain, a HA from an influenza B virus strain of the Victoria lineage and two antigenically distinct HAs from an H3N2 strain. The immunogenic composition may comprise a first HA selected from a first influenza A virus H3 subtype strain, a second HA selected from a second influenza A virus H3 subtype strain, a further HA selected from an influenza A virus H1 strain and further HA selected from an influenza B virus. The immunogenic composition may comprise a first HA selected from a first influenza A virus H3N2 strain, a second antigenically distinct HA selected from a second influenza A virus H3N2 strain, a further HA selected from an influenza A virus H1N1 strain and further HA selected from an influenza B virus of the Victoria lineage. The immunogenic composition may comprise a first HA selected from an A / Kansas / 14 / 2017 / H3N2 strain, a second antigenically distinct HA selected from an A / South Australia / 34 / 2019 / H3N2 strain, a third HA selected from an influenza A virus H1N1 strain and fourth HA selected from an influenza B virus of the B / Victoria-like lineage. Haemagglutinin (HA) is the main immunogen in current inactivated influenza compositions, and doses are typically standardised by reference to HA levels. Typically, “standard dose” influenza compositions contain about 15 μg of HA per strain in each dosage form. Thus, “low dose” influenza compositions may contain less than about 15 μg of HA per strain in each dosage form, for example, about 12 μg, about 9 μg, about 7.5 μg, about 5 μg, or about 3.75 μg in each dosage form. “High” dose influenza compositions may contain more than about 15 μg of HA per strain in each dosage form, for example, about 30 μg, about 45 μg, about 60 μg, about 65 μg, about 70 μg, about 75 μg, about 80 μg, about 85 μg or about 90 μg in each dosage form. In this respect, the inventors have unexpectedly shown that immunogenic compositions comprising low doses of at least two antigenically distinct HAs from H3 subtype strains are capable of inducing a protective antibody response against other influenza A virus H3 subtype strains. The immunogenic composition disclosed herein may comprise less than 30 μg of the first HA from the first influenza A virus H3 subtype strain and less than 30 μg of the second HA from the second influenza A virus H3 subtype strain. The immunogenic composition may comprise about 15 μg of the first HA from the first influenza A virus H3 subtype strain and about 15 μg of the second HA from the second influenza A virus H3 subtype strain. For example, the immunogenic composition may comprise 15 μg of the first HA from the first influenza A virus H3 subtype strain and 15 μg of the second HA from the second influenza A virus H3 subtype strain. Thus, for example, the immunogenic composition may comprise about 7.5 μg of the first HA from the first influenza A virus H3 subtype strain and about 7.5 μg of the second HA from the second influenza A virus H3 subtype strain. Accordingly, the immunogenic composition may comprise 7.5 μg of the first HA from the first influenza A virus H3 subtype strain and 7.5 μg of the second HA from the second influenza A virus H3 subtype strain. Alternatively, the immunogenic composition may comprise about 30 μg of the first HA from the first influenza A virus H3 subtype strain and about 30 μg of the second HA from the second influenza A virus H3 subtype strain. In other alternative, the immunogenic composition may comprise about 45 μg of the first HA from the first influenza A virus H3 subtype strain and about 45 μg of the second HA from the second influenza A virus H3 subtype strain. In other alternatives, the immunogenic composition may comprise about 60 μg of the first HA from the first influenza A virus H3 subtype strain and about 60 μg of the second HA from the second influenza A virus H3 subtype strain. Higher doses are useful for vaccinating particular patient populations, such as the elderly (e.g., 50 years old and above, or 60 years old and above, or 65 years old and above), or infants (e.g., 16 years old and below, or below 18 years of age, or below 5 years of age, or below 2 years of age). In each immunogenic composition comprising different dosages of the HAs, the immunogenic compositions comprising those HAs at those dosages may also include one or more further HAs as disclosed herein, which further HAs may be provided at standard doses (e.g., about 15 μg). The immunogenic composition may comprise about 7.5 μg of the first HA from the first influenza A virus H3 subtype strain, about 7.5 μg of the second HA from the second influenza A virus H3 subtype strain and about 15 μg of HA from the additional strain of influenza virus. Alternatively, the immunogenic composition may comprise about 7.5 μg of the first HA, about 7.5 μg of the second HA and about 15 μg of HA per strain from two additional strains of influenza virus. For example, the immunogenic may comprise about 7.5 μg of the first HA from the first influenza A virus H3 subtype strain, about 7.5 μg of the second HA from the second influenza A virus H3 subtype strain, about 15 μg of the HA from the influenza A virus H1 strain, and about 15 μg of the HA from the influenza B virus of the Victoria lineage. The concentration of the first and the second HA may differ so long as they remain “low dose” (e.g., less than 15 μg of HA per dosage form). Typically, the concentration of the first and the second HA is a “low dose”, while the further HA from the additional influenza strain(s) is a “standard dose”. For example, the first HA and the second HA are each provided at half the dose of the further HA(s). The first HA and the second HA may each be provided at 7.5 μg and the further HA(s) may be provided at 15 μg. Suitably, the further HA is selected from an influenza A virus strain of a H1, H2, H3, H5, H7, H9, or H10 subtype and is provided at about 15 μg. The further HA selected from an influenza B virus may be provided at about 15 μg. The first HA and the second HA may be each provided at a dose that is less than the dose of the further HA. For example, the first and the second HA may be each provided at 7.5 μg and the further HA(s) may be each provided at 15 μg. The first and the second HA may be each provided at 15 μg and the further HA(s) may be each provided at 30 μg. The immunogenic composition may be prepared by a method comprising: (a) isolating a circulating influenza A virus H3 subtype strain; (b) antigenic analysis of the isolated circulating influenza A virus H3 subtype strain; and (c) selection of an antigenically distinct influenza A virus H3 subtype strain. For example, antigenic analysis may comprise the use of a HAI assay. Vaccines The present disclosure envisages that the immunogenic composition and / or the immunogenic composition produced according to the methods disclosed herein may be utilised in vaccine compositions. Influenza vaccines are generally based either on a live attenuated virus, an inactivated virus, recombinantly expressed proteins or mRNAs encoding influenza viral proteins. Inactivated vaccines may be based on whole virions, “split” virions, or on purified surface antigens. Antigens can also be presented in the form of virosomes. The present methods can be used for manufacturing any of these types of vaccine. Where an inactivated influenza virus is used, the vaccine may comprise whole virion, split virion, or purified surface antigens (e.g., hemagglutinin and optionally neuraminidase). Chemical means for inactivating a virus include treatment with an effective amount of one or more of the following inactivating