ANTIBODIES AND TREATMENT METHODS FOR INFLUENZA A INFECTION

Abstract

The present invention provides antibodies that neutralize influenza A virus infection. The present invention also provides nucleic acids that encode and immortalize cultured B cells and plasma cells that produce these antibodies. In addition, the present invention provides for the use of the antibodies of the present invention in the prevention and treatment of influenza A infection.

Description

ANTIBODIES AND TREATMENT METHODS FOR INFLUENZA A INFECTION Invention Engineering Field The present invention relates to antibodies that potentially reduce influenza A infection and the uses of such antibodies. Specifically, the invention relates to the prophylaxis and treatment of influenza A infection. Background of the Invention Influenza is an infectious disease, which spreads worldwide in annual outbreaks resulting in approximately three to five million cases of severe illness per year and approximately 290,000 to 650,000 respiratory deaths (WHO, Influenza (Seasonal) Fact sheet, 6 November 2018). The most common symptoms include: sudden onset of fever, cough (usually dry), headache, muscle and joint pain, severe malaise (feeling unwell), sore throat, and runny nose. The incubation period varies between one and four days, although symptoms usually begin about two days after exposure to the virus. Complications of influenza can include pneumonia, sinus infections, worsening of pre-existing health problems such as asthma or heart failure, sepsis, or exacerbation of underlying chronic diseases. Influenza is caused by influenza viruses, an antigenically and genetically diverse group of viruses in the family Orthomyxoviridae that contain a single-stranded, negative-sense RNA genome. Of the four types of influenza viruses (A, B, C, and D), three types (A, B, and C) infect humans. Influenza type A viruses are the most virulent human pathogens and cause the most severe disease. Influenza A viruses can be categorized based on the different subtypes of the main surface proteins present: Hemagglutinin (HA) and Neuraminidase (NA). There are at least 18 subtypes of influenza A defined by their hemagglutinin (HA) proteins. HA can be classified into two groups. Group 1 contains subtypes H1, H2, H5, H6, H8, H9, H11, H12, H13, H16, and H17, and group 2 includes H subtypes 3, H4, H7, H10, H14, and H15. While all subtypes are found in birds, most subtypes H1, H2 and H3 cause disease in humans.The H5, H7, and H9 subtypes cause sporadic severe infections in humans and can trigger new pandemics. Influenza A viruses continually evolve, producing new variants, a phenomenon called antigenic drift. As a result, antibodies produced in response to past viruses are less or no longer protective against newly emerging H1 and H3 viruses. Consequently, new vaccines must be produced annually to combat the predicted emergence of H1 and H3 viruses, a process that is very expensive and not always efficient. The same applies to the production of H5 influenza vaccines. HA is the major surface protein of influenza A virus, which is the primary target of neutralizing antibodies induced by infection or vaccination. HA is responsible for binding the virus to cells with sialic acid in the membrane, such as cells in the upper respiratory tract or erythrocytes. In addition, HA mediates the fusion of the viral envelope with the endosomal membrane, after the pH is lowered. HA is a homotrimeric integral membrane glycoprotein. The HA trimer consists of three identical monomers, each made of a single intact HA0 polypeptide chain with HA1 and HA2 regions connected by two disulfide bridges. Each HA2 region adopts an alpha-helical coiled coil structure and mainly forms the stem or stalk region of HA, while the HA1 region HA1 is a small globular domain containing a mixture of α / β structures (the HA head region). The globular HA head region mediates binding to sialic acid receptors, while the HA stalk mediates subsequent fusion between the virus and the cellular membrane, triggered in endosomes by low pH. While the immunodominant globular HA head domain has high plasticity with distinct antigenic sites undergoing constant antigenic shifts, the HA stalk region is relatively conserved among subtypes. Current influenza vaccines predominantly induce immune responses against the immunodominant and variable HA head regions, which evolve faster than the HA stalk region (Kirkpatrick E, Qiu X, Wilson PC, Bahl J, Krammer F. The influenza virus hemagglutinin head evolves faster than the stalk domain. Sci Rep. 2018 Jul 11;8(1):10432). Therefore, a given influenza vaccine typically provides protection for no more than a few years, and annual redevelopment of influenza vaccines is necessary. Brief Description of the Invention To address this issue, a new class of influenza neutralizing antibodies targeting conserved sites in the HA stem has recently been developed for influenza virus therapy. These antibodies targeting the HA stem region typically neutralize more broadly than antibodies targeting the HA head region. An overview of broadly neutralizing influenza A antibodies is provided in Corti D. and Lanzavecchia A., Broadly neutralizing antiviral antibodies. Annu. Rev. Immunol. 2013; 31:705-742. Okuno et al. mice immunized with influenza A / Okuda / 57 (H2N2) virus and isolated a monoclonal antibody (C179) that binds to a conserved conformational epitope in HA2 and neutralizes influenza A viruses of Group 1 subtypes H2, H1 and H5 in vitro and in vivo in animal models (Okuno et al.,1993; Smirnov et al., 1999; Smirnov et al., 2000).Contoh lebih lanjut dari antibodi penargetan daerah HA-batang termasuk: CR6261 (Throsby M, van den Brink E, Jongeneelen M, Poon LLM, Alard P, Cornelissen L, et al. (2008) Heterosubtypic Neutralizing Monoclonal Antibodies Cross-Protective against H5N1 and H1N1 Recovered from Human IgM+ Memory B Cells. PLoS ONE 3(12): e3942. https: / / doi.org / 10.1371 / journal.pone.0003942; Friesen RHE, Koudstaal W, Koldijk MH, Weverling GJ, Brakenhoff JPJ, Lenting PJ, et al. (2010) New Class of Monoclonal Antibodies against Severe Influenza: Prophylactic and Therapeutic Efficacy in Ferrets. PLoS ONE 5(2): e9106. https: / / doi.org / 10.1371 / journal.pone.0009106), F10 (Sui J, Hwang WC, Perez S, Wei G, Aird D, Chen LM, Santelli E, Stec B, Cadwell G, Ali M, Wan H, Murakami A, Yammanuru A, Han T, Cox NJ, Bankston LA, Donis RO, Liddington RC, Marasco WA (March 2009). Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nature Structural & Molecular Biology.16(3): 265-7 doi:10.1038 / nsmb.1566), CR8020 (Ekiert DC, Friesen RHE, Bhabha G, Kwaks T, Jongeneelen M, et al. 2011. A highly conserved neutralizing epitope on group 2 influenza A viruses. Science 333(6044):843-50), FI6 (Corti D, Voss). J, Gamblin SJ, Codoni G, Macagno A, et al R, et al.2012. Highly conserved protective epitopes on influenza B viruses Science 337(6100):1343-48. Now, antibodies that do not react with each child HA of both group 1 and 2 subtypes are very rare and usually do not show complete coverage of all subtypes. Recently, the antibody MEDI8852 was described, which potently neutralizes influenza A viruses of groups 1 and 2 with unprecedented breadth, capable of neutralizing a diverse panel of representative viruses spanning >80 years of antigenic evolution (Kallewaard NL, Corti D, Collins PJ, et al. Structure and Function Analysis of an Antibody Recognizing All Influenza A Subtypes. Cell. 2016;166(3):596-608; Paules, CI et al. The Hemagglutinin A Stem Antibody MEDI8852 Prevents and Controls Disease and Limits Transmission of Pandemic Influenza Viruses. J Infect Dis 216, 356-365, https: / / doi.org / 10.1093 / infdis / jix292 (2017)). MEDI8852 was shown to bind a highly conserved epitope that is very different from structurally characterized stem-reactive neutralizing antibodies (Kallewaard NL, Corti D, Collins PJ, et al.Structure and Function Analysis of an Antibody Recognizing All Influenza A Subtypes. Cell. 2016; 166(3):596608). In view of the above, it is an object of the present invention to provide a novel antibody, which broadly and efficiently neutralizes influenza A virus, even when administered at very low doses. This objective is achieved through the subject matter set out below and in the attached claims. Although the present invention is described in detail below, it should be understood that the present invention is not limited to the particular methodology, protocol, and reagents described herein as they may vary. It should also be understood that the terms used herein are not intended to limit the scope of the present invention, which shall be limited only by the appended claims. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as generally understood by those skilled in the art. In the following, the elements of the present invention will be described. These elements are listed with specific embodiments; however, it should be understood that they may be combined in any manner and in any quantity to create additional embodiments. The various examples and embodiments described should not be construed to limit the present invention to only the explicitly described embodiments. This description should be understood to support and include embodiments that combine the explicitly described embodiments with any number of disclosed elements. Furthermore, any permutations and combinations of all the elements described in this application should be deemed to be disclosed by the description of this application unless the context indicates otherwise. Throughout this specification and the claims that follow, unless the context otherwise requires, the term comprises, and variations such as comprise and comprising, will be understood to imply the inclusion of the stated members, integers, or steps but not the exclusion of any other unstated members, integers, or steps. The term comprises only is a specific embodiment of the term comprises, in which any other unstated members, integers, or steps are excluded. In the context of the present invention, the term comprises includes the term comprises only. The term comprises thus includes including as well as comprising e.g., a composition comprising X may consist exclusively of X or may include something additional e.g., X + Y. The terms a (a) and an (an) and the (the) and similar references used in the context of describing the invention (especially in the context of the claims) shall be construed to include both the singular and plural forms, unless otherwise stated herein. or clearly contradicted by the context. The reading of a range of values ​​herein is intended only as a shorthand method for referring individually to each separate value falling within that range. Unless otherwise stated herein, each individual value is incorporated into the specification as if it were individually disclosed herein. No language in the specification shall be construed as indicating non-claim elements essential to the practice of the invention. The word substantially does not exclude completely for example, a composition substantially free from Y may be completely free from Y. If necessary, the word substantially may be omitted from the definition of an invention. The term around in relation to a numerical value x means x ± 10%, for example, x ± 5%, or x ± 7%, or x ± 10%, or x ± 12%, or x ± 15%, or x ± 20%. The term disease as used herein is intended to be generally synonymous with, and used interchangeably with, the terms disorder and condition (as in medical condition), all of which reflect an abnormal condition of the human or animal body or any part thereof that interferes with normal functioning, is usually manifested by distinct signs and symptoms, and causes the human or animal to experience a reduction in the duration or quality of life. As used herein, references to treatment of a subject or patient are intended to include prevention, prophylaxis, attenuation, remediation, and therapy. The terms subject and patient are used interchangeably herein to mean all mammals, including humans. Examples of subjects include humans, cattle, dogs, cats, horses, goats, sheep, pigs, and rabbits. In some embodiments, the patient is a human. Doses are often expressed in relation to body weight. Thus, a dose expressed as [g, mg, or other unit] / kg (or g, mg, etc.) usually refers to [g, mg, or other unit] per kg (or g, mg, etc.) of body weight, even if the term body weight is not explicitly mentioned. The term specific binding and similar references do not include non-specific attachment. As used herein, the term antibody includes various forms of antibodies including, without limitation, whole antibodies, antibody fragments, human antibodies, chimeric antibodies, humanized antibodies, recombinant antibodies, and genetically engineered antibodies (variant or mutant antibodies) as long as the characteristic properties according to the invention are retained. In some embodiments, the antibody is a human antibody. In some embodiments, the antibody is a monoclonal antibody. For example, the antibody is a human monoclonal antibody. Human antibodies are well known in the field (van Dijk, MA, and van de Winkel, JG, Curr. Opin. Chem. Biol. 5 (2001) 368-374). Human antibodies can also be produced in transgenic animals (e.g., mice) that are capable, upon immunization, of producing the full or selected repertoire of human antibodies in the absence of endogenous immunoglobulin production. Transfer of human germ-line immunoglobulin gene sequences into such germ-line mutant mice results in the production of human antibodies upon antigen challenge (see, e.g., Jakobovits, A., et al., Proc. Natl. Acad. Sci. USA 90 (1993) 2551-2555; Jakobovits, A., et al., Nature 362 (1993) 255-258; Bruggemann, M., et al., Year Immunol. 7 (1993) 3340). Human antibodies can also be produced in phage display libraries (Hoogenboom, H.R., and Winter, G., J. Mol. Biol. 227 (1992) 381-388; Marks, J.D., et al., J. Mol. Biol. 222 (1991) 581-597). The techniques of Cole et al. and Boerner et al. are also available for the production of human monoclonal antibodies (Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p. 77 (1985); and Boerner, P., et al., J. Immunol. 147 (1991) 86-95). In some embodiments, human monoclonal antibodies are made using enhanced immortalization of EBV-B cells as described in Traggiai E, Becker S, Subbarao K, Kolesnikova L, Uematsu Y, Gismondo MR, Murphy BR, Rappuoli R, Lanzavecchia A. (2004): An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirus. Nat Med. 10(8):871-5. As used herein, the term “variable region” (light chain variable region (Vl), heavy chain variable region (VH)) denotes the respective light and heavy chain pairs directly involved in binding the antibody to the antigen. The antibodies of the present invention may be of any isotype (e.g., IgA, IgG, IgM, i.e., an α, γ, or μ heavy chain). For example, the antibody is of the IgG type. Within the IgG isotype, the antibody may be of the IgG1, IgG2, IgG3, or IgG4 subclasses, for example, IgG1. The antibodies of the present invention may have: a κ or λ light chain. In some embodiments, the antibody is of the IgG1 type and has a κ light chain. Antibodies according to the present invention may be provided in purified form. Typically, the antibodies will be present in a composition substantially free from other polypeptides, for example, where less than 90% (by weight), usually less than 60% and more usually less than 50% of the composition consists of other polypeptides. Antibodies according to the invention may be immunogenic in humans and / or in non-human (or heterologous) hosts such as mice. For example, antibodies may have idiotopes that are immunogenic in non-human hosts, but not in human hosts. Antibodies of the invention for human use include those that cannot be readily isolated from hosts such as mice, goats, rabbits, rats, non-primate mammals, etc. and generally cannot be obtained by humanization or from xeno-mice. As used herein, a “neutralizing antibody” is an antibody that can neutralize, that is, prevent, inhibit, reduce, hinder, or interfere with, the ability of a pathogen to initiate and / or perpetuate infection in a host. The terms neutralizing antibody and neutralizing antibody or neutralizing antibody are used interchangeably herein. These antibodies may be used alone, or in combination, as prophylactic or therapeutic agents in appropriate formulations, in conjunction with active vaccination, as diagnostic tools, or as production tools as described herein. As used herein, the term mutation refers to a change in the nucleic acid sequence and / or amino acid sequence compared to a reference sequence, e.g., the corresponding genome sequence. Mutations, e.g., compared to the genome sequence, can be, for example, somatic mutations (naturally occurring), spontaneous mutations, induced mutations, e.g., induced by enzymes, chemicals, or radiation, or mutations obtained by site-directed mutagenesis (a molecular biology method for making specific and deliberate changes in the nucleic acid sequence and / or amino acid sequence). Thus, the term mutation or mutate should be understood to also include physically making a mutation, e.g., in the nucleic acid sequence or in the amino acid sequence. Mutations include substitutions, deletions, and insertions of one or more nucleotides or amino acids, as well as inversions of several consecutive nucleotides or amino acids.To achieve mutations in amino acid sequences, mutations can be introduced into the nucleotide sequence that codes for that amino acid sequence to express a mutated (recombinant) polypeptide. Mutations can be achieved for example by changing, for example, by site-directed mutagenesis, the codon of a nucleic acid molecule that codes for one amino acid to produce a codon that codes for a different amino acid, or by synthesizing a sequence variant, for example by knowing the nucleotide sequence of a nucleic acid molecule that codes for a polypeptide and by designing the synthesis of a nucleic acid molecule that comprises the nucleotide sequence that codes for the variant polypeptide without the need to mutate one or more nucleotides of the nucleic acid molecule. Several documents are referenced throughout the text of this specification. Each document referred to herein (including all patents, patent applications, scientific publications, manufacturer's specifications, instructions, etc.), whether supra or infra, is hereby incorporated by reference in its entirety. Nothing herein shall be construed as an admission that the invention is not entitled to preemption by virtue of such prior art. It should be understood that the present invention is not limited to the particular methodologies, protocols, and reagents described herein, as these may vary. It should also be understood that the terms used herein are for the purpose of describing particular embodiments only, and are not intended to limit the scope of the present invention, which shall be limited only by the appended claims. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as generally understood by those skilled in the art. Antibody The present invention is based, among other things, on the identification of an antibody that has the potential to reduce influenza A infection even when administered at very low doses. Furthermore, the antibody of the present invention exhibits an increased half-life. Without being bound by any theory, the present inventors assume that the increased potency of the antibody of the present invention is independent of the increased half-life. For example, compared to a comparative antibody, the antibody of the present invention exhibits increased potency even though the antibody concentration in plasma is similar. Furthermore, the antibody of the present invention surprisingly exhibits decreased immunogenicity compared to the parent antibody without the M428L and N434S mutations in the heavy chain constant region. In a first aspect, the present invention provides an antibody (isolated) comprising the heavy chain sequences CDR1, CDR2, and CDR3 as set forth in SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3; the light chain sequences CDR1, CDR2, and CDR3 as set forth in SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6; and the mutations M428L and N434S in the constant region of the heavy chain. In general, an antibody according to the present invention typically comprises (at least) three complementarity determining regions (CDRs) on a heavy chain and (at least) three CDRs on a light chain. In general, the complementarity determining regions (CDRs) are hypervariable regions present in the variable domains of the heavy chain and the variable domains of the light chain. Typically, the CDRs of the linked heavy chain and light chain of an antibody together form an antigen receptor. Typically, the three CDRs (CDR1, CDR2, and CDR3) are arranged non-consecutive within the variable domains. Since an antigen receptor typically comprises two variable domains (on two different polypeptide chains, namely, the heavy and light chains), there are six CDRs for each antigen receptor (heavy chain: CDRH1, CDRH2, and CDRH3; light chain: CDRL1, CDRL2, and CDRL3). A single antibody molecule typically has two antigen receptors and therefore contains twelve CDRs.The CDRs in the heavy and / or light chains can be separated by framework regions, where the framework regions (FRs) are regions in the variable domain that are less variable than the CDRs. For example, a chain (or each chain, respectively) may consist of four framework regions, separated by three CDRs. The heavy chain and light chain sequences of an exemplary antibody of the present invention, comprising three different CDRs on the heavy chain and three different CDRs on the light chain were determined. The amino acid positions of the CDRs were determined according to the IMGT numbering system (IMGT: http: / / www.imgt.org / ; cf. Lefranc, MP et al. (2009) Nucleic Acids Res. 37, D1006-D1012). Typically, the antibodies of the present invention bind to the hemagglutinin of influenza A virus. Thus, the antibodies of the present invention can neutralize influenza A virus infection. Based on the six CDR sequences as defined above, the antibodies of the present invention bind to the same epitopes of the influenza A virus hemagglutinin stem region (IAV HA) as MEDI8852 (Kallewaard NL, Corti D, Collins PJ, et al. Structure and Function Analysis of an Antibody Recognizing All Influenza A Subtypes. Cell. 2016; 166 (3):596-608), thereby providing the same broad protection against various influenza A serotypes of all influenza A subtypes. In addition, the antibody of the present invention includes two mutations in the constant region of the heavy chain (in the CH3 region): M428L and N434S. In this context, the amino acid positions have been numbered according to the EU numbering system recognized in the art. The EU index or EU index as in Kabat or UE numbering refers to the EU antibody numbering (Edelman GM, Cunningham BA, Gall WE, Gottlieb PD, Rutishauser U, Waxdal MJ. The covalent structure of an entire gammaG immunoglobulin molecule. Proc Natl Acad Sci U S A. 1969; 63(1):78-85; Kabat EA, National Institutes of Health (US) Office of the Director, “Sequences of Proteins of Immunological Interest”, 5th edition, Bethesda, MD : US Dept. of Health and Human Services, Public Health Service, National Institutes of Health, 1991, hereby entirely incorporated by reference). In some embodiments, the antibody of the present invention neutralizes influenza A infection at a dose, which does not exceed one-half of the dose required for neutralization of influenza A with a comparative antibody, which differs from said antibody only in that it does not contain the mutations M428L and N434S in the constant region of the heavy chain. In some embodiments, the dose of the antibody of the present invention does not exceed one-third of the dose required for neutralization of influenza A with said comparative antibody. In some embodiments, the dose of the antibody of the present invention does not exceed one-quarter of the dose required for neutralization of influenza A with said comparative antibody. In some embodiments, the dose of the antibody of the present invention does not exceed one-fifth of the dose required for neutralization of influenza A with said comparative antibody.In some embodiments, the antibody dose of the present invention does not exceed one-sixth of the dose required for neutralization of influenza A with said reference antibody. In some embodiments, the antibody dose of the present invention does not exceed one-seventh of the dose required for neutralization of influenza A with said reference antibody. In some embodiments, the antibody dose of the present invention does not exceed one-eighth of the dose required for neutralization of influenza A with said reference antibody. In some embodiments, the antibody dose of the present invention does not exceed one-ninth of the dose required for neutralization of influenza A with said reference antibody. In some embodiments, the antibody dose of the present invention does not exceed one-tenth of the dose required for neutralization of influenza A with said reference antibody.It is understood that for such comparative tests comparable neutralization tests (similar test assays, assay conditions, etc.) are used. For example, the same test (differing only in the antibodies to be tested) can be used to determine the antibody dose of the invention for neutralization of influenza A and to determine the comparative antibody dose for neutralization of influenza A. To study and measure virus infectivity (or neutralization) in the laboratory, experts in the field are familiar with various standard neutralization assays. For neutralization assays, animal viruses are typically propagated in cells and / or cell lines. For example, in a neutralization assay, cultured cells can be incubated with a specific amount of influenza A virus (IAV) in the presence (or absence) of the antibody being tested. Flow cytometry can be used as a readout, for example. Alternatively, other readouts can be performed. In certain embodiments, the antibody neutralizes viruses encoding the HA1 P11S, HA2 D46N, and / or HA2 N49T polymorphisms of the H3N2 hemagglutinin (H3 HA); and / or the N146D polymorphism of the H1N1 hemagglutinin (H1 HA). For example, the antibody may neutralize one or two of the HA1 P11S, HA2 D46N, or HA2 N49T of H3 HA. Specifically, the antibody may neutralize all three polymorphisms HA1 P11S, HA2 D46N, and HA2 N49T of H3 HA. In addition, the antibody may neutralize the N146D polymorphism of H1 HA. In some embodiments, the antibody neutralizes the HA1 P11S, HA2 D46N, and HA2 N49T polymorphisms of H3 HA; and the N146D polymorphism of H1 HA. For such polymorphisms, the reference for H1N1 is A / California / 07 / 2009 and the reference for H3N2 is A / Perth / 16 / 2009. In certain cases, the antibody neutralizes the HA1 P11S, HA2 D4 6N, and / or HA2 N4 9T polymorphisms of H3 HA; and / or the N146D polymorphism of H1 HA with an IC50 change of <2-fold relative to the HA of wild-type virus, particularly in side-by-side comparisons with wild-type virus. For example, the antibody may neutralize one or two of the HA1 P11S, HA2 D46N, or HA2 N49T polymorphisms of H3 HA with an IC50 change of <2-fold relative to the HA of wild-type virus, particularly in side-by-side comparisons with wild-type virus. Specifically, the antibody may neutralize all three of the HA1 P11S, HA2 D4 6N, and HA2 N4 9T polymorphisms of H3 HA with an IC50 change of <2-fold relative to the HA of wild-type virus, particularly in side-by-side comparisons with wild-type virus. In addition, the antibody can neutralize the N14 6D polymorphism of H1 HA with an IC50 change of <2-fold relative to the HA of the wild-type virus, particularly in side-by-side comparisons with the wild-type virus.In some embodiments, the antibody neutralizes the HA1 P11S, HA2 D46N, and HA2 N49T polymorphisms of H3 HA; and the N146D polymorphism of H1 HA, each with an IC50 change of <2-fold relative to the HA of the wild-type virus, particularly in a side-by-side comparison with the wild-type virus. In some embodiments, an antibody elicits a decreased anti-drug antibody (ADA) response compared to a comparative antibody that differs from such antibody only by not containing the M428L and N434S mutations in the heavy chain constant region. Specifically, the antibody may exhibit lower immunogenicity compared to a comparative antibody that differs from such antibody only by not containing the M428L and N434S mutations in the heavy chain constant region. As shown in examples of this specification, the antibody of the present invention surprisingly elicits a decreased anti-drug antibody (ADA) response and, thus, lower immunogenicity compared to an antibody without the M428L / N434S mutations. To assess the anti-drug antibody (ADA) response / immunogenicity, a person skilled in the art will be familiar with appropriate tests.Any such test may be selected as long as the antibody of the invention and a comparative antibody without the M428L / N434S mutation are tested side by side to allow for direct comparison. Exemplary tests are described in Examples 9 and 10 of this specification. In some embodiments, the antibodies of the present invention are human antibodies. In some embodiments, the antibodies of the present invention are monoclonal antibodies. For example, the antibodies of the present invention are human monoclonal antibodies. The antibodies of the present invention may be of any isotype (e.g., IgA, IgG, IgM, i.e., heavy chains, or ). For example, the antibody is of type IgG. Within the IgG isotype, the antibody may be of the subclass IgG1, IgG2, IgG3, or IgG4, e.g., IgG1. The antibodies of the present invention may have light chains or . In some embodiments, the antibody has kappa (κ) light chains. In some embodiments, the antibody is of type IgG1 and has light chains. In some embodiments, the antibody is of the human IgG1 type. The antibody may be of any allotype. The term allotype refers to the allelic variation found among IgG subclasses. For example, the antibody may be of the G1m1 (or G1m(a)) allotype, of the G1m2 (or G1m(x)) allotype, of the G1m3 (or G1m(f)) allotype, and / or of the G1m17 (or Gm(z)) allotype. The G1m3 and G1m17 allotypes are located at the same position in the CH1 domain (position 214 according to EU numbering). G1m3 corresponds to R214 (EU), while G1m17 corresponds to K214 (EU). The G1m1 allotype is located in the CH3 domain (at positions 356 and 358 (EU)) and refers to the substitutions E356D and M358L. The G1m2 allotype refers to the replacement of alanine at position 431 (EU) by glycine. The G1m1 allotype may be combined, for example, with the G1m3 or G1m17 allotypes. In some embodiments, the antibody is of the G1m3 allotype without G1m1 (G1m3,-1). In some embodiments, the antibody is of the G1m17,1 allotype. In some embodiments, the antibody is of the G1m3,1 allotype.In some embodiments, the antibody is of the G1m17 allotype without G1m1 (G1m17,-1). Optionally, this allotype may be combined (or not combined) with the G1m2, G1m27, or G1m28 allotype. For example, the antibody may be of the G1m17,1,2 allotype. In some embodiments, the antibody of the present invention comprises a heavy chain variable region comprising an amino acid sequence having 70% or more (i.e., 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity to SEQ ID NO: 7 and a light chain variable region comprising an amino acid sequence having at least 70% identity to SEQ ID NO: 8, wherein the CDR sequences are as defined above (heavy chain CDR1, CDR2, and CDR3 sequences) as specified in SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, and the light chain sequences CDR1, CDR2, and CDR3 as specified in SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively) are maintained. Sequence identity is usually calculated with respect to the full length of the reference sequence (i.e., the sequence disclosed in the application). Percentage identity, as referred to herein, can be determined, for example, using BLAST using the default parameters set by NCBI (the National Center for Biotechnology Information; http: / / www.ncbi.nlm.nih.gov / ) [Blosum 62 matrix; gap open penalty=11 and gap extension penalty=1]. A sequence variant has an altered sequence in which one or more amino acids in the reference sequence are deleted