agents: detergents, formaldehyde, b-propiolactone, methylene blue, psoralen, carboxyfullerene (C60), binary ethylamine, acetyl ethyleneimine, or combinations thereof. Non-chemical methods of viral inactivation are also known in the art, such as UV light or gamma irradiation. Virions can be harvested from virus-containing fluids, such as cell culture supernatant or egg allantoic fluid, by various methods such as those disclosed in, for example, WO2007 / 052055 and WO2009 / 115917, both of which are incorporated herein by reference. For example, a purification process may involve zonal centrifugation using a linear sucrose gradient solution (that optionally includes detergent to disrupt the virions) or affinity chromatography methods. Antigens may then be purified, after optional dilution, by diafiltration. In accordance with examples of the present disclosure where the immunogenic and / or vaccine composition comprises RNAs encoding influenza viral proteins, the RNA may be encapsulated in, bound to or adsorbed on a liposome, a lipid nanoparticle, a polymeric microparticle, or an oil- in-water emulsion. For example, the RNA may be mRNA. The immunogenic and / or vaccine composition may contain a pharmaceutically-acceptable carrier, diluent or excipient. By “pharmaceutically-acceptable carrier, diluent or excipient” is meant a solid or liquid filler, diluent or encapsulating substance that may be safely used in systemic administration. Depending upon the particular route of administration, a variety of carriers, diluent and excipients well known in the art may be used. These may be selected from a group including sugars, starches, cellulose and its derivatives, malt, gelatine, talc, calcium sulfate, vegetable oils, synthetic oils, polyols, alginic acid, phosphate buffered solutions, emulsifiers, isotonic saline and salts such as mineral acid salts including hydrochlorides, bromides and sulfates, organic acids such as acetates, propionates and malonates, water and pyrogen-free water. A useful reference describing acceptable carriers, diluents and excipients is Remington’s Pharmaceutical Sciences (Mack Publishing Co. N.J. USA, 1991) which is incorporated herein by reference. For the purposes of eliciting an immune response, certain immunological or immunogenic agents may be used in combination with the immunogenic composition of the present disclosure. The term “immunogenic agent” includes within its scope carriers, delivery agents, immunostimulants and / or adjuvants as are well known in the art. Thus, the immunogenic compositions and / or vaccines disclosed herein may comprise an adjuvant. As will be understood in the art, immunostimulants and adjuvants refer to or include one or more substances that enhance the immunogenicity and / or efficacy of a composition. Non-limiting examples of suitable immunostimulants and adjuvants include squalane and squalene (or other oils of plant or animal origin), inclusive of squalene oil-in-water emulsions (e.g., MF59, AS03 and AF03); block copolymers; TLR agonists, such as pathogen-derived compounds, including lipopeptides, glycolipids, nucleotides, small-molecule inhibitors and bacterial-derived components, such as flagellin; detergents such as Tween®-80; Quil® A, mineral oils such as Drakeol or Marcol, vegetable oils such as peanut oil; Corynebacterium-derived adjuvants such as Corynebacterium parvum; Propionibacterium-derived adjuvants such as Propionibacterium acne; Mycobacterium bovis (Bacille Calmette and Guerin or BCG); Bordetella pertussis antigens; tetanus toxoid; diphtheria toxoid; surface active substances such as hexadecylamine, octadecylamine, octadecyl amino acid esters, lysolecithin, dimethyldioctadecylammonium bromide, N,N-dicoctadecyl-Nc, Ncbis(2-hydroxyethyl-propanediamine), methoxyhexadecylglycerol, and pluronic polyols; polyamines such as pyran, dextransulfate, poly IC carbopol; peptides such as muramyl dipeptide and derivatives, dimethylglycine, tuftsin; oil emulsions; and mineral gels such as aluminium phosphate, aluminium hydroxide or alum; interleukins such as interleukin 2 and interleukin 12; monokines such as interleukin 1; tumour necrosis factor; interferons such as gamma interferon; immunostimulatory DNA such as CpG DNA, combinations such as saponin-aluminium hydroxide or Quil-A aluminium hydroxide; saponins, such as Matrix-M; liposomes; ISCOM® and ISCOMATRIX® adjuvant; mycobacterial cell wall extract; synthetic glycopeptides such as muramyl dipeptides or other derivatives; Avridine; Lipid A derivatives; dextran sulfate; DEAE-Dextran alone or with aluminium phosphate; carboxypolymethylene such as Carbopol' EMA; acrylic copolymer emulsions such as Neocryl A640 (e.g., U.S. Pat. No.5,047,238); water in oil emulsifiers such as Montanide ISA 720; poliovirus, vaccinia or animal poxvirus proteins; or mixtures thereof. Preferably, the adjuvant is MF59. Immunogenic agents may include carriers such as thyroglobulin; albumins such as human serum albumin; toxins, toxoids or any mutant cross-reactive material (CRM) of the toxin from tetanus, diphtheria, pertussis, Pseudomonas, E. coli, Staphylococcus, and Streptococcus; polyamino acids such as poly(lysine:glutamic acid); influenza; Rotavirus VP6, Parvovirus VP1 and VP2; hepatitis B virus core protein; hepatitis B virus recombinant vaccine and the like. Alternatively, a fragment or epitope of a carrier protein or other immunogenic protein may be used. For example, a T cell epitope of a bacterial toxin, toxoid or CRM may be used. In this regard, reference may be made to U.S. Patent No 5,785,973 which is incorporated herein by reference. Oil-in-water emulsions have been found to be particularly suitable for use in adjuvanting influenza virus vaccines. Various such emulsions are known, and they typically include at least one oil and at least one surfactant, with the oil(s) and surfactant(s) being biodegradable (metabolisable) and biocompatible. The oil droplets in the emulsion are generally less than 5 ^m in diameter, and may even have a sub-micron diameter, with these small sizes being achieved with a microfluidiser to provide stable emulsions. Droplets with an average size less than 220 nm are preferred as they can be subjected to filter sterilization. Suitable methods of manufacturing oil-in-water emulsion adjuvants for vaccines are disclosed, for example, in WO2006 / 100110 and WO2011 / 067672, both of which are incorporated herein by reference. The oil-in-water emulsion may be uniform. A uniform emulsion is characterized in that a majority of droplets (particles) dispersed therein is within a specified size range (e.g., in diameter). A suitable specified size range can be, for example, between 50-220 nm (e.g., 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220 nm or any range therein), between 50-180 nm, between 80-180 nm, between 100-175 nm, between 120-185 nm, between 130-190 nm, between 135-175 nm, between 150-175 nm. The uniform emulsion may contain <10% of the number of droplets (particles) that are outside of the specified range of diameters. The mean particle size of oil droplets in the oil-in-water emulsion preparation may be between 135-175 nm, e.g., 155 nm ± 20 nm as measured by dynamic light scattering, and such a preparation contains not more than 1 x 107large particles per mL of the preparation, as measured by optical particle sensing. “Large particles” as used herein mean those having diameters ^1.2 ^m, typically between 1.2- 400 ^m. The uniform emulsion may contain less than 10%, less than 5%, or less than 3% of the droplets that fall outside of the preferred size