or substituted, and / or one or more amino acids are inserted into the sequence from the reference amino acid sequence. As a result of the changes, the amino acid sequence variant has an amino acid sequence that is at least 70% identical to the reference sequence. A variant sequence that is at least 70% identical has no more than 30 changes, i.e., any combination of deletions, insertions, or substitutions, per 100 amino acids of the reference sequence. In general, while it is possible to have non-conservative amino acid substitutions, they are usually conservative amino acid substitutions, where the substituted amino acid has similar structural or chemical properties to the corresponding amino acid in the reference sequence. For example, conservative amino acid substitutions involve the substitution of one aliphatic or hydrophobic amino acid, e.g., alanine, valine, leucine, and isoleucine, with another; the substitution of one hydroxyl-containing amino acid, e.g., serine and threonine, with another; the substitution of one acidic residue, e.g., glutamic acid or aspartic acid, with another; the substitution of one amide-containing residue, e.g., asparagine and glutamine, with another; the substitution of one aromatic residue, e.g., phenylalanine and tyrosine, with another; the substitution of one basic residue, e.g.,lysine, arginine and histidine, with others; and replacement of one small amino acid, for example, alanine, serine, threonine, methionine, and glycine, with another. Amino acid sequence insertions include amino and / or carboxyl-terminal fusions ranging in length from a single residue to polypeptides containing one hundred or more residues, as well as intrasequential insertions of single or multiple amino acid residues. Examples of terminal insertions include fusions to the N- or C-terminus of an amino acid sequence to a reporter molecule or enzyme. In some embodiments, the antibody of the present invention comprises a heavy chain variable region comprising an amino acid sequence having 75% or more (i.e., 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity to SEQ ID NO: 7 and a light chain variable region comprising an amino acid sequence having at least 75% identity to SEQ ID NO: 8, wherein the CDR sequence as defined above is retained.In some embodiments, the antibody of the present invention comprises a heavy chain variable region comprising an amino acid sequence having 80% or more (i.e., 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity to SEQ ID NO: 7 and a light chain variable region comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 8, wherein the CDR sequence as defined above is retained. In some embodiments, the antibody of the present invention comprises a heavy chain variable region comprising an amino acid sequence having 85% or more (i.e., 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity to SEQ ID NO: 7 and a light chain variable region comprising an amino acid sequence having at least 85% identity to SEQ ID NO: 8, wherein the CDR sequence as defined above is retained.In some embodiments, the antibody of the present invention comprises a heavy chain variable region comprising an amino acid sequence having 90% or more (i.e., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity to SEQ ID NO: 7 and a light chain variable region comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 8, wherein the CDR sequence as defined above is retained. In some embodiments, the antibody of the present invention comprises a heavy chain variable region comprising an amino acid sequence having 95% or more (i.e., 96%, 97%, 98%, 99% or more) identity to SEQ ID NO: 7 and a light chain variable region comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 8, wherein the CDR sequence as defined above is retained. In some embodiments, the antibody of the present invention comprises a heavy chain variable region comprising an amino acid sequence as set forth in SEQ ID NO: 7 and a light chain variable region comprising an amino acid sequence as set forth in SEQ ID NO: 8, wherein the CDR sequence as defined above is retained. In general, it is possible that the antibodies of the present invention may comprise one or more further mutations (in addition to M428L and N434S) in the Fc region (e.g., in the CH2 or CH3 regions). However, in some embodiments, the antibodies of the present invention do not comprise any further mutations other than M428L and N434S in its CH3 region (compared to the respective wild-type CH3 regions). In some embodiments, the antibody of the present invention does not comprise any further mutations other than M428L and N434S in its Fc region (compared to the respective wild-type Fc regions). As used herein, the term wild-type refers to a reference sequence, e.g., as it occurs in nature. As a specific example, the term wild-type may refer to the sequence with the highest prevalence that occurs in nature. In some embodiments, an antibody of the present invention comprises a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO: 9 and a light chain comprising an amino acid sequence as set forth in SEQ ID NO: 10. For example, an antibody of the present invention may have a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO: 9 and a light chain comprising an amino acid sequence as set forth in SEQ ID NO: 10. The antibodies of the present invention also include hybrid antibody molecules comprising six CDRs of the antibody of the invention as defined above and one or more CDRs of another antibody for the same or a different epitope or antigen. In some embodiments, the hybrid antibody comprises six CDRs of the antibody of the invention and six CDRs of another antibody for a different epitope or antigen. Variant antibodies are also within the scope of the invention. Therefore, variants of the sequence described in the application are also within the scope of the invention. Such variants include naturally occurring variants generated by somatic mutations in vivo during an immune response or in vitro in cultures of immortalized B cell clones. Alternatively, variants may arise due to degeneration of the genetic code or may be produced by errors in transcription or translation. The antibodies of the present invention may be provided in purified form. Typically, the antibodies will be present in a composition substantially free from other polypeptides, for example, where less than 90% (by weight), usually less than 60%, and more usually less than 50% of the composition consists of other polypeptides. Antibodies of the present invention may be immunogenic in non-human (or heterologous) hosts, for example, in mice. In particular, antibodies may possess idiotopes that are immunogenic in non-human hosts, but not in human hosts. In particular, antibodies of the invention for human use include those that cannot be readily isolated from hosts such as mice, goats, rabbits, rats, non-primate mammals, etc. and generally cannot be obtained by humanization or from xeno-mice. Nuclear Acid In another aspect, the present invention also provides nucleic acid molecules comprising polynucleotides encoding antibodies according to the present invention as described above. In certain embodiments, a nucleic acid molecule comprises: (i) a polynucleotide comprising a nucleotide sequence as set out in SEQ ID NO: 12; or a nucleotide sequence having 70% or more (i.e. 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity on SEQ ID NO: 12, a nucleotide sequence encoding a CDR sequence as defined above; and (ii) a polynucleotide comprising a nucleotide sequence as set forth in SEQ ID NO: 13; or a nucleotide sequence having 70% or more (e.g. 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity to SEQ ID NO: 13, a nucleotide sequence encoding a CDR sequence as defined above. In some embodiments, the nucleic acid molecule comprises: (i) a polynucleotide comprising a nucleotide sequence as set forth in SEQ ID NO: 14; or a sequence nucleotides that have 70% or more (i.e. 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity to the SEQ ID NO: 14, a nucleotide sequence encoding a CDR sequence as defined above and the M428L and N434S mutations in the constant region; and (ii) a polynucleotide comprising a nucleotide sequence as set forth in SEQ ID NO: 15; or a nucleotide sequence having 70% or more (e.g. 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity to SEQ ID NO: 15, the nucleotide sequence encoding the CDR sequence as defined above and the M428L and N434S mutations in the constant region. Examples of nucleic acid and / or polynucleotide molecules include, for example, recombinant polynucleotides, vectors, oligonucleotides, RNA molecules such as rRNA, mRNA, miRNA, siRNA, or tRNA, or DNA molecules such as cDNA. The nucleic acids may encode the light chains and / or heavy chains of the antibodies of the present invention. In other words, the light chains and heavy chains of the antibody may be encoded by the same nucleic acid molecule (e.g., in a bicistronic manner). Alternatively, the light chains and heavy chains of the antibody may be encoded by different nucleic acid molecules. Due to the redundancy of the genetic code, the present invention also comprises sequence variants of a nucleic acid sequence, which encode the same amino acid sequence. The polynucleotide encoding the antibody (or the complete nucleic acid molecule) may be optimized for antibody expression. For example, codon optimization of the nucleotide sequence may be used to improve translation efficiency in an expression system for antibody production. The exemplary nucleic acid sequences according to SEQ ID NO. 12, 13, 14 and 15 are sequences that may be codon optimized for expression of the exemplary antibody FluAB_MLNS. In addition, the nucleic acid molecule may comprise heterologous elements (i.e., elements, which in nature do not occur in the same nucleic acid molecule as the coding sequence for (heavy or light chain) of the antibody. For example, the nucleic acid molecule may comprise heterologous promoters, heterologous enhancers, heterologous UTRs (e.g., for optimal translation / expression), heterologous poly-A tails, and the like. A nucleic acid molecule is a molecule composed of nucleic acid components. The term nucleic acid molecule usually refers to a DNA or RNA molecule. It can be used synonymously with the term polynucleotide, i.e., a nucleic acid molecule may consist of a polynucleotide that codes for an antibody. Alternatively, a nucleic acid molecule may also consist of further elements in addition to the polynucleotide that codes for an antibody. Typically, a nucleic acid molecule is a polymer composed of or composed solely of nucleotide monomers covalently linked to each other by phosphodiester bonds of a sugar / phosphate backbone. The term nucleic acid molecule also includes modified nucleic acid molecules, such as base modifications, sugar modifications, or backbone modifications, etc., such as DNA or RNA molecules. In general, nucleic acid molecules can be manipulated to insert, delete, or modify specific nucleic acid sequences. These modifications include, but are not limited to, introducing restriction sites, altering codon usage, adding or optimizing transcriptional and / or translational regulatory sequences, etc. It is also possible to modify nucleic acids to alter the encoded amino acids. For example, it may be useful to introduce one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) amino acid substitutions, deletions, and / or insertions into the amino acid sequence of an antibody. Such point mutations may modify effector function, antigen-binding affinity, post-translational modification, immunogenicity, etc. They may introduce amino acids for covalent attachment (e.g., labeling) or may introduce tags (e.g., for purification purposes).Alternatively, mutations in the nucleic acid sequence may be silent, that is, not reflected in the amino acid sequence due to the redundancy of the genetic code. In general, mutations may be introduced at specific sites or may be introduced randomly, followed by selection (e.g., molecular evolution). For example, one or more nucleic acids encoding one of the light or heavy chains of an antibody (example) of the present invention may be mutated randomly or directed to introduce different properties in the encoded amino acids. Such changes may be the result of an iterative process in which the initial changes are retained and new changes at other nucleotide positions are introduced. Next, the changes achieved in independent steps can be combined. In some embodiments, the polynucleotide encoding the antibody, or an antigen-binding fragment thereof, (or a (complete) nucleic acid molecule) may be codon optimized. Those skilled in the art are familiar with various tools for codon optimization, such as those described in: Ju Xin Chin, Bevan KaiSheng Chung, Dong-Yup Lee, Codon Optimization OnLine (COOL): a web-based multi-objective optimization platform for synthetic gene design, Bioinformatics, Volume 30, Issue 15, 1 August 2014, Pages 2210-2212; or in: Grote A, Hiller K, Scheer M, Munch R, Nortemann B, Hempel DC, Jahn D, JCat: a novel tool to adapt codon usage of a target gene to its potential expression host. Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W526-31; or, for example, Genscript's OptimumGeneTMalgorithm (as described in US 2011 / 0081708 A1). The present invention also provides a combination of first and second nucleic acid molecules, wherein the first nucleic acid molecule comprises a polynucleotide encoding a heavy chain of an antibody of the present invention; and the second nucleic acid molecule comprises a polynucleotide encoding a corresponding light chain of the same antibody. The above description of the (general) characteristics of the nucleic acid molecules of the present invention applies with respect to the first and second nucleic acid molecules of the combination. For example, one or both of the polynucleotides encoding the heavy and / or light chains of the antibody, or antigen-binding fragments thereof, may be codon-optimized. In certain embodiments, the combination of nucleic acid molecules comprises: (i) the first nucleic acid molecule consisting of a polynucleotide encoding the heavy chain of an antibody, the polynucleotide consisting of a sequence of nucleotides as specified in SEQ ID NO: 12; or a nucleotide sequence that has 70% or more (e.g. 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity to the SEQ ID NO: 12, a nucleotide sequence encoding a CDR sequence as defined above; and (ii) a second nucleic acid molecule comprising a polynucleotide encoding an antibody light chain, the polynucleotide comprising a nucleotide sequence as specified in SEQ ID NO: 13; or a nucleotide sequence that has 70% or more (e.g. 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity to the SEQ ID NO: 13, the nucleotide sequence encoding the CDR sequence as defined above. In some embodiments, the combination of nucleic acid molecules comprises: (i) a first nucleic acid molecule comprising a polynucleotide encoding an antibody heavy chain, the polynucleotide comprising a nucleotide sequence as set forth in SEQ ID NO: 14; or a sequence nucleotides that have 70% or more (e.g. 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity to the SEQ ID NO: 14, the nucleotide sequence encoding the CDR sequence as defined above and the M428L mutation and N434S in the constant region; and (ii) a second nucleic acid molecule comprising a polynucleotide encoding an antibody light chain, the polynucleotide comprising a nucleotide sequence as set forth in SEQ ID NO: 15; or a nucleotide sequence having 70% or more (e.g., 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity to SEQ ID NO: 15, the nucleotide sequence encoding the CDR sequence as defined above and the M428L and N434S mutations in the constant region. Vector Further included within the scope of the present invention are vectors, for example, expression vectors, comprising nucleic acid molecules according to the present invention or combinations of nucleic acid molecules according to the present invention (e.g., in a bicistronic manner). Typically, the vectors comprise nucleic acid molecules as described above or combinations of nucleic acid molecules as described above (e.g., in a bicistronic manner). The present invention also provides a combination of first and second vectors, wherein the first vector comprises a first nucleic acid molecule as described above (for a combination of nucleic acid molecules) and the second vector comprises a second nucleic acid molecule as described above (for a combination of nucleic acid molecules). A vector is typically a recombinant nucleic acid molecule, i.e., a nucleic acid molecule that does not occur in nature. Thus, a vector may comprise heterologous elements (i.e., sequence elements of different origins in nature). For example, a vector may comprise multiple cloning sites, heterologous promoters, heterologous enhancers, heterologous selection markers (to identify cells containing the vector compared to cells not containing the vector) and the like. A vector in the context of the present invention is suitable for incorporating or storing a desired nucleic acid sequence. Such a vector may be a storage vector, an expression vector, a cloning vector, a transfer vector, etc. A storage vector is a vector that allows for the convenient storage of nucleic acid molecules. Thus, a vector may comprise a sequence corresponding, for example, to (the heavy and / or light chains of) a desired antibody according to the present invention.Expression vectors can be used for the production of expression products such as RNA, e.g., mRNA, or peptides, polypeptides, or proteins. For example, an expression vector may comprise sequences necessary for the transcription of a sequence of the vector, such as a (heterologous) promoter sequence. A cloning vector is typically a vector containing a cloning site, which can be used to insert a nucleic acid sequence into the vector. A cloning vector may be, for example, a plasmid vector or a bacteriophage vector. A transfer vector may be a vector suitable for transferring nucleic acid molecules into cells or organisms, such as a viral vector. A vector in the context of the present invention may be, for example, an RNA vector or a DNA vector. For example, a vector in the sense of the present application comprises a cloning site, a selection marker, such as an antibiotic resistance factor, and a sequence suitable for vector amplification, such as an origin of replication. A vector in the context of the present application may be a plasmid vector. Cell In a further aspect, the present invention also provides antibodies expressing cells according to the present invention; and / or comprising vectors according to the present invention. Examples of such cells include, but are not limited to, eukaryotic cells, e.g., yeast cells, animal or plant cells, or prokaryotic cells, including E. coli. In some embodiments, the cells are mammalian cells, such as mammalian cell lines. Examples include human cells, CHO cells, HEK293T cells, PER.C6 cells, NS0 cells, human liver cells, myeloma cells, or hybridoma cells. Cells can be transfected with vectors according to the present invention, for example with expression vectors. The term transfection refers to the introduction of nucleic acid molecules, such as DNA or RNA molecules (e.g. mRNA), into cells, e.g. into eukaryotic or prokaryotic cells. In the context of the present invention, the term transfection includes any method known to the skilled person for introducing nucleic acid molecules into cells, such as into mammalian cells. Such methods include, for example, electroporation, lipofection, e.g. based on cationic lipids and / or liposomes, calcium phosphate precipitation, nanoparticle-based transfection, virus-based transfection, or transfection based on cationic polymers, such as DEAEdextran or polyethylenimine etc. In some embodiments, the introduction is non-viral. Furthermore, the cells of the present invention may be stably or transiently transfected with the vector according to the present invention, e.g., to express the antibody according to the present invention. In some embodiments, the cells are stably transfected with the vector according to the present invention encoding the antibody according to the present invention. In other embodiments, the cells are transiently transfected with the vector according to the present invention encoding the antibody according to the present invention. Thus, the present invention also provides recombinant host cells, which heterologously express the antibodies of the invention or antigen-binding fragments thereof. For example, the cells may be of a species other than the antibody (e.g., CHO cells expressing human antibodies). In some embodiments, the cell type of the cells does not express such antibodies in nature. In addition, the host cells may introduce post-translational modifications (PTMs; e.g., glycosylation) to the antibody that are not present in its native state. Such PTMs may result in functional differences (e.g., decreased immunogenicity). Thus, the antibodies of the invention, or antigen-binding fragments thereof, may have post-translational modifications, which differ from naturally produced antibodies (e.g., antibodies from the human immune response). Antibody Production Antibodies according to the present invention may be prepared by any method known in the art. For example, general methodologies for preparing monoclonal antibodies using hybridoma technology are well known (Kohler, G. and Milstein, C., 1975; Kozbar et al. 1983). In some embodiments, an alternative EBV immortalization method described in WO2004 / 076677 is used. In some embodiments, the method described in WO 2004 / 076677, which is incorporated herein by reference, is used. In this method, antibody-producing B cells of the present invention are transformed with EBV and a polyclonal B-cell activator. Additional stimulants for cellular growth and differentiation may optionally be added during the transformation step to further increase efficiency. These stimulants may be cytokines such as IL-2 and IL-15. In one aspect, IL-2 is added during the immortalization step to further increase immortalization efficiency, but its use is not essential. Immortalized B cells produced using this method may then be cultured using methods known in the art and antibodies isolated therefrom. Another exemplary method is described in WO 2010 / 046775. In this method, plasma cells are cultured in limited numbers, or as single plasma cells in microwell culture plates. Antibodies can be isolated from the plasma cell culture. RNA can then be extracted from the plasma cell culture and PCR can be performed using methods known in the art. The VH and VL regions of the antibodies can be amplified by RT-PCR (reverse transcriptase PCR), sequenced, and cloned into an expression vector that is then transfected into HEK293T cells or other host cells. Cloning of the nucleic acid in the expression vector, transfection of host cells, culture of the transfected host cells, and isolation of the resulting antibodies can be performed using any method known to one skilled in the art. Antibodies can be further purified, if desired, using filtration, centrifugation, and various chromatographic methods such as HPLC or affinity chromatography. Techniques for purifying antibodies, such as monoclonal antibodies, including techniques for producing pharmaceutical-grade antibodies, are well known in the field. Standard molecular biology techniques can be used to generate DNA sequences encoding the antibodies of the present invention. The desired DNA sequence can be synthesized in whole or in part using oligonucleotide synthesis techniques. Site-directed mutagenesis and polymerase chain reaction (PCR) techniques can be used as appropriate. Any suitable host cell / vector system may be used for the expression of the DNA sequence encoding the antibody molecule of the present invention. Eukaryotic, e.g., mammalian, host cell expression systems may be used for the production of antibody molecules, such as complete antibody molecules. Suitable mammalian host cells include, but are not limited to, CHO, HEK293T, PER.C6, NS0, myeloma, or hybridoma cells. In another embodiment, the expression of the DNA sequence encoding the antibody molecule of the present invention to be used may be expressed in prokaryotic cells, including, but not limited to, E. coli. The present invention also provides a process for the production of antibody molecules according to the present invention comprising culturing (heterologous) host cells comprising a vector encoding a nucleic acid of the present invention under conditions suitable for protein expression from DNA encoding the antibody molecules of the present invention, and isolating the antibody molecules. To produce antibodies containing both heavy and light chains, cell lines can be transfected with two vectors, one encoding the light chain polypeptide and the other encoding the heavy chain polypeptide. Alternatively, a single vector can be used, one containing sequences encoding both the light and heavy chain polypeptides. Antibodies according to the present invention may be produced by (i) expressing nucleic acid sequences according to the present invention in host cells, e.g., by using vectors according to the present invention, and (ii) isolating the expressed antibody product. In addition, the method may include (iii) purifying the isolated antibody. Transformed B cells and cultured plasma cells may be screened for the production of antibodies with desired specificity or function. The screening step may be performed by immunoassay, e.g., ELISA, by staining of tissues or cells (including transfected cells), by neutralization assays, or by any of a number of other methods known in the art to identify the desired specificity or function. The assay may select on the basis of simple recognition of one or more antigens, or may select on the additional basis of the desired function, e.g., to select neutralizing antibodies rather than simply antigen-binding antibodies, to select antibodies that may alter characteristics of the target cell, such as its signaling cascade, its shape, its growth rate, its ability to influence other cells, its response to the influence of other cells or other reagents or to changes in conditions, its differentiation status, etc. Individual transformed B cell clones can then be produced from a culture of positively transformed B cells. The cloning step of separating individual clones from a mixture of positive cells can be accomplished using limiting dilution, micromanipulation, single-cell deposition by cell sorting, or other methods known in the art. Nucleic acids from cultured plasma cells can be isolated, cloned and expressed in HEK293T cells or other known host cells using methods known in the art. Immortalized B cell clones or transfected host cells of the present invention may be used in various ways e.g., as a source of monoclonal antibodies, as a source of nucleic acid (DNA or mRNA) encoding the monoclonal antibody of interest, for research, etc. The present invention also provides compositions comprising immortalized memory B cells or transfected host cells that produce antibodies according to the present invention. Immortalized B cell clones or cultured plasma cells of the present invention may also be used as a nucleic acid source for cloning antibody genes for subsequent recombinant expression. Expression from a recombinant source may be more common for pharmaceutical purposes than expression from B cells or hybridomas, for reasons of stability, reproducibility, ease of culture, etc. Thus the present invention also provides a method for making recombinant cells, comprising the steps of: (i) obtaining one or more nucleic acids (e.g., heavy and / or light chain mRNA) from a clone of B cells or cultured plasma cells encoding an antibody of interest; (ii) inserting the nucleic acids into an expression vector and (iii) transfecting the vector into a (heterologous) host cell to enable expression of the desired antibody in said host cell. Similarly, the present invention also provides a method for making recombinant cells, comprising the steps of: (i) sequencing the nucleic acid of a clone of cultured B cells or plasma cells encoding the desired antibody; and (ii) using the sequence information from step (i) to prepare the nucleic acid for insertion into a host cell to enable expression of the desired antibody in that host cell. The nucleic acid may, but need not, be manipulated between steps (i) and (ii) to introduce restriction sites, to alter codon usage, and / or to optimize transcriptional and / or translational regulatory sequences. Furthermore, the present invention also provides a method of preparing transfected host cells, comprising the step of transfecting the host cells with one or more nucleic acids encoding desired antibodies, wherein the nucleic acids are nucleic acids derived from immortalized B cell clones or cultured plasma cells of the present invention. So the procedure for first preparing nucleic acid and then using it to transfect host cells may be performed at different times by different people in different places (e.g., in different countries). The recombinant cells of the present invention can then be used for expression and culture purposes. They are particularly useful for antibody expression for large-scale pharmaceutical production. They can also be used as active ingredients of pharmaceutical compositions. Suitable culture techniques can be used, including but not limited to static culture, roller bottle culture, ascitic fluid, hollow fiber bioreactor cartridges, modular minifermenters, stirred tanks, microcarrier culture, ceramic core perfusion, etc. Methods for obtaining and sequencing immunoglobulin genes from B cells or plasma cells are well known in the field (e.g., see Chapter 4 of Kuby Immunology, 4th edition, 2000). The transfected host cells may be eukaryotic cells, including yeast and animal cells, particularly mammalian cells (e.g., CHO cells, NS0 cells, human cells such as PER.C6 or HKB 11 cells, myeloma cells, or human liver cells), as well as plant cells. In some embodiments, the transfected host cells may be prokaryotic cells, including E. coli. In some embodiments, the transfected host cells are mammalian cells, such as human cells. In some embodiments, the expression host may glycosylate antibodies of the invention, particularly with carbohydrate structures that are not immunogenic to humans. In some embodiments, the transfected host cells may be able to grow in serum-free media. In further embodiments the transfected host cells may be able to grow in culture in the absence of animal-derived products. The transfected host cells may also be cultured to provide cell lines. The present invention also provides a method for making one or more nucleic acid molecules (e.g., heavy and light chain genes) encoding a desired antibody, comprising the steps of: (i) preparing an immortalized B cell clone or cultured plasma cells in accordance with the invention; (ii) obtaining from the B cell clone or cultured plasma cells nucleic acid encoding the desired antibody. Further, the present invention provides a method for obtaining a nucleic acid sequence encoding the desired antibody, comprising the steps of: (i) preparing an immortalized B cell clone or cultured plasma cells in accordance with the invention; (ii) sequencing the nucleic acid from the B cell clone or cultured plasma cells encoding the desired antibody. The present invention further provides a method for preparing a nucleic acid molecule encoding a desired antibody, comprising the step of obtaining a nucleic acid obtained from a transformed B cell clone or cultured plasma cell of the invention. Thus the procedure for first obtaining a B cell clone or cultured plasma cell, and then obtaining a nucleic acid from the B cell clone or cultured plasma cell may be carried out at different times by different persons in different places (e.g., different countries). The present invention also comprises a method for preparing antibodies (e.g., for pharmaceutical use) according to the present invention, comprising the steps of: (i) obtaining and / or sequencing one or more nucleic acids (e.g., heavy and light chain genes) from selected B cell clones or cultured plasma cells