range. The mean droplet size of particles in an oil- in-water emulsion preparation may be between 125-185 nm, e.g., about 130 nm, about 140 nm, about 150 nm, about 155 nm, about 160 nm, about 170 nm, or about 180 nm, and the oil-in-water emulsion is uniform in that less than 5% of the number of droplets in the preparation fall outside the 125-185 nm range. The immunogenic and / or vaccine composition of the present disclosure can be used with oils, such as those from an animal (such as fish) or vegetable source. Sources for vegetable oils include, but are not limited to, nuts, seeds and grains. Peanut oil, soybean oil, coconut oil, and olive oil, the most commonly available, exemplify the nut oils. Jojoba oil obtained from the jojoba bean may also be used. Seed oils include, but are not limited to, safflower oil, cottonseed oil, sunflower seed oil, sesame seed oil and the like. In the grain group, corn oil is the most readily available, but the oil of other cereal grains such as wheat, oats, rye, rice, teff, triticale and the like may also be used. 6-10 carbon fatty acid esters of glycerol and 1,2- propanediol, while not occurring naturally in seed oils, may be prepared by hydrolysis, separation and esterification of the appropriate materials starting from the nut and seed oils. Fats and oils from mammalian milk are metabolisable and may therefore be used in the immunogenic and / or vaccine composition disclosed herein. The procedures for separation, purification, saponification and other means necessary for obtaining pure oils from animal sources are well known in the art. Most fish contain metabolisable oils which may be readily recovered. For example, cod liver oil, shark liver oil, and whale oil, such as spermaceti, exemplify several of the fish oils which may be used herein. A number of branched chain oils are synthesized biochemically in 5-carbon isoprene units and are generally referred to as terpenoids. Shark liver oil contains a branched, unsaturated terpenoid known as squalene, 2,6,10,15,19,23-hexamethyl-2,6,10,14,18,22-tetracosahexaene. Squalane, the saturated analog to squalene, may also be utilised in the present immunogenic and / or vaccine composition. Fish oils, including squalene and squalane, are readily available from commercial sources or may be obtained by methods known in the art such as for example, as disclosed in WO2011 / 141819, incorporated herein by reference. Other suitable oils are the tocopherols. Mixtures of oils are also envisaged. Surfactants can be classified by their ‘HLB’ (hydrophile / lipophile balance). Suitably, surfactants disclosed herein have a HLB of at least 10, more particularly at least 15, and even more particularly at least 16. The immunogenic and / or vaccine composition may include one or more surfactants including, but not limited to: the polyoxyethylene sorbitan esters surfactants (commonly referred to as the Tweens), especially polysorbate 20 and polysorbate 80; copolymers of ethylene oxide (EO), propylene oxide (PO), and / or butylene oxide (BO), sold under the DOWFAX™ tradename, such as linear EO / PO block copolymers; octoxynols, which can vary in the number of repeating ethoxy (oxy-l,2-ethanediyl) groups, with octoxynol-9 (Triton X-100, or t- octylphenoxypolyethoxyethanol); (octylphenoxy)polyethoxy ethanol (IGEPAL CA-630 / NP- 40); phospholipids such as phosphatidylcholine (lecithin); polyoxyethylene fatty ethers derived from lauryl, cetyl, stearyl and oleyl alcohols (known as Brij surfactants), such as triethyleneglycol monolauryl ether (Brij 30); and sorbitan esters (commonly known as the SPANs), such as sorbitan trioleate (Span 85) and sorbitan monolaurate. Non-ionic surfactants are preferred. Exemplary surfactants for including in the emulsion are Tween 80 (polyoxyethylene sorbitan monooleate), Span 85 (sorbitan trioleate), lecithin and Triton X-100. Mixtures of surfactants can also be used (e.g., Tween 80 / Span 85 mixtures). A combination of a polyoxyethylene sorbitan ester, such as polyoxyethylene sorbitan monooleate (Tween 80) and an octoxynol, such as t-octylphenoxypolyethoxyethanol (Triton X-100) is also suitable. Another envisaged combination comprises laureth 9 plus a polyoxyethylene sorbitan ester and / or an octoxynol. Exemplary amounts of surfactants (% by weight) are: polyoxyethylene sorbitan esters (such as Tween 80) 0.01% to 1%, in particular about 0.1%; octyl- or nonylphenoxy polyoxyethanols (such as Triton X-100, or other detergents in the Triton series) 0.001% to 0.1 %, in particular 0.005% to 0.02%; polyoxyethylene ethers (such as laureth 9) 0.1% to 20 %, more particularly 0.1% to 10 % and even more particularly 0.1% to 1 % or about 0.5%. The oil-in-water emulsions may be squalene-in-water emulsions, and more particularly, submicron squalene-in-water emulsions. Any suitable procedure is contemplated for producing immunogenic and / or vaccine compositions. Exemplary procedures include, for example, those disclosed in New Generation Vaccines (1997, Levine et al., Marcel Dekker, Inc. New York, Basel, Hong Kong), which is incorporated herein by reference. Any safe route of administration may be employed, including oral, rectal, parenteral, sublingual, buccal, intravenous, intra-articular, intra-muscular, intra-dermal, subcutaneous, inhalational, intranasal, intraocular, intraperitoneal, intracerebroventricular, topical, mucosal and transdermal administration, although without limitation thereto. Dosage forms include tablets, dispersions, suspensions, injections, solutions, syrups, troches, capsules, nasal sprays, suppositories, aerosols, transdermal patches and the like. These dosage forms may also include injecting or implanting controlled releasing devices designed specifically for this purpose or other forms of implants modified to act additionally in this fashion. Controlled release may be affected by coating with hydrophobic polymers including acrylic resins, waxes, higher aliphatic alcohols, polylactic and polyglycolic acids and certain cellulose derivatives such as hydroxypropylmethyl cellulose. In addition, the controlled release may be affected by using other polymer matrices, liposomes and / or microspheres. Compositions may be presented as discrete units such as capsules, sachets, pre-filled syringes, vials, ampoules, functional foods / feeds or tablets each containing a pre-determined amount of one or more therapeutic agents of the disclosure, as a powder or granules or as a solution or a suspension in an aqueous liquid, a non-aqueous liquid, an oil-in-water emulsion or a water-in-oil liquid emulsion. Such compositions may be prepared by any of the methods of pharmacy but all methods include the step of bringing into association one or more agents as disclosed above with the carrier which constitutes one or more necessary ingredients. In general, the compositions are prepared by uniformly and intimately admixing the agents of the disclosure with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product into the desired presentation. The above compositions may be administered in a manner compatible with the dosage formulation, and in such amount as effective. The dose administered to a subject, in the context of the present disclosure, should be sufficient to affect a beneficial response in a subject over an appropriate period of time (e.g., generate a protective immune response). The quantity of agent(s) to be administered may depend on the subject to be treated inclusive of the age, sex, weight and general health condition thereof, factors that will depend on the judgement of the practitioner. The immunogenic and / or vaccine compositions of the present disclosure may further comprise a buffer. The buffer may be any suitable buffer known in the art. For example, the buffer may be a TRIS, acetate, glutamate, lactate, maleate, tartrate, phosphate, citrate, carbonate, glycinate, histidine, glycine, succinate and triethanolamine buffer, phosphate buffer. The buffer may be a phosphate buffer. Alternatively, the buffer may be a succinate buffer. The buffer may be a histidine buffer. The buffer may be a citrate buffer. The buffer may be selected from US Pharmacopeia (USP) compatible buffers for parenteral use, in particular, when the vaccine is for parenteral use. For example the buffer may be selected from the group consisting of monobasic acids such as acetic, benzoic, gluconic, glyceric and lactic; dibasic acids such as aconitic, adipic, ascorbic, carbonic, glutamic, malic, succinic and tartaric, polybasic acids such as citric and phosphoric; and bases such as ammonia, diethanolamine, glycine, triethanolamine, and TRIS. Also disclosed herein is a container comprising a sterile liquid formulation of, or a lyophilised composition comprising, the immunogenic composition disclosed herein, an immunogenic composition prepared by the method disclosed herein, or the vaccine disclosed. Any suitable container known in the art may be used. For example, the container may be selected from the group consisting of a vial, a syringe, an ampoule, a flask, a fermentor, a bioreactor, a bag, a jar, an ampoule, a cartridge and a disposable pen. The container may be a syringe, vial or ampoule. The container may be made of glass, metals (e.g., steel, stainless steel, aluminium, etc.) and / or polymers (e.g., thermoplastics, elastomers, thermoplastic-elastomers). The container may be at least partially siliconized. These containers should be sterile. A kit or composition may be packaged (e.g., in the same box) with a leaflet including details of the immunogenic composition or vaccine e.g., instructions for administration, details of the antigens within the vaccine, etc. The instructions may also contain warnings e.g., to keep a solution of adrenaline readily available in case of anaphylactic reaction following vaccination, etc. Methods of treatment and prevention The influenza virus proteins and the immunogenic and / or vaccine compositions of the present disclosure may be suitable for administration to human or non-human animal subjects, such that the present disclosure provides methods of raising an immune response and / or treating and / or preventing an influenza-associated disease, disorder or condition in a subject. The present disclosure also provides a composition as disclosed herein for use as a medicament and provides the use of such a composition for the manufacture of a medicament for raising an immune response and / or preventing and / or treating an influenza-associated disease, disorder or condition in a subject. The present disclosure provides a method of treating and / or preventing an influenza-associated disease, disorder or condition in a subject, the method comprising administering a therapeutically effective amount of the immunogenic composition, an immunogenic composition prepared by the method disclosed herein or the vaccine disclosed herein, to the subject. The present disclosure also provides a method of eliciting an immune response in a subject, said method including the step of administering a therapeutically effective amount of the immunogenic composition, an immunogenic composition prepared by the method disclosed herein or the vaccine composition provided herein to the subject to thereby elicit the immune response in the subject. The present disclosure also provides the use of the immunogenic composition, an immunogenic composition prepared by the method disclosed herein or the vaccine disclosed herein in the manufacture of a medicament for treating and / or preventing an influenza-associated disease, disorder or condition in a subject. The present disclosure also provides the immunogenic composition, an immunogenic composition prepared by the method disclosed herein or the vaccine disclosed herein for use in treating and / or preventing an influenza-associated disease, disorder or condition in a subject. As disclosed herein, the term “subject”, “patient” and “individual” includes, but is not limited to, mammals, inclusive of humans, performance animals (such as horses, camels, greyhounds), livestock (such as cows, sheep, horses) and companion animals (such as cats and dogs). For example, the subject may be a human. By “raise an immune response” or “elicit an immune response” it is meant generate or stimulate the production or activity of one or more elements of the immune system inclusive of the cellular immune system, humoral immune system (i.e., antibodies) and / or the native immune system. The immune response disclosed herein may include one or more elements of the immune system, such as T lymphocytes, B lymphocytes, antibodies, neutrophils, dendritic cells inclusive of plasmacytoid dendritic cells, cytokines and / or chemokines. Non-limiting examples of cytokines include pro-inflammatory cytokines such as TNF-Į, IL-2, IL-6, IL-8, IL-17A and IL-1 (e.g., IL- 1ȕ). A non-limiting example of a chemokine is the neutrophil chemo-attractant IL-8. For example, the immune response that is elicited by the vaccine compositions disclosed herein is protective. The term “therapeutically effective amount” is the quantity which, when administered, at least partly ameliorates, eliminates or reduces a symptom or pathological sign of an influenza- associated disease, disorder or condition, such as an influenza infection. Alternatively, a therapeutically effective amount is a quantity which, when administered prevents the exacerbation of one or more symptoms or pathological signs of an influenza-associated disease, disorder or condition, such as an influenza infection. The amount to be administered will depend on the characteristics of the subject, such as general health, other diseases, age, sex, genotype, and body weight. A person skilled in the art will be able to determine appropriate dosages depending on these and other factors. Accordingly, this term is not to be construed to limit the present disclosure to a specific quantity, e.g., weight or amount of compound. As generally used herein, the terms “immunise”, “vaccinate” and “vaccine” refer to methods and / or compositions that are capable of eliciting a protective immune response against an influenza virus, whereby subsequent infection by the influenza virus, or a related subtype, strain or variant, is at least partly prevented or minimised. As used herein, “treating”, “treat” or “treatment” refers to a therapeutic intervention that at least partly ameliorates, eliminates or reduces a symptom or pathological sign of an influenza- associated disease, disorder or condition, such as an influenza infection, after it has begun to develop. Treatment need not be absolute to be beneficial to the subject. The beneficial effect can be determined using any methods or standards known to the ordinarily skilled artisan. A “prophylactic” treatment is a treatment administered to a subject who does not exhibit signs of the disease, disorder or condition, or exhibits only early signs for the purpose of decreasing the risk of developing a symptom or pathological sign of the disease, disorder or condition. Thus, the methods disclosed herein include prophylactic methods of treatment. As used herein, “preventing”, “prevent” or “prevention” refers to a