expressing the desired antibody; (ii) introducing the nucleic acid into or using the nucleic acid sequence to prepare an expression vector; (iii) transfecting host cells capable of expressing the desired antibody; (iv) culturing or subculturing the transfected host cells under conditions in which the desired antibody is expressed; and, optionally, (v) purifying the desired antibody. The present invention also provides a method for producing a desired antibody comprising the steps of: culturing or subculturing a transfected host cell population, i.e. a stably transfected host cell population, under conditions in which the desired antibody is expressed and, optionally, purifying the desired antibody, wherein said transfected host cell population has been prepared by (i) providing a nucleic acid encoding a selected desired antibody produced by a clone of cultured B cells or plasma cells prepared as described above, (ii) inserting the nucleic acid into an expression vector, (iii) transfecting the vector in host cells capable of expressing the desired antibody, and (iv) culturing or subculturing the transfected host cells comprising the inserted nucleic acid to produce the desired antibody.Thus the procedures for first preparing recombinant host cells and then culturing them to express antibodies may be performed at very different times by different people in different places (e.g., in different countries). The present invention also provides a method of decreasing the immunogenicity of an antibody comprising heavy chain sequences CDR1, CDR2, and CDR3 as set forth in SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3; light chain sequences CDR1, CDR2, and CDR3 as set forth in SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6; and the method comprising the step of introducing M428L and N434S mutations in the constant region of the heavy chain of the antibody. The mutations can be achieved as described above. As shown in examples of this specification, the antibody of the present invention surprisingly exhibits only very low immunogenicity, specifically lower immunogenicity compared to the antibody without the M428L / N434S mutations. Therefore, introducing such mutations into the antibody decreases the immunogenicity of the antibody. Pharmaceutical Composition The present invention also provides pharmaceutical compositions comprising one or more of: (i) antibodies according to the present invention; (ii) nucleic acids encoding antibodies according to the present invention; (iii) a vector comprising a nucleic acid according to the present invention; and / or (iv) cells expressing antibodies according to the present invention or comprising a vector according to the present invention and, optionally, a pharmaceutically acceptable diluent or carrier. In other words, the present invention also provides a pharmaceutical composition comprising an antibody according to the present invention, a nucleic acid according to the present invention, a vector according to the present invention and / or cells according to the present invention. The pharmaceutical composition may optionally also contain pharmaceutically acceptable carriers, diluents and / or excipients. While the carrier or excipient may facilitate administration, it should not induce antibody production that is harmful to the individual receiving the composition. It should also be non-toxic. Suitable carriers may be large, slowly metabolized macromolecules such as proteins, polypeptides, liposomes, polysaccharides, polylactic acid, polyglycolic acid, polymeric amino acids, copolymers of amino acids and inactivated viral particles. In some embodiments, the pharmaceutically acceptable carrier, diluent and / or excipient in the pharmaceutical composition according to the present invention are not active components with respect to influenza A virus infection. Pharmaceutically acceptable salts may be used, for example mineral acid salts, such as hydrochloride, hydrobromide, phosphate and sulfate, or organic acid salts, such as acetate, propionate, malonate and benzoate. Pharmaceutically acceptable carriers in an ancillary pharmaceutical composition may contain liquids such as water, salt, glycerol, and ethanol. In addition, excipients, such as wetting or emulsifying agents or pH buffering agents, may be present in the composition. These carriers enable the pharmaceutical composition to be formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, and suspensions, for ingestion by the subject. The pharmaceutical compositions of the present invention can be prepared in various forms. For example, the compositions can be prepared for injection, either as a liquid solution or suspension. Solid forms suitable for solution in, or suspension in, a liquid vehicle prior to injection can also be prepared (e.g., lyophilized compositions, similar to Synagis™ and Herceptin®, for reconstitution with sterile water containing a preservative). The compositions can be prepared for topical administration, e.g., as an ointment, cream, or powder. The compositions can be prepared for oral administration, e.g., as tablets or capsules, as a spray, or as a syrup (with optional flavoring). The compositions can be prepared for pulmonary administration, e.g., as an inhaler, using a fine powder or a spray. The compositions can be prepared as suppositories or pessaries. The compositions can be prepared for nasal, aural, or ocular administration, e.g., as drops.The composition may be in the form of a kit, designed so that the combined composition is dissolved immediately before administration to a subject. For example, lyophilized antibodies may be administered in a kit with sterile water or sterile buffer. In some embodiments, the active (sole) ingredient in the composition is an antibody according to the invention. As such, it may be susceptible to degradation in the gastrointestinal tract. Therefore, if the composition is to be administered via a route involving the gastrointestinal tract, the composition may contain a substance that protects the antibody from degradation but releases the antibody after absorption from the gastrointestinal tract. A comprehensive discussion of pharmaceutically acceptable carriers is available in: Gennaro (2000) Remington: The Science and Practice of Pharmacy, 20th edition, ISBN: 0683306472 . The pharmaceutical compositions of the present invention generally have a pH between 5.5 and 8.5, in some embodiments this may be between 6 and 8, for example, about 7. The pH may be maintained by using a buffer. The compositions may be sterile and / or pyrogen-free. The compositions may be isotonic to humans. In some embodiments, the pharmaceutical compositions of the present invention are provided in hermetically sealed containers. Within the scope of the present invention are compositions that exist in several forms of administration; such forms include, but are not limited to, forms suitable for parenteral administration, for example by injection or infusion, for example by bolus injection or continuous infusion. If the product is for injection or infusion, it may be in the form of a suspension, solution or emulsion in an oily or aqueous vehicle and may contain formulatory agents, such as suspending agents, preservatives, stabilizers and / or dispersing agents. Alternatively, antibodies may be in dry form, to be reconstituted before use with a suitable sterile fluid. A vehicle is generally understood to be a material suitable for storing, transporting, and / or administering a compound, such as a pharmaceutically active compound, in particular an antibody according to the present invention. For example, the vehicle may be a physiologically acceptable liquid suitable for storing, transporting, and / or administering a pharmaceutically active compound, in particular an antibody according to the present invention. Once formulated, the compositions of the invention may be administered directly to a subject. In some embodiments, the compositions are adapted for administration to mammals, e.g., human subjects. The pharmaceutical compositions of the present invention may be administered by a number of routes including, but not limited to, oral, intravenous, intramuscular, intra-arterial, intramedullary, intraperitoneal, intrathecal, intraventricular, transdermal, transcutaneous, topical, subcutaneous, intranasal, enteral, sublingual, intravaginal or rectal routes. Hyposprays may also be used to administer the pharmaceutical compositions of the present invention. Optionally, the pharmaceutical compositions may be prepared for oral administration, e.g., as tablets, capsules and the like, for topical administration, or as an injection, e.g., as a liquid solution or suspension. In some embodiments, the pharmaceutical compositions are injectable. Solid forms suitable for solution in, or suspension in, a liquid vehicle prior to injection are also included, e.g., the pharmaceutical compositions may be in lyophilized form. For injections, e.g., intravenous, cutaneous, or subcutaneous injections, or injections at the site of injury, the active ingredient may be a parenterally acceptable aqueous solution that is pyrogen-free and has a suitable pH, isotonicity, and stability. Those with relevant expertise in the art are well-equipped to prepare suitable solutions using, for example, isotonic vehicles such as Sodium Chloride Injection, Ringer's Injection, Ringer's Lactate Injection. Preservatives, stabilizers, buffers, antioxidants, and / or other additives may be included, as required. Whether it is antibodies, peptides, nucleic acid molecules, or other pharmaceutically useful compounds according to the present invention that are to be administered to an individual, the administration is typically in a “prophylactically effective amount” or “therapeutically effective amount” (as the case may be), sufficient to demonstrate benefit to the individual.The actual amount administered, and the rate and timing of administration, will depend on the nature and severity of the condition being treated. For injection, the pharmaceutical composition according to the invention may be administered, for example, in a pre-filled syringe. The inventive pharmaceutical compositions as defined above may also be administered orally in any orally acceptable dosage form, including, but not limited to, capsules, tablets, aqueous suspensions, or solutions. In the case of tablets for oral use, commonly used carriers include lactose and corn starch. Lubricating agents, such as magnesium stearate, are also typically added. For oral administration in capsule form, useful diluents include lactose and dried corn starch. When an aqueous suspension is required for oral use, the active ingredient, i.e., the inventive carrier-cargo conjugate molecule as defined above, is combined with emulsifying and suspending agents. If desired, certain sweetening, flavoring, or coloring agents may also be added. Inventive pharmaceutical compositions may also be administered topically, particularly when the treatment target includes areas or organs readily accessible by topical application, for example. including accessible epithelial tissue. Suitable topical formulations are readily prepared for each of these areas or organs. For topical application, the inventive pharmaceutical composition may be formulated in a suitable ointment, containing the inventive pharmaceutical composition, in particular its components as defined above, suspended or dissolved in one or more vehicles. Vehicles for topical administration include, but are not limited to, mineral oil, liquid petrolatum, white petrolatum, propylene glycol, polyoxyethylene, polyoxypropylene compounds, emulsifying waxes and water. Alternatively, the inventive pharmaceutical composition may be formulated in a suitable lotion or cream. In the context of the present invention, suitable vehicles include, but are not limited to, mineral oil, sorbitan monostearate, polysorbate 60, cetyl ester wax, cetearyl alcohol, 2-octyldodecanol, benzyl alcohol and water. The dosage regimen may be a single-dose schedule or a multiple-dose schedule. Specifically, the pharmaceutical composition may be administered as a single-dose product. In some embodiments, the amount of antibody in the pharmaceutical composition, particularly when provided as a single-dose product, may not exceed 200 mg, for example, 100 mg or 50 mg. For example, the pharmaceutical composition according to the present invention may be administered daily, e.g. once or several times a day, e.g. once, twice, three times or four times a day, for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 days or more, e.g. daily for 1, 2, 3, 4, 5, 6 months. In some embodiments, the pharmaceutical composition according to the present invention may be administered weekly, e.g. once or twice a week, for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 or more weeks, e.g. weekly for 1, 2, 3, 4, 5, 6, 8, 9, 10, 11, or 12 months or weekly for 2, 3, 4, or 5 years. In addition, the pharmaceutical composition according to the invention may be administered monthly, e.g., once per month or every second month for 1, 2, 3, 4, or 5 years or more. Administration may also continue for life. In some embodiments, only a single administration is also envisaged, particularly in connection with certain indications, e.g., for the prophylaxis of influenza A virus infection. For example, a single administration (single dose) is given and further doses may be given at one or more subsequent time points, when the antibody titer is insufficient or deemed insufficient for protection. For a single dose, e.g., a daily, weekly or monthly dose, the amount of antibodies in the pharmaceutical composition according to the present invention, may not exceed 1 g or 500 mg. In some embodiments, for a single dose, the amount of antibodies in the pharmaceutical composition according to the present invention, may not exceed 200 mg, or 100 mg. For example, for a single dose, the amount of antibodies in the pharmaceutical composition according to the present invention, may not exceed 50 mg. Pharmaceutical compositions typically include an effective amount of one or more antibodies of the present invention, that is, an amount sufficient to treat, ameliorate, attenuate, mitigate, or prevent the desired disease or condition, or to exhibit a detectable therapeutic effect. Therapeutic effects may also include the reduction or attenuation of pathogenic potency or physical symptoms. The appropriate effective amount for any particular subject will depend on its size, weight, and health, the nature and extent of its condition, and the therapy or combination of therapies selected for administration. The effective amount for a particular situation is determined by routine experimentation and in the judgment of a physician. For purposes of the present invention, the effective dose may generally be from about 0.005 to about 100 mg / kg, for example, from about 0.0075 to about 50 mg / kg, or from about 0.01 to about 10 mg / kg.In some embodiments, the effective dose will be from about 0.02 to about 5 mg / kg, of the antibody of the present invention (e.g., the amount of antibody in the pharmaceutical composition) in relation to the body weight (e.g., in kg) of the individual to whom it is administered. In addition, the pharmaceutical composition according to the present invention may also comprise additional active components, which may be further antibodies or components, which are not antibodies. For example, the pharmaceutical composition may comprise one or more antivirals (which are not antibodies). In addition, the pharmaceutical composition may also comprise one or more antibodies (which are not in accordance with the invention), for example, antibodies to other influenza virus antigens (other than hemagglutinin) or antibodies to other influenza viruses (for example, to influenza B virus or to influenza C virus). Thus, the pharmaceutical composition according to the present invention may comprise one or more additional active components. The antibodies according to the present invention may be present either in the same pharmaceutical composition as the additional active component or, alternatively, the antibodies according to the present invention may comprise a first pharmaceutical composition and the additional active component may comprise a second pharmaceutical composition different from the first pharmaceutical composition. Thus, if more than one additional active component is considered, each additional active component and the antibodies according to the present invention may comprise a different pharmaceutical composition. Such different pharmaceutical compositions may be administered either in combination / simultaneously or at separate times or at separate locations (e.g., separate body parts). Antibodies according to the present invention and additional active components may provide additional therapeutic effects, such as synergistic therapeutic effects. The term synergistic is used to describe the combined effect of two or more active substances that is greater than the sum of the individual effects of each active substance. Thus, if the combined effect of two or more substances results in “synergistic inhibition” of an activity or process, it is intended that the inhibition of that activity or process is greater than the sum of the inhibitory effects of the individual active substances. The term synergistic therapeutic effect refers to a therapeutic effect observed with a combination of two or more therapies where the therapeutic effect (as measured by one of a number of parameters) is greater than the sum of the individual therapeutic effects observed with each individual therapy. In some embodiments, the compositions of the invention may include antibodies of the invention, wherein the antibodies may constitute at least 50% by weight (e.g., 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) of the total protein in the composition. In the compositions of the invention, the antibodies may be in purified form. The present invention also provides a method of preparing a pharmaceutical composition comprising the steps of: (i) preparing an antibody of the invention; and (ii) mixing the purified antibody with one or more pharmaceutically acceptable carriers. In another embodiment, a method of preparing a pharmaceutical composition comprises the step of: mixing an antibody with one or more pharmaceutically acceptable carriers, wherein the antibody is a monoclonal antibody obtained from transformed B cells or cultured plasma cells of the invention. As an alternative to administering antibodies or B cells for therapeutic purposes, it is possible to administer nucleic acids (usually DNA) encoding monoclonal antibodies derived from cultured B cells or plasma cells to a subject, so that the nucleic acids can be expressed in the subject in situ to provide the desired therapeutic effect. Appropriate gene therapy and nucleic acid delivery vectors are known in the art. Pharmaceutical formulations may include antimicrobials, particularly when packaged in multiple-dose formats. They may contain detergents, such as Tween (polysorbate), such as Tween 80. Detergents are generally present at low levels, such as less than 0.01%. The formulation may also include sodium salts (e.g., sodium chloride) to provide tonicity. For example, a concentration of 10±2 mg / ml NaCl is typical. Furthermore, pharmaceutical compositions may comprise sugar alcohols (e.g., mannitol) or disaccharides (e.g., sucrose or trehalose) for example, about 15-30 mg / ml (e.g., 25 mg / ml), especially if they are to be lyophilized or if they include materials reconstituted from lyophilized materials. The pH of the composition for lyophilization may be adjusted between 5 and 8, or between 5.5 and 7, or about 6.1 before lyophilization. The compositions of the present invention may also comprise one or more immunoregulatory agents. In some embodiments, the one or more immunoregulatory agents include(s) adjuvants. Treatment and Medical Uses In a further aspect, the present invention provides the use of antibodies according to the present invention, nucleic acids according to the present invention, vectors according to the present invention, cells according to the present invention or pharmaceutical compositions according to the present invention in the prophylaxis and / or treatment of influenza A virus infection; or in (ii) the diagnosis of influenza A virus infection. Accordingly, the present invention also provides a method for reducing influenza A virus infection, or reducing the risk of influenza A virus infection, comprising: administering to a subject in need thereof, a therapeutically effective amount of antibodies according to the present invention, nucleic acids according to the present invention, vectors according to the present invention, cells according to the present invention or pharmaceutical compositions according to the present invention.In addition, the present invention also provides for the use of antibodies according to the present invention, nucleic acids according to the present invention, vectors according to the present invention, cells according to the present invention or pharmaceutical compositions according to the present invention in the preparation of medicaments for the prophylaxis, treatment or attenuation of influenza A virus infection. Diagnostic methods may include contacting antibodies with samples. Such samples may be isolated from the subject, for example, isolated tissue samples taken from, for example, the nasal passages, sinus cavities, salivary glands, lungs, liver, pancreas, kidneys, ears, eyes, placenta, gastrointestinal tract, heart, ovaries, pituitary gland, adrenal gland, thyroid gland, brain, skin, or blood, such as plasma or serum. Diagnostic methods may also include the detection of antigen / antibody complexes, particularly after contact of the antibody with the sample. Such detection steps are usually performed in a benchtop setting, i.e., without contact with the human or animal body. Examples of detection methods are well known to those skilled in the art and include, for example, ELISA (enzyme-linked immunosorbent assay). Influenza A virus infection prophylaxis refers specifically to the prophylactic setting, where the subject is not diagnosed as infected with influenza A virus (no diagnosis has been made or the diagnosis is negative) and / or the subject is not showing symptoms of influenza A virus infection. Influenza A virus infection prophylaxis is particularly useful in subjects at greater risk of severe disease or complications upon infection, such as pregnant women, children (such as children under 59 months), the elderly, individuals with chronic medical conditions (such as chronic heart, lung, kidney, metabolic, neurodevelopmental, liver or hematologic disease) and individuals with immunosuppressive conditions (such as HIV / AIDS, receiving chemotherapy or steroids, or malignancies). In addition, influenza A virus infection prophylaxis is also particularly useful in subjects at greater risk of influenza A virus infection, e.g.due to increased exposure, for example subjects who work or live in public places, especially health workers. In a therapeutic setting, on the other hand, the subject is typically infected with influenza A virus, diagnosed with influenza A virus infection and / or exhibiting symptoms of influenza A virus infection. Of note, the terms treatment and therapy / therapy of influenza A virus infection include (complete) cure as well as attenuation / reduction of influenza A virus infection and / or associated symptoms. Thus, antibodies according to the present invention, nucleic acids according to the present invention, vectors according to the present invention, cells according to the present invention or pharmaceutical compositions according to the present invention can be used for the treatment of influenza. Virus infections in subjects diagnosed with influenza A virus infection or in subjects showing symptoms of influenza A virus infection. Antibodies according to the present invention, nucleic acids according to the present invention, vectors according to the present invention, cells according to the present invention or pharmaceutical compositions according to the present invention may also be used for the prophylaxis and / or treatment of influenza A virus infection in asymptomatic subjects. Such subjects may or may not be diagnosed with influenza A virus infection. In some embodiments, the subject to be treated (e.g., in a prophylactic or therapeutic setting as described above) suffers from an autoimmune or allergic disease; or is at risk for developing an autoimmune or allergic disease. Subjects at risk for developing an autoimmune or allergic disease include those with family members with autoimmune and / or allergic diseases, and those (regularly) exposed to allergens. As demonstrated in the examples of this specification, the antibodies of the present invention exhibit surprisingly low immunogenicity, particularly lower immunogenicity compared to antibodies without the M428L / N434S mutation. Therefore, the antibodies of the present invention may be particularly useful in subjects at risk for a broad immune response. In some embodiments, antibodies according to the present invention, nucleic acids according to the present invention, vectors according to the present invention, cells according to the present invention or pharmaceutical compositions according to the present invention are used for the prophylaxis and / or treatment of influenza A virus infection, wherein the antibodies, nucleic acids, vectors, cells or pharmaceutical compositions are administered up to three months before (possible) influenza A virus infection or up to one month before (possible) influenza A virus infection, such as up to two weeks before (possible) influenza A virus infection or up to one week before (possible) influenza A virus infection.For example, antibodies according to the present invention, nucleic acids according to the present invention, vectors according to the present invention, cells according to the present invention or pharmaceutical compositions according to the present invention are used for the prophylaxis and / or treatment of influenza A virus infection, wherein the antibodies, nucleic acids, vectors, cells or pharmaceutical compositions are administered up to one day before (potential) influenza A virus infection. Such treatment schedules specifically refer to prophylactic settings. In addition, antibodies according to the present invention, nucleic acids according to the present invention, vectors according to the present invention, cells according to the present invention or pharmaceutical compositions according to the present invention may be used for the prophylaxis and / or treatment of influenza A virus infection, wherein the antibodies, nucleic acids, vectors, cells or pharmaceutical compositions are administered up to three months before the first symptoms of influenza A infection occur or up to one month before the first symptoms of influenza A infection occur, such as up to two weeks before the first symptoms of influenza A infection appear or up to one week before the first symptoms of influenza A infection occur.For example, antibodies according to the present invention, nucleic acids according to the present invention, vectors according to the present invention, cells according to the present invention or pharmaceutical compositions according to the present invention are used for the prophylaxis and / or treatment of influenza A virus infection, wherein the antibodies, nucleic acids, vectors, cells or pharmaceutical compositions are administered up to three days or two days before the first symptoms of influenza A infection occur. In general, after the first administration of an antibody according to the present invention, a nucleic acid according to the present invention, a vector according to the present invention, cells according to the present invention or a pharmaceutical composition according to the present invention, one or more subsequent administrations may follow, for example a single dose per day or per every second day for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 1, 15, 16, 17, 18, 19, 20, or 21 days. Following the first administration of the antibody according to the present invention, the nucleic acid according to the present invention, the vector according to the present invention, the cells according to the present invention or the pharmaceutical composition according to the present invention, one or more subsequent administrations may follow, for example a single dose once or twice per week for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 1, 15, 16, 17, 18, 19, 20, or 21 weeks.Following the first administration of the antibody according to the present invention, the nucleic acid according to the present invention, the vector according to the present invention, the cells according to the present invention or the pharmaceutical composition according to the present invention, one or more subsequent administrations may follow, for example a single dose every 2 or 4 weeks for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 1, 15, 16, 17, 18, 19, 20, or 21 weeks. Following the first administration of the antibody according to the present invention, the nucleic acid according to the present invention, the vector according to the present invention, the cells according to the present invention or the pharmaceutical composition according to the present invention, one or more subsequent administrations may follow, for example a single dose every two or four months for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 1, 15, 16, 17, 18, 19, 20, or 21 months.Following the first administration of the antibody according to the present invention, the nucleic acid according to the present invention, the vector according to the present invention, the cells according to the present invention or the pharmaceutical composition according to the present invention, one or more subsequent administrations may follow, for example a single dose once or twice per year for 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 years. In some embodiments, the antibody according to the present invention, the nucleic acid according to the present invention, the vector according to the present invention, the cells according to the present invention or the pharmaceutical composition according to the present invention are administered at a (single) dose of 0.005 to 100 mg / kg body weight or 0.0075 to 50 mg / kg body weight, such as at a (single) dose of 0.01 to 10 mg / kg body weight or at a (single) dose of 0.05 to 5 mg / kg body weight. For example, antibodies according to the present invention, nucleic acids according to the present invention, vectors according to the present invention, cells according to the present invention or pharmaceutical compositions according to the present invention are administered at a (single) dose of 0.1 to mg / kg body weight. Antibodies according to the present invention, nucleic acids according to the present invention, vectors according to the present invention, cells according to the present invention or pharmaceutical compositions according to the present invention may be administered by a number of routes such as oral, intravenous, intramuscular, intra-arterial, intramedullary, intraperitoneal, intrathecal, intraventricular, transdermal, transcutaneous, topical, subcutaneous, intranasal, enteral, sublingual, intravaginal or rectal routes. In some embodiments, the antibodies according to the present invention, the nucleic acids according to the present invention, the vectors according to the present invention, the cells according to the present invention or the pharmaceutical compositions according to the present invention are administered prophylactically, i.e., prior to the diagnosis of influenza A infection. In some embodiments, the antibody of the invention is administered at a dose not exceeding one-half of the dose required for prophylaxis or treatment of influenza A infection with a comparative antibody, which differs from said antibody only in that it does not contain the M428L and N434S mutations in the heavy chain constant region. For example, the dose of the antibody of the invention does not exceed one-third, one-quarter, one-fifth, one-sixth, one-seventh, one-eighth, or