course of action initiated prior to infection by, or exposure to, an influenza virus or molecular components thereof and / or before the onset of a symptom or pathological sign of the disease, disorder or condition, so as to prevent infection and / or reduce the symptom or pathological sign. It is to be understood that such preventing need not be absolute to be beneficial to a subject. The immunogenic compositions and / or vaccines of the present disclosure may be used to treat both children and adults. Influenza vaccines are currently recommended for use in paediatric and adult immunisation, from the age of 6 months. Thus, a human subject may be less than 1 year old, 1-5 years old, 5-15 years old, 15-55 years old, or at least 55 years old. Preferred subjects for receiving the vaccines are the elderly (e.g., ^50 years old, ^60 years old, and preferably ^65 years), the young (e.g., ^5 years old), hospitalised subjects, healthcare workers, armed service and military personnel, pregnant women, the chronically ill, immunodeficient subjects, subjects who have taken an antiviral compound in the 7 days prior to receiving the vaccine, people with egg allergies and people travelling abroad. The vaccines are not suitable solely for these groups, however, and may be used more generally in a population. For pandemic strains, administration to all age groups is preferred. Treatment can be by a single dose schedule or a multiple dose schedule. Multiple doses may be used in a primary immunisation schedule and / or in a booster immunisation schedule. In a multiple dose schedule the various doses may be given by the same or different routes (e.g., a parenteral prime and mucosal boost, a mucosal prime and parenteral boost). Administration of more than one dose (typically two doses) is particularly useful in immunologically naïve patients (e.g., for subjects who have never received an influenza vaccine before), or for vaccinating against a new HA subtype (e.g., in a pandemic outbreak). Multiple doses will typically be administered at least 1 week apart (e.g., about 2 weeks apart, about 3 weeks apart, about 4 weeks apart, about 6 weeks apart, about 8 weeks apart, about 10 weeks apart, about 12 weeks apart, about 16 weeks apart, etc.). The immunogenic compositions and / or vaccines of the present disclosure may be used to treat a subject that has been previously infected with an influenza virus. Alternatively, the immunogenic compositions and / or vaccines of the present disclosure may be used to treat a subject that has not been previously infected with an influenza virus (e.g., an immunologically naïve subject). Thus, the methods disclosed herein may include a step of identifying and / or selecting a subject suitable for treatment, based on the identification and / or selection of a subject as having previously been infected with an influenza virus. The invention is further disclosed in the following numbered paragraphs: 1. An immunogenic composition comprising a first haemagglutinin (HA) from a first influenza A virus H3 subtype strain and a second HA from a second influenza A virus H3 subtype strain, wherein the second HA is antigenically distinct from the first HA, and wherein the immunogenic composition is capable of inducing a protective antibody response against other influenza A virus H3 subtype strains. 2. A method of preparing an immunogenic composition, the method comprising selecting a first haemagglutinin (HA) from a first influenza A virus H3 subtype strain and selecting a second HA from a second influenza A virus H3 subtype strain, wherein the second HA is antigenically distinct from the first HA, and wherein the immunogenic composition is capable of inducing a protective antibody response against other influenza A virus H3 subtype strains. 3. The immunogenic composition of paragraph 1 or the method of paragraph 2, wherein the second HA is determined as being antigenically distinct from the first HA as measured using a haemagglutination inhibition (HAI) assay. 4. The immunogenic composition or the method of paragraph 3, wherein the second HA is four or more HAI units apart from the first HA. 5. The immunogenic composition of any one of paragraphs 1, 3 and 4 or the method of any one of paragraphs 2 to 4, wherein the immunogenic composition comprises less than 30 μg of the first HA and less than 30 μg of the second HA. 6. The immunogenic composition of any one of paragraphs 1 and 3 to 5 or the method of any one of paragraphs 2 to 5, wherein the immunogenic composition comprises about 15 μg of the first HA and about 15 μg of the second HA. 7. The immunogenic composition of any one of paragraphs 1 and 3 to 5 or the method of any one of paragraphs 2 to 5, wherein the immunogenic composition comprises about 7.5 μg of the first HA and about 7.5 μg of the second HA. 8. The immunogenic composition of any one of paragraphs 1 and 3 to 7 or the method of any one of paragraphs 2 to 7, wherein the immunogenic composition is capable of inducing a protective antibody response against influenza A virus H3 subtype strains in different sub- clades or clades. . The immunogenic composition of any one of paragraphs 1 and 3 to 8 or the method of any one of paragraphs 2 to 8, wherein the immunogenic composition is capable of inducing a protective antibody response against other influenza A virus H3 subtype strains that emerge after an initial date of emergence of the first influenza A virus H3 subtype strain and / or the second influenza A virus H3 subtype strain. 10. The immunogenic composition of any one of paragraphs 1 and 3 to 9 or the method of any one of paragraphs 2 to 9, wherein the first HA and the second HA are selected from subclade 3C.2a. 11. The immunogenic composition of any one of paragraphs 1 and 3 to 9 or the method of any one of paragraphs 2 to 9, wherein the first HA is selected from subclade 3C.3a and the second HA is selected from subclade 3C.2a, or the first HA is selected from subclade 3C.2a and the second HA is selected from subclade 3C.3a. 12. The immunogenic composition of any one of paragraphs 1 and 3 to 11 or the method of any one of paragraphs 2 to 11, wherein the first and / or the second influenza A virus H3 subtype strain is a H3N2 strain. 13. The immunogenic composition or the method of paragraph 12, wherein the first HA is selected from an A / Kansas / 14 / 2017 / H3N2 strain and the second HA is selected from an A / South Australia / 34 / 2019 / H3N2 strain. 14. The immunogenic composition of any one of paragraphs 1 and 3 to 13 or the method of any one of paragraphs 2 to 13, wherein the first influenza A virus H3 subtype strain is recommended for inclusion in an immunogenic composition by a public health authority. 15. The immunogenic composition of any one of paragraphs 1 and 3 to 14 or the method of any one of paragraphs 2 to 14, wherein the immunogenic composition comprises a further HA selected from an influenza A virus strain of a H1, H2, H3, H5, H7, H9, or H10 subtype. 16. The immunogenic composition or method of paragraph 15, wherein the further HA is selected from a H1N1 strain. 17. The immunogenic composition of any one of paragraphs 1 and 3 to 16 or the method of any one of paragraphs 2 to 16, wherein the immunogenic composition comprises a further HA selected from an influenza B virus. 18. The immunogenic composition or method of paragraph 17, wherein the further HA is selected from an influenza B virus which is a B / Victoria strain. 19. The immunogenic composition of any one of paragraphs 1 and 3 to 18 or the method of any one of paragraphs 2 to 18, wherein the immunogenic composition comprises a HA selected from a H1N1 strain and a HA selected from a B / Victoria strain. 20. An immunogenic composition comprising: a first haemagglutinin (HA) from a first influenza A virus H3 subtype strain and a second HA from a second influenza A virus H3 subtype strain, wherein the second HA is antigenically distinct from the first HA; and a further HA selected from an influenza A virus strain of a H1, H2, H3, H5, H7, H9, or H10 subtype or a further HA selected from an influenza B virus, wherein the first HA and the second HA are each provided at a dose that is less than the dose of the further HA. 21. The immunogenic composition of paragraph 20, wherein the further HA is provided at a standard dose. 22. The immunogenic composition of paragraph 20 or paragraph 21, wherein the first HA and the second HA are each provided at half the dose of the further HA. 23. The immunogenic composition of any one of paragraphs 20 to 22, wherein the further HA is selected from a H1N1 strain. 24. The immunogenic composition of any one of paragraphs 20 to 23, wherein the further HA is selected from an influenza B virus. 25. The immunogenic composition of paragraph 24, wherein the influenza B virus is a B / Victoria strain. 26. The immunogenic composition of any one of paragraphs 20 to 25, which is a trivalent or a quadrivalent composition. 27. The immunogenic composition of any one of paragraphs 20 to 26, which is capable of inducing a protective antibody response against other influenza A virus H3 subtype strains. 28. The immunogenic composition of any one of paragraphs 20 to 27, modified by the features of any one or more of paragraphs 3 to 14. 29. A vaccine comprising the immunogenic composition of any one of paragraphs 1 and 3 to 28 or an immunogenic composition prepared by the method of any one of paragraphs 2 to 19, and a pharmaceutically acceptable carrier, diluent or excipient. 30. The immunogenic composition of any one of paragraphs 1 and 3 to 28, or the vaccine of paragraph 29, further comprising an adjuvant. 31. The immunogenic composition or vaccine of paragraph 30, wherein the adjuvant is MF59. 32. A method of treating and / or preventing an influenza-associated disease, disorder or condition in a subject, the method comprising administering a therapeutically effective amount of the immunogenic composition of any one of paragraphs 1, 3-28 and 30-31, an immunogenic composition prepared by the method of any one of paragraphs 2 to 19, or the vaccine of any one of paragraphs 29 to 31, to the subject. 33. The method of paragraph 32, wherein the subject has previously been infected with an influenza virus. 34. The method of paragraph 32 or paragraph 33, wherein the immunogenic composition is administered to the subject two or more times at selected time intervals. 35. Use of the immunogenic composition of any one of paragraphs 1, 3-28 and 30-31, an immunogenic composition prepared by the method of any one of paragraphs 2 to 19, or the vaccine of any one of paragraphs 29 to 31, in the manufacture of a medicament for treating and / or preventing an influenza-associated disease, disorder or condition in a subject. 36. The immunogenic composition of any one of paragraphs 1, 3-28 and 30-31, an immunogenic composition prepared by the method of any one of paragraphs 2 to 19, or the vaccine of any one of paragraphs 29 to 31, for use in treating and / or preventing an influenza- associated disease, disorder or condition in a subject. 37. A container comprising a sterile liquid formulation of, or a lyophilised composition comprising, the immunogenic composition of any one of paragraphs 1, 3-28 and 30-31, an immunogenic composition prepared by the method of any one of paragraphs 2 to 19, or the vaccine of any one of paragraphs 29 to 31. 38. The container of paragraph 37, which is a syringe, vial or ampoule. In order that preferred embodiments of the present disclosure may be fully understood and put into practical effect, reference is made to the following non-limiting examples. Examples Example 1. General methodology for performing HAI assays on serum from ferrets vaccinated with selected influenza viruses. Outbred naïve ferrets were vaccinated with selected influenza viruses and two weeks post vaccination whole blood was collected in a tube containing a gel plug and allowed to clot undisturbed at room temperature. The tube was centrifuged at 2000 g for 10 minutes to separate serum from blood. The ferret serum was then aliquoted from the tube and placed in a clean tube. One volume of ferret serum was incubated overnight in a 37°C water bath in the presence of 4 volumes of receptor-destroying enzyme (RDE) and then resuspended in 5 volumes of 1.6% (w / v) sodium citrate and heated for 30 min in a 56°C water bath. In a U-bottom 96-well plate, 25 μL of RDE-treated serum was 2-fold serially diluted in 25 μL of PBS. Virus stocks were titred by hemagglutination (HA) assay. 25ul of virus was serially diluted 2- fold in a U-bottom 96-well plate in 25ul PBS.25 ul of 1 % guinea pig RBC were added to each well and the plate gently tapped to ensure uniform mixing. Plates were incubated at room temperature for 1 h, prior to reading. The hemagglutinating units (HAU) were determined, then the virus diluted in PBS to 4 HAU. This was confirmed by a HA assay. This assay was performed in triplicate. Four HAU of a H3N2 influenza A virus in 25ul of PBS was added to each well and the plates gently agitated. The H3N2 influenza A viruses tested were A / Victoria / 182 / 1982, A / Kansas / 14 / 2017 IVR-195, A / South Australia / 34 / 2019 IVR-197, A / Hong Kong / 2671 / 2019 IVR-208, A / Perth / 20 / 2020 IVR-220, A / Tasmania / 503 / 2020 IVR-221, A / Cambodia / e08263601 / 2020 IVR-224 and A / Darwin / 6 / 2021 IVR-227. The virus stocks were either monovalent pooled harvest or live virus from Seqirus Inc. virus stocks. Plates were incubated for 30 min at room temperature and then 25 μL of 1% guinea pig RBCs was added. Plates were then incubated at room temperature for 1 hr. The haemagglutination inhibition (HAI) titres were determined by visual inspection of the last well in which haemagglutination of RBC did not occur, and reported as the reciprocal of the dilution. Example 2. Vaccination with two influenza A subtype H3 HA antigens In this Example the inventors investigated the effect of vaccination with two influenza A(H3) antigens (exemplified here as H3N2 antigens) on the induction of antibodies to each of the vaccine strains as compared to the induction of antibodies when vaccinating with a single influenza A(H3) antigen (again, exemplified herein as a H3N2 antigen) alone. Methods and Results Assessing the immune response to vaccine antigens in naïve ferrets receiving vaccine To assess the benefit of immunisation with two antigenically distinct influenza A(H3N2) viruses, naïve ferrets were immunised with monovalent pooled harvest (MPH) from a clade 3C.3a virus, A / Kansas / 14 / 2017 IVR-195 and / or MPH from a clade 3C.2a1b virus (3C.2a1b.2 subclade), A / South Australia / 34 / 2019 IVR-197. Naïve ferrets were intramuscularly immunised in a three dose (prime-boost-boost) vaccination regimen with either the 3C.3a or 3C.2a1b virus or a combination of the two (Figure 1A, Table 1). All ferrets received a total of 30 μg HA / dose, thus either 30 μg HA of a single antigen, or 15 μg HA each antigen to combine to a total dose of 30 μg HA. Table 1. Vaccination regimen for naïve ferrets receiving three doses (prime-boost-boost). Naïve ferrets were also vaccinated in a two dose (prime-boost) vaccination regimen