one-ninth of the dose required for prophylaxis or treatment of influenza A infection with said comparative antibody. In some embodiments, the antibody of the invention is administered at a dose not exceeding one-tenth of the dose required for prophylaxis or treatment of influenza A infection with said comparative antibody, which differs from said antibody only in that it does not contain the M428L and N434S mutations in the heavy chain constant region.Example 5 of this specification demonstrates that an antibody of the invention comprising the M428L and N434S mutations in the constant region of the heavy chain is effective at significantly lower doses compared to a comparative antibody, which differs from the inventive antibody only in that it does not contain the M428L and N434S mutations in the constant region of the heavy chain. Example 5 also demonstrates that the increased efficacy of the antibody of the invention is independent of circulating antibody levels. Therefore, the antibodies of the present invention can be administered to subjects at immediate risk of influenza A infection. The immediate risk of influenza A infection typically occurs during influenza A epidemics. Influenza A viruses are known to circulate and cause seasonal epidemics of the disease (WHO, Influenza Fact Sheet (Seasonal), November 6, 2018). In temperate regions, seasonal epidemics occur primarily during the winter, whereas in tropical regions, influenza can occur throughout the year, resulting in more irregular outbreaks. For example, in the Northern Hemisphere, the risk of influenza A epidemics is high in November, December, January, February, and March, whereas in the Southern Hemisphere, the risk of influenza A epidemics is high during May, June, July, August, and September. Combination therapy The administration of antibodies according to the present invention, nucleic acids according to the present invention, vectors according to the present invention, cells according to the present invention or pharmaceutical compositions according to the present invention in the methods and uses according to the present invention may be carried out alone or in combination with adjuvants (also referred to as additional active components herein), which may be useful for preventing and / or treating influenza infections. The present invention encompasses the administration of antibodies according to the present invention, nucleic acids according to the present invention, vectors according to the present invention, cells according to the present invention or pharmaceutical compositions according to the present invention, which are administered to a subject before, simultaneously with or after an adjuvant or other therapeutic regimen useful for treating and / or preventing influenza. Such antibodies, nucleic acids, vectors, cells or pharmaceutical compositions, administered in combination with said adjuvants may be administered in the same or different compositions and by the same or different routes of administration. As used herein, expressions such as combination therapy, combination administration, administered in combination and the like are intended to refer to the combined action of drugs (to be administered in combination). For this purpose, combination drugs are typically present at the site of action at the same time and / or at overlapping time windows.It is also possible that the effects of one drug may persist (although the drug itself may no longer be present) while the other drug is being administered, allowing the effects of the two drugs to interact. However, drugs that are given long before the other drug (e.g., more than one, two, three, or more months or a year), such that they are no longer present (or their effects are not ongoing) when the other drug is administered, are not usually considered to be given in combination. For example, influenza drugs given in different influenza seasons are not usually given in combination.” Such therapeutic regimens or other adjuvants may include, for example, antivirals. Antivirals (or antiviral agents or antiviral drugs) refer to a class of medications used specifically to treat viral infections. Like antibiotics for bacteria, antivirals can be broad-spectrum antivirals, which are effective against a wide range of viruses, or specific antivirals, which are used for specific viruses. Unlike most antibiotics, antiviral drugs do not typically destroy their target pathogens; instead, they typically inhibit their growth. Thus, in another aspect of the present invention the antibody, or antigen-binding fragment thereof, according to the present invention, the nucleic acid according to the present invention, the vector according to the present invention, the cells according to the present invention or the pharmaceutical composition according to the present invention is administered in combination with (before, simultaneously or after) an antiviral for (medical) use as described herein. In general, antivirals can be broad-spectrum antivirals (useful against influenza viruses and other viruses) or influenza-specific antivirals. In some embodiments, antivirals are not antibodies. For example, antivirals can be small molecule drugs. Examples of small molecule antivirals useful in the prophylaxis and / or treatment of influenza are described in: Wu X, Wu X, Sun Q, et al. Progress of small molecule inhibitors in the development of anti-influenza virus agents. Theranostics. 2017;7(4):826-845. As described in Wu et al., 2017, the skilled artisan is familiar with various antivirals useful in the prophylaxis and / or treatment of influenza. Further antivirals useful in influenza are described in Davidson S. Treating Influenza Infection, From Now and Into the Future. Front Immunol. 2018;9:1946; and in: Koszalka P, Tilmanis D, Hurt AC. Influenza antivirals currently in late-phase clinical trial. Influenza Other Respir Viruses. 2017; 11(3):240-24 6. Antivirals useful in the prophylaxis and / or treatment of influenza include (i) agents that target functional proteins of the influenza virus itself and (ii) agents that target host cells, e.g., epithelium. Host cell-targeting agents include the thiazolide class of broad-spectrum antivirals, sialidase fusion proteins, type III interferons, Bcl-2 (B-cell lymphoma 2) inhibitors, protease inhibitors, V-ATPase inhibitors, and antioxidants. Examples of the thiazolide class of broad-spectrum antivirals include nitazoxanide (NTZ), which is rapidly deacetylated in the blood to its active metabolic form tizoxanide (TIZ), and second-generation thiazolide compounds, structurally related to NTZ, such as RM5061. Fludase (DAS181) is an example of a sialidase fusion protein. Type III IFNs include, for example, IFNλ. Examples of non-restrictive Bcl-2 inhibitors include ABT-737, ABT263, ABT-199, WEHI-539, and A-1331852 (Davidson S. Treating Influenza Infection, From Now and Into the Future. Front Immunol. 2018; 9:1946). Examples of protease inhibitors include nafamostat, leupeptin, epsilon-aminocapronic acid, camostat, and aprotinin. V-ATPase inhibitors include norakinR, parkopanR, antiparkinR, and akinetonR.An example of an antioxidant is alpha-tocopherol. In some embodiments, antivirals are agents that target functional proteins of the influenza virus itself. For example, antivirals may target functional proteins of the influenza virus, which are not hemagglutinin. In general, antivirals that target functional proteins of the influenza virus include entry inhibitors, hemagglutinin inhibitors, neuraminidase inhibitors, influenza polymerase inhibitors (RNA-dependent RNA polymerase (RdRp) inhibitors), nucleocapsid protein inhibitors, M2 ion channel inhibitors, and arbidol hydrochloride. Non-limiting examples of entry inhibitors include triterpenoid derivatives, such as glycyrrhizin and glycyrrhetinic acid; saponins; uralsaponin MY (such as uralsaponin M); dextran sulfate (DS); silymarin; curcumin; and lysosomotropic agents, such as Concanamycin A, Bafilomycin A1, and Chloroquine. Non-limiting examples of hemagglutinin inhibitors include BMY-27709; stachyflin; natural products, such as Gossypol, Rutin, Quercetin, Xylopine, and Theaflavin; trivalent glycopeptide mimetics, such as compound 1 described in Wu X, Wu X, Sun Q, et al. Progress of small molecular inhibitors in the development of anti-influenza virus agents. Theranostics. 2017;7(4):826-845; podocarpic acid derivatives, such as compound 2 described in Wu X, Wu X, Sun Q, et al. Progress of small molecular inhibitors in the development of anti-influenza virus agents. Theranostics. 2017;7(4):826-845; pentacyclic triterpenoid natural products, such as compound 3 described in Wu X, Wu X, Sun Q, et al. Progress of small molecular inhibitors in the development of anti-influenza virus agents. Theranostics. 2017;7(4):826—845; and prenylated indole diketopiperazine alkaloids, such as Neoechinulin B. Examples of non-limiting nucleocapsid protein inhibitors include nucleozin, Cycloheximide, Naproxen and Ingavirin.Non-limiting examples of M2 ion channel blockers include the approved M2 blockers Amantadine and Rimantadine and their derivatives; as well as non-adamantane derivatives, such as Spermine, Spermidine, Spiropiperidine and pinanamine derivatives. In some embodiments, the antiviral is selected from a neuraminidase (NA) inhibitor and an influenza polymerase (RNA-dependent RNA polymerase (RdRp) inhibitor). Examples of non-limiting neuraminidase (NA) inhibitors include zanamivir; oseltamivir; peramivir; laninamivir; derivatives thereof such as compounds 4 - 10 described in Wu X, Wu X, Sun Q, et al. Progress of small molecular inhibitors in the development of anti-influenza virus agents. Theranostics. 2017;7(4):826-845, and zanamivir dimer conjugates (e.g., as described in Wu X, Wu X, Sun Q, et al. Progress of small molecule inhibitors in the anti-influenza virus agents. Theranostics. development of 2017;7(4):82661 845); benzoic acid derivatives (e.g., as described in Wu X, Wu X, Sun Q, et al. Progress of small molecular inhibitors in the development of anti-influenza virus agents. Theranostics. 2017;7(4):826-845; such as compounds 11 - 14); pyrrolidine derivatives (e.g., as described in Wu X, Wu X, Sun Q, et al. Progress of small molecular inhibitors in the development of anti-influenza virus agents. Theranostics. 2017;7(4):826-845; such as compounds 15 - 18); ginkgetin-sialic acid conjugates; flavanones and flavonoids isoscutellarein and their derivatives (e.g., as described in Wu X, Wu X, Sun Q, et al. Progress of small molecular inhibitors in the development of anti-influenza virus agents. Theranostics. 2017;7(4):826-845); AV5080; and N-substituted oseltamivir analogs (e.g., as described in Wu X, Wu X, Sun Q, et al. Progress of small molecular inhibitors in the development of anti-influenza virus agents. Theranostics. 2017;7(4):826-845).Non-limiting examples of influenza polymerase (RNA-dependent RNA polymerase (RdRp)) inhibitors include RdRp-disrupting compounds, as described in Wu X, Wu X, Sun Q, et al. Progress of small molecule inhibitors in the development of anti-influenza virus agents. Theranostics.2017;7(4):826-845; PB2 cap-binding inhibitors, such as JNJ63623872 (VX-787); cap-dependent endonuclease inhibitors, such as baloxavir marboxil (S-033188); PA endonuclease inhibitors, such as AL-794, EGCG and its aliphatic analogs, N-hydroxamic acid and N-hydroxymide, flutimide and its aromatic analogs, tetramic acid derivatives, L-742,001, ANA-0, polyphenolic catechins, phenethyl-phenylphthalimid analogs, macrocyclic bisbibenzyls, pyrimidinols, fullerenes, hydroxyquinolinones, hydroxypyridinones, hydroxypyridazinones, trihydroxyphenyl-containing compounds, 2-hydroxybenzamides, hydroxypyrimidinones, diketoacids and their bioisosteric compounds, and perazpyridoxycarbazone (Endo-1); and nucleoside and nucleotide base analog inhibitors, such as ribavirin, favipiravir (T-705), 2'-Deoxy-2'-fluoroguanosine (2'-FdG), 2'-substituted carbanucleoside analogs, 6-methyl-7-substituted purine nucleoside analogs, and 2'-deoxy-2'-fluorocytidine (2'-FdC).For example, antivirals can be zanamivir, oseltamivir or bolosavir. Thus, the pharmaceutical composition according to the present invention may comprise one or more additional active components. The antibody according to the present invention may be present in the same pharmaceutical composition as the additional active component (adjuvant). Alternatively, the antibody according to the present invention and the additional active component (adjuvant) may be comprised in different pharmaceutical compositions (e.g., not in the same composition). Thus, if more than one additional active component (adjuvant) is considered, each additional active component (adjuvant) and the antibody, or antigen-binding fragment, according to the present invention may comprise a different pharmaceutical composition. Such different pharmaceutical compositions may be administered either in combination / simultaneously or at separate times and / or by separate routes of administration. The antibodies according to the present invention and additional active components (adjuvants) may provide additive or synergistic therapeutic effects. The term synergy is used to describe the combined effect of two or more active substances that is greater than the sum of the individual effects of each active substance. Thus, if the combined effect of two or more substances results in “synergistic inhibition” of an activity or process, it is intended that the inhibition of that activity or process is greater than the sum of the inhibitory effects of the individual active substances. The term synergistic therapeutic effect refers to a therapeutic effect observed with a combination of two or more therapies where the therapeutic effect (as measured by one of a number of parameters) is greater than the sum of the individual therapeutic effects observed with each individual therapy. Therefore, the present invention also provides a combination of (i) the antibody of the invention as described herein, and (ii) the antiviral agent as described above. Short Description of Image The following is a brief explanation of the accompanying drawings. These drawings are intended to illustrate the present invention in greater detail. However, they are not intended to limit the subject matter of the invention in any way. Figure 1 shows for Example 2 the plasma concentrations of human antibodies FluAB_MLNS (open squares) and FluAB_wt (comparative antibody; filled circles) in macaque plasma samples assessed via ELISA up to day 56. Figure 2 shows for Example 3 the plasma concentrations of FluAB_MLNS (animals C90142, C90190) measured using either an anti-CH2 antibody ELISA to measure total human mAb or an HA antigen binding ELISA to determine mAb functionality. The graph shows a linear regression between total human mAb quantification and HA binding for each animal at selected time points (days 1, 21, 56, 86, and 113). Figure 3 shows for Example 4 (A) the concentrations of human antibodies FluAB_MLNS and FluAB_wt in nasal swabs measured using ELISA and normalized to urea content; and (B) Biodistribution of human antibodies FluAB_MLNS and FluAB_wt, expressed as % of normalized urea concentration in nasal swabs over plasma concentration. The individual animal IDs and the human antibody variants inoculated (FluAB_MLNS or FluAB_wt) are shown below. Figure 4 shows for Example 5 the cumulative body weight change over time in Tg32 mice treated with FluAB_wt (panels B, D, circles), FluAB_MLNS (panels C, E, squares) at 1 mg / kg (panels B, C, gray symbols) and 0.3 mg / kg (panels D, E, light gray symbols) or untreated (panel A, triangles); all mice were infected intranasally with PR8 virus. Individual animals are shown; Thick black lines represent the trend in mean BW±SD. Number of individuals per group is indicated. * p< 0.05, ** p< 0.01, *** p< 0.001 vs control alone (A), ° p< 0.05, °° p< 0.01, all vs MEDI8852 relative time points, 2-way ANOVA with Bonferroni multiple test correction. Figure 5 shows an Example 5 % survival comparison between the 1 mg / kg dose (left panel) and the 0.3 mg / kg dose (right panel) in infected male Tg32 mice treated with nothing (dotted line), FluAB_wt, or