with either MF59-adjuvanted 3C.3a (15 μg HA / dose) or MF59-adjuvanted 3C.2a1b (15 μg HA / dose) antigen (Figure 1B, Table 2). In this two dose regimen, the prime was administered at Week 0 and boost at Week 2. Table 2. Vaccination regimen for naïve ferrets receiving an adjuvanted prime-boost Assessing the immune response to vaccine antigens in naïve ferrets receiving unadjuvanted or adjuvanted vaccine Following the immunisation of the three doses (prime-boost-boost) in naïve ferrets, extremely low levels of antibodies were detected by Haemagglutination Inhibition (HAI) assay. HAI antibodies to A / Kansas / 14 / 2017 IVR-195 were not detected in animals that received three doses of this antigen at 30 μg HA / dose (Kan>Kan>Kan) (Figure 2). However, HAI antibodies were detected at extremely low levels (HAI titre of 20) in ferrets dosed three times with a combination of antigens, containing only 15 μg HA A / Kansas / 14 / 2017 IVR-195 (SA+Kan > SA+Kan > SA+Kan). HAI antibodies to A / South Australia / 34 / 2019 IVR-197 were only detected in animals that received three doses of this antigen at 30 μg / dose (SA > SA > SA), and not when it was dosed in a combination of antigens, containing only 15 μg HA A / South Australia / 34 / 2019 IVR- 197 (SA+Kan > SA+Kan > SA+Kan). HAI antibodies were not detected against other viruses tested (ancestral A / Victoria / 182 / 1982, recent A / Hong Kong / 2671 / 2019 IVR-208, A / Perth / 20 / 2020 IVR-220, A / Tasmania / 503 / 2020 IVR-221, A / Cambodia / e08263601 / 2020 IVR- 224 and A / Darwin / 6 / 2021 IVR-227). The HAI titres are also presented in a heat map in Figure . Following the adjuvanted two dose (prime-boost) immunisation of naïve ferrets, seroconversion towards the vaccine antigens were detected by HAI assay (Figure 3). HAI antibodies to A / Kansas / 14 / 2017 IVR-195 were observed at 2 weeks after the first dose (post prime) and were further increased after ferrets received the second vaccine dose (4 weeks post prime, 2 weeks post boost) at 15 μg / dose (Kan>Kan) (HAI titre 40-80 after first dose, 160-640 after second dose, Figure 3). The same was observed for A / South Australia / 34 / 2019 IVR-197, where the HAI antibody titre in ferrets increased from 80 after the first dose, to 640 after two doses (Figure 3). HAI antibodies towards a panel of viruses from other circulating H3N2 clades were detected against A / Hong Kong / 2671 / 2019 IVR-208 (3C.2a1b.1b subclade), A / Tasmania / 503 / 2020 IVR- 221 and A / Cambodia / e08263601 / 2020 IVR-224 (3C.2a1b.2a subclade) in ferrets vaccinated with A / South Australia / 34 / 2019 IVR-197 at 2 weeks after the second dose (4 weeks post prime, 2 weeks post boost). No HAI antibodies were detected against the ancestral A / Victoria / 182 / 1982 strain, A / Perth / 20 / 2020 IVR-220 (3C.2a1b.1c subclade) or A / Darwin / 6 / 2021 IVR-227 (3C.2a1b.2a.2a) for either group. The HAI titres are also presented in a heat map in Figure 5. Assessing the immune response to vaccine antigens in ferrets with pre-existing immunity receiving vaccine Anaesthetised ferrets were intranasally infected with 1 mL of PBS containing 100xTCID50 / mL of the ancestral A(H3N2) strain A / Victoria / 182 / 1982. The ferrets were allowed to recover from infection and were vaccinated with a two dose (prime-boost) vaccination regimen. Infection with A / Victoria / 182 / 1982 induces high levels of antibodies to the infection strain after 28 days (Week 4), but minimal antibodies to other H3N2 strains included in this study (Figure 4, timepoint 0 in all graphs). Thus, infection with A / Victoria / 182 / 1982 provides activation of the immune response, but not antigen specificity that cross-reacts with the vaccines utilised in the combined dose regimen. Ferrets were vaccinated with either 3C.3a (30 μg HA / dose) or 3C.2a1b (30 μg HA / dose) antigen or a combination of the two at reduced doses (15 μg HA each antigen, for a total of 30 μg HA / dose) (Figure 1C, Table 3). Table 3. Vaccination regimen for ferrets intranasally infected with an ancestral A(H3N2) influenza virus prior to receiving a prime-boost-boost Following the three dose (prime-boost-boost), non-adjuvanted immunisation regimen in pre- infected ferrets, seroconversion towards the vaccine antigens were detected by HAI assay (Figure 4). HAI antibodies to A / Kansas / 14 / 2017 IVR-195 were observed at 2 weeks after the first dose (post prime) and remained consistent after the second and third dose in animals that received 30 ug HA / dose (Kan>Kan>Kan) (Figure 4B). For ferrets that received A / South Australia / 34 / 2019 IVR-197, titres were high after the first and second doses (Figure 4E). Ferrets that received 15 μg of both A / Kansas / 14 / 2017 IVR-195 and A / South Australia / 34 / 2019 IVR-197 (SA+Kan > SA+Kan > SA+Kan) had HAI titres at 2 weeks after the first dose towards both A / Kansas / 14 / 2017 and A / South Australia / 34 / 2019. These titres remained relatively stable after the second and third vaccination doses (2 weeks post each boost; Figure 4B and E). HAI antibodies towards the pre-infection challenge strain (A / Victoria / 182 / 1982) were increased after challenge and were relatively stable over all bleeds in animals that received the combination vaccine. There was a gradual decline in titres in animals that received a single antigen (Figure 4A). HAI antibodies towards a panel of other circulating H3N2 clades were also observed against A / Hong Kong / 2671 / 2019 IVR-208, A / Perth / 20 / 2020 IVR-220, A / Tasmania / 503 / 2020 IVR-221, A / Cambodia / e08263601 / 2020 IVR-224 and A / Darwin / 6 / 2021 IVR-227. Ferrets receiving 15 μg of both A / Kansas / 14 / 2017 IVR-195 and A / South Australia / 34 / 2019 IVR-197 (SA+Kan > SA+Kan > SA+Kan) had the broadest antibody response with several HAI titres augmented when compared to ferrets receiving a single antigen alone (for example to A / Perth / 20 / 2020 IVR-220, A / Cambodia / e08263601 / 2020 and A / Tasmania / 503 / 2020 IVR-221). The HAI titres are also presented in a heat map in Figure 5. Summary The present Example demonstrates that: x Vaccination with A(H3N2) antigens alone in naïve ferrets did not demonstrate significant immunogenicity of the antigen or result in a significant antibody response, though responses were improved by the addition of an adjuvant. x Using ferrets previously infected with an ancestral A(H3N2) influenza strain increased the immunogenicity of the antigen and antibody response. x Immunisation with a combination of two antigenically distinct A(H3N2) antigens at half the dose resulted in antibody responses to both components to similar levels as receiving a single antigen at double the dose, with the additional benefit of inducing antibodies to non-vaccine influenza strains, including in particular, strains that only emerged later than the vaccine antigen strains. The present example provides the first compelling evidence of particular advantages of using two antigenically distinct H3 HA antigens together in a vaccine. The experimental results disclosed herein demonstrate that the inclusion of two H3 HA antigens from different strains, at an amount less than a comparative, ‘standard’ dose that might be used to administer a single strain antigen, achieves a greater immunogenic response to the two vaccine strains and further, other, unrelated and later-emerging strains. These data therefore provide a powerful insight into new vaccine designs based on the inclusion of antigenically distinct H3 antigens in multivalent compositions, such as trivalent or quadrivalent compositions.

Claims

Claims:

1. An immunogenic composition comprising a first haemagglutinin (HA) from a first influenza A virus H3 subtype strain and a second HA from a second influenza A virus H3 subtype strain, wherein the second HA is antigenically distinct from the first HA, and wherein the immunogenic composition is capable of inducing a protective antibody response against other influenza A virus H3 subtype strains.

2. A method of preparing an immunogenic composition, the method comprising selecting a first haemagglutinin (HA) from a first influenza A virus H3 subtype strain and selecting a second HA from a second influenza A virus H3 subtype strain, wherein the second HA is antigenically distinct from the first HA, and wherein the immunogenic composition is capable of inducing a protective antibody response against other influenza A virus H3 subtype strains.

3. The immunogenic composition of claim 1, wherein the second HA is determined as being antigenically distinct from the first HA as measured using a haemagglutination inhibition (HAI) assay.

4. The immunogenic composition of claim 3, wherein the second HA is four or more HAI units apart from the first HA.

5. The immunogenic composition of claim 1, wherein the immunogenic composition comprises less than 30 μg of the first HA and less than 30 μg of the second HA.

6. The immunogenic composition of claim 1, wherein the immunogenic composition comprises about 15 μg of the first HA and about 15 μg of the second HA.

7. The immunogenic composition of claim 1, wherein the immunogenic composition comprises about 7.5 μg of the first HA and about 7.5 μg of the second HA.

8. The immunogenic composition of claim 1, wherein the immunogenic composition is capable of inducing a protective antibody response against influenza A virus H3 subtype strains in different sub-clades or clades.

9. The immunogenic composition of claim 1, wherein the immunogenic composition is capable of inducing a protective antibody response against other influenza A virus H3 subtype strains that emerge after an initial date of emergence of the first influenza A virus H3 subtype strain and / or the second influenza A virus H3 subtype strain.

10. The immunogenic composition of claim 1, wherein the first HA and the second HA are selected from subclade 3C.2a.

11. The immunogenic composition of claim 1, wherein the first HA is selected from subclade 3C.3a and the second HA is selected from subclade 3C.2a, or the first HA is selected from subclade 3C.2a and the second HA is selected from subclade 3C.3a.

12. The immunogenic composition of claim 1, wherein the first and / or the second influenza A virus H3 subtype strain is a H3N2 strain.

13. The immunogenic composition of claim 12, wherein the first HA is selected from an A / Kansas / 14 / 2017 / H3N2 strain and the second HA is selected from an A / South Australia / 34 / 2019 / H3N2 strain.

14. The immunogenic composition of claim 1, wherein the first influenza A virus H3 subtype strain is recommended for inclusion in an immunogenic composition by a public health authority.

15. The immunogenic composition of claim 1, wherein the immunogenic composition comprises a further HA selected from an influenza A virus strain of a H1, H2, H3, H5, H7, H9, or H10 subtype.

16. The immunogenic composition of claim 15, wherein the further HA is selected from a H1N1 strain.

17. The immunogenic composition of claim 1, wherein the immunogenic composition comprises a further HA selected from an influenza B virus.

18. The immunogenic composition of claim 17, wherein the further HA is selected from an influenza B virus which is a B / Victoria strain.

19. The immunogenic composition of claim 1, wherein the immunogenic composition comprises a HA selected from a H1N1 strain and a HA selected from a B / Victoria strain.

20. An immunogenic composition comprising: a first haemagglutinin (HA) from a first influenza A virus H3 subtype strain and a second HA from a second influenza A virus H3 subtype strain, wherein the second HA is antigenically distinct from the first HA; and a further HA selected from an influenza A virus strain of a H1, H2, H3, H5, H7, H9, or H10 subtype or a further HA selected from an influenza B virus,wherein the first HA and the second HA are each provided at a dose that is less than the dose of the further HA.

21. The immunogenic composition of claim 20, wherein the further HA is provided at a standard dose.

22. The immunogenic composition of claim 20, wherein the first HA and the second HA are each provided at half the dose of the further HA.

23. The immunogenic composition of claim 20, wherein the further HA is selected from a H1N1 strain.

24. The immunogenic composition of claim 20, wherein the further HA is selected from an influenza B virus.

25. The immunogenic composition of claim 24, wherein the influenza B virus is a B / Victoria strain.

26. The immunogenic composition of claim 20, which is a trivalent or a quadrivalent composition.

27. The immunogenic composition of claim 20, which is capable of inducing a protective antibody response against other influenza A virus H3 subtype strains.

28. The immunogenic composition of claim 20, modified by the features of claim 3.

29. A vaccine comprising the immunogenic composition of claim 1, and a pharmaceutically acceptable carrier, diluent or excipient.

30. The vaccine of claim 29, further comprising an adjuvant.

31. The vaccine of claim 30, wherein the adjuvant is MF59.

32. A method of treating and / or preventing an influenza-associated disease, disorder or condition in a subject, the method comprising administering a therapeutically effective amount of the immunogenic composition of claim 1 or an immunogenic composition prepared by the method of claim 2, to the subject.

33. The method of claim 32, wherein the subject has previously been infected with an influenza virus.

34. The method of claim 32, wherein the immunogenic composition is administered to the subject two or more times at selected time intervals.

35. Use of the immunogenic composition of claim 1 or an immunogenic composition prepared by the method of claim 2, in the manufacture of a medicament for treating and / or preventing an influenza-associated disease, disorder or condition in a subject.

36. The immunogenic composition of claim 1 or an immunogenic composition prepared by the method of claim 2, for use in treating and / or preventing an influenza-associated disease, disorder or condition in a subject.

37. A container comprising a sterile liquid formulation of, or a lyophilised composition comprising, the immunogenic composition of claim 1 or an immunogenic composition prepared by the method of claim 2.

38. The container of claim 37, which is a syringe, vial or ampoule.

Images