FluAB_MLNS. ** p<0.01 vs untreated mice (CTR) and FluAB_MLNS 0.3 mg / kg; °°° p<0.001 vs FluAB_wt, log-rank analysis, Mantel-Cox method. Figure 6 shows for Example 5 the circulating levels of injected antibodies. Individual levels (pg / ml) of circulating FluAB_wt (circles) and FluAB_MLNS (squares) measured in mouse serum, immediately before (Day 0) and 6 days after infection are shown. Bars represent mean ± SD. Figure 7 shows for Example 6 the plate schematic used in the in vitro neutralization test. Figure 8 shows for Example 6 the neutralization activity of FluAB_MLNS and Oseltamivir alone in H1N1 (A, C) and H3N2 (B, D) virus infections. Figure 9 shows for Example 6 the combined neutralization activity of FluAB_MLNS and Oseltamivir on H1(A) and H3(B) virus infections. The data indicate the fraction inhibited by FluAB_MLNS alone and in combination with heteromolar concentrations of Oseltamivir on both H1N1(A) and H3N2(B) virus infections of MDCK cells. Data are represented as the mean ± SD of triplicate values, each replicate obtained in three independent culture plates. Figure 10 shows for Example 6 the median effect plot of the combination of FluAB_MLNS and Oseltamivir. Both compounds were serially diluted at the indicated constant ratios and added to MDCK cells infected with H1(A) and H3(B) virus strains. The values ​​obtained from the selected combinations at non-constant ratios (NCR) are also shown. Figure 11 shows for Example 6 the combination index of FluAB_MLNS and Oseltamivir for H1N1 virus infection. The dots represent actual experimental points at the indicated constant ratio with the denoted accumulated drug concentration. The dashed curve shows the predicted combination index across the full effect range. Figure 12 shows for Example 6 the combination index of FluAB_MLNS and Oseltamivir for H3N2 virus infection. The dots represent actual experimental points at the indicated constant ratios with the denoted accumulated drug concentrations. The dashed curve shows the predicted combination index across the full effect range. Figure 13 shows Example 6 isobolograms of the FluAB_MLNS-Oseltamivir combination for H1N1 virus infection. The dots indicate the IC50, IC75 and IC90 values ​​at different constant ratio combinations of FluAB_MLNS-Oseltamivir. For each experimental point, the accumulated concentration is shown. Figure 14 shows for Example 6 the isobologram of the FluAB_MLNS-Oseltamivir combination for H3N2 virus infection. The dots indicate the IC50, IC75 and IC90 values ​​at different constant ratio combinations of FluAB_MLNS-Oseltamivir. For each experimental point, the accumulated concentration is shown. Figure 15 shows for Example 6 the neutralization activity FluAB_MLNS and Zanamivir alone in H1N1 (A, C) and H3N2 (B, D) virus infections. Figure 16 shows Example 6 of the combined neutralization activity of FluAB_MLNS and Zanamivir on H1(A) and H3(B) virus infections. The data show the fraction inhibited by FluAB_MLNS alone and in combination with heteromolar concentrations of Zanamivir on both H1N1(A) and H3N2(B) virus infections of MDCK cells. Data are represented as the mean ± SD of triplicate values, each replicate obtained in three independent culture plates. Figure 17 shows for Example 6 the median effect plot of the combination of FluAB_MLNS and Zanamivir. Both compounds were serially diluted at the indicated constant ratios and added to MDCK cells infected with H1(A) and H3(B) virus strains. The values ​​obtained from the selected combinations at non-constant ratios (NCR) are also shown. Figure 18 shows for Example 6 the combination index of FluAB_MLNS and Zanamivir for H1N1 virus infection. The dots represent actual experimental points at the indicated constant ratios with the denoted accumulated drug concentrations. The dashed curve shows the predicted combination index across the full effect range. Figure 19 shows for Example 6 the combination index of FluAB_MLNS and Zanamivir for H3N2 virus infection. The dots represent actual experimental points at the indicated constant ratios with the denoted accumulated drug concentrations. The dashed curve shows the predicted combination index across the full effect range. Figure 20 shows Example 6 isobolograms of the FluAB_MLNS-Zanamivir combination for H1N1 virus infection. The dots indicate the IC50, IC75, and IC90 values ​​at different constant ratio combinations of FluAB_MLNS-Zanamivir. For each experimental point, the accumulated concentration is shown. Figure 21 shows Example 6 isobolograms of the FluAB_MLNS-Zanamivir combination for H3N2 virus infection. The dots indicate the IC50, IC75 and IC90 values ​​at different constant ratio combinations of FluAB_MLNS-Zanamivir. For each experimental point, the accumulated concentration is shown. Figure 22 shows for Example 6 the neutralization activity of FluAB_MLNS and Baloxavir alone in H1N1 (A, C) and H3N2 (B, D) virus infections. Figure 23 shows Example 6 of the combined neutralization activity of FluAB_MLNS and Baloxavir on H1(A) and H3(B) virus infections. The data show the fraction inhibited by FluAB_MLNS alone and in combination with heteromolar concentrations of Baloxavir on both H1N1(A) and H3N2(B) virus infections of MDCK cells. Data are represented as the mean ± SD of triplicate values, each replicate obtained in three independent culture plates. Figure 24 shows for Example 6 the median effect plot of the combination of FluAB_MLNS and Baloxavir. Both compounds were serially diluted at the indicated constant ratios and added to MDCK cells infected with H1(A) and H3(B) virus strains. The values ​​obtained from the selected combinations at non-constant ratios (NCR) are also plotted. Figure 25 shows for Example 6 the combination index of FluAB_MLNS and Baloxavir. The dots represent the actual experimental points at the indicated constant ratios with the accumulated drug concentrations denoted. The dashed curve shows the predicted combination index across the full effect range. Figure 26 shows for Example 6 the isobologram of the FluAB_MLNS-Baloxavir combination. The dots indicate the IC50, IC75 and IC90 values ​​at different constant ratio combinations of FluAB_MLNS-Baloxavir. For each experimental point, the accumulated concentration is shown.Figure 27 shows for Example 7 the binding of human FcRn in solution to immobilized FluAB_MLNS (grey line) or FluAB_wt (black line) as measured by Octet at pH=6.0 (A) or pH=7.4 (B). The 0 s time point represents the switch from the baseline buffer to the buffer containing human FcRn. The 420 s time point (gray dashed vertical line) represents the switch to empty buffer at the corresponding pH. Association and dissociation profiles were measured in real time using Octet RED96 (ForteBio). Figure 28 shows for Example 9 the ADA response levels measured by ELISA for the detection of mouse anti-drug IgG (A; bars represent the mean ± SD of treatment groups); and the correlation analysis (B) between circulating human IgG levels measured 14 days after iv injection (X-axis) and the ADA signal present at the same time point (Y-axis). Non-parametric Spearman correlation coefficients are shown for significant values. Figure 29 shows for Example 10 the level of ADA response after subcutaneous (s.c.) injection of FluAB_MLNS or FluAB_wt. Data are represented as the ADA signal value (OD 450 nm) detected in each individual serum obtained three weeks after s.c. injection (n=5 / group), pre-diluted in PBS 1:25 and subsequently serially diluted 5-fold. Complete Description of the Invention Examples Following are specific examples illustrating various embodiments and aspects of the present invention. However, the present invention should not be limited in scope by the specific embodiments described herein. The following fabrications and examples are provided to enable those skilled in the art to more clearly understand and practice the present invention. The present invention, however, is not limited in scope by the exemplary embodiments, which are intended to illustrate only a single aspect of the invention, and functionally equivalent methods are within the scope of the invention. Indeed, various modifications of the invention other than those described herein will be apparent to those skilled in the art from the foregoing description, the accompanying drawings, and the examples below. All such modifications are within the scope of the appended claims. Example 1: safety and tolerability of antibodies according to the present invention in cynomolgus monkeys An antibody according to the present invention, comprising (i) a CDR sequence as set forth in SEQ ID NO. 1 - 6 and (ii) two mutations M428L and N434S in the heavy chain constant region, is designed and manufactured. More specifically, the antibody comprises (i) a heavy chain variable region (VH) sequence as set forth in SEQ ID NO: 7 and a light chain variable region (VL) sequence as set forth in SEQ ID NO: 8; and (ii) two mutations M428L and N434S in the heavy chain constant region. More specifically, the antibody comprises a heavy chain having the amino acid sequence as set forth in SEQ ID NO: 9 and a light chain having the amino acid sequence as set forth in SEQ ID NO: 10. This antibody is referred to herein as FluAB_MLNS. For comparison, the FluAB_wt antibody used, differs from the FluAB_MLNS antibody only in that it does not contain the two mutations M428L and N434S in the constant region of the heavy chain. Thus, the comparative antibody “FluAB_wt” consists of a heavy chain having the amino acid sequence as specified in SEQ ID NO: 11 and a light chain having the amino acid sequence as specified in SEQ ID NO: 10. A single intravenous infusion of 5 mg / kg of FluAB_MLNS or FluAB_wt in a volume of 2.5 ml / kg was administered as a 60-minute intravenous infusion to three female cynomolgus macaques (Macaca fascicularis) per test group. Blood or urine for clinical chemistry and hematology analysis was collected before dosing and on days 7 and 21 post-dose. Following administration of FluAB_MLNS or FluAB_wt at 5 mg / kg via a 60-minute intravenous infusion, female cynomolgus macaques were closely monitored for health and body weight, and blood and urine samples were collected regularly. No adverse events—other than bruising 24 hours after administration and erythroderma 3 days post-dose at the inoculation site in some animals—were observed following intravenous antibody inoculation. All animals were generally healthy, exhibited normal food consumption, and had overall positive weight gain throughout the study. Clinical chemistry, hematology, and urinalysis parameters were normal at 7 or 21 days post-dose, compared with pre-dose samples. In summary, a single intravenous infusion of FluAB_MLNS or FluAB_wt into cynomolgus macaques did not cause adverse effects and was generally well tolerated. Example 2: Determination of plasma concentration and pharmacokinetics This experiment aims to determine the concentration, determine the half-life, and compare the pharmacokinetics of the antibody according to the present invention FluAB_MLNS compared to the comparative antibody FluAB_wt in plasma after a single intravenous injection. Prior to dosing, animals tested negative for influenza-specific antibodies using a dot immunobinding assay. Seropositive animals were excluded from the study because pre-existing immunity could interfere with this assay. Additionally, animals that developed an antidrug antibody response (ADA) were excluded. A single intravenous infusion of 5 mg / kg of FluAB_MLNS or FluAB_wt in a volume of 2.5 ml / kg was administered as a 60-minute intravenous infusion to three female monkeys per test group. Blood was collected in tubes containing a pre-dose of K2EDTA and processed to plasma for pharmacokinetic testing after approximately 1, 6, 24, 96, 168, 504, 840, and 1344 hours (h) post-dose. Plasma antibody concentrations were determined in vitro using an ELISA assay. Briefly, IAV-HA antigen (Influenza A Virus H1N1 A / California / 07 / 2009 Hemagglutinin Protein Antigen (with His Tag); Sino Biologicals) was diluted to 2 pg / ml in PBS and 25 pl were added to the wells of a 96-well flat-bottom ELISA plate for coating overnight at 4°C. After coating, the plate was washed twice with 0.5x PBS supplemented with 0.05% Tween20 (wash solution) using an automated ELISA washer. Then the plate was blocked with 100 pl / well of PBS supplemented with 1% BSA (blocking solution) for 1 hour at room temperature (RT) and washed twice. Plasma samples were centrifuged at 10,000 g for 10 min at 4°C and then diluted (1:10 and then 1:30) to a final dilution of 1:300 in blocking solution in 96-well cell culture plates.The minimum dilution (1:300) of macaque plasma used for quantification was tested and adjusted to ensure negligible matrix effects. Samples were then diluted 1:2 in triplicate for a total of 12 dilutions. Standards for each antibody to be tested were prepared similarly by diluting the antibody 1:300 to 1 pg / ml in pooled pre-inoculation plasma from all test animals, mimicking the test sample matrix. Standards were then diluted 1:3 in blocking solution in triplicate for a total of 12 dilutions. Twenty-five pl of the prepared samples or standards were added to hemagglutinin (HA)-coated wells and incubated for 1 hour at RT. After four washes, 25 μl of goat anti-human IgG HRP conjugate (AffiniPure F(ab')2Fragment, Fcy Fragment-Specific; Jackson ImmunoResearch) diluted in blocking solution 1:5'000 (final concentration 0.16 μg / ml) was added per well for detection and incubated at RT for 1 h.After four washes, the plates were developed by adding 40 μl per well of SureBlue TMB Substrate (Bioconcept). After 7–20 min of incubation at RT, when the color reaction reached a plateau (max OD ~3.8), 40 μl of 1% HCl was added per well to stop the reaction and absorbance was measured at 450 nm using a spectrophotometer. To determine antibody concentrations in cynomolgus plasma, OD values ​​from ELISA data were plotted against concentration in Gen5 software (BioTek). A nonlinear curve fit was applied using a variable slope model, four parameters and the equation: Y=(AD) / (1+(X / C)ΛB)+D). OD values ​​from sample dilutions that fell within the predictable test range of the standard curve as determined in the setup experiment by quality control samples in the upper, middle, or lower range of the curve were interpolated to quantify the sample. Plasma antibody concentrations were then determined considering the final sample dilutions. If more than one sample dilution value fell within the linear range of the standard curve, the average of these values ​​was used. Pharmacokinetic (PK) data were analyzed using the WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM (8.1.0.3530 Core Version, Phoenix software, Certara) with the following settings: Model: Plasma Data, Constant Infusion; Number of non-missing observations: 8; Steady-state Tau interval: 1.00; Dose time: 0.00; Dose number: 5.00 mg / kg; Infusion duration: 0.04 days; Calculation method: Linear trapezoidal with linear interpolation; Weighting for lambda_z calculation: Uniform weighting; Lambda_z method: Find the best fit for lambda_z, Log regression. Graphs and statistical analysis (linear regression or outlier analysis) were performed using Prism 7.0 software (GraphPad, La Jolla, CA, USA). Outlier analysis was performed using the ROUT method (Q=1%), with the potential to find a number of outliers in both directions. The results are shown in Figure 1. Analysis of cynomolgus plasma samples taken up to 56 days post-inoculation showed that the antibody according to the present invention FluAB_MLNS had a prolonged in-vivo half-life compared to the comparative antibody FluAB_wt (Fig. 1). Using noncompartmental analysis with WinNonLin, the T1 / 2 was estimated to be 19.5 days for the antibody according to the present invention FluAB_MLNS, while the T1 / 2 was estimated to be 11.6 days for the comparative antibody FluAB_wt. The lower limit of quantification was 300 ng / ml. In summary, the antibody according to the present invention FluAB_MLNS has an extended in-vivo half-life compared to the comparative antibody FluAB_wt at least up to day 56 post-inoculation. Example 3: Long-term stability in vivo To test the in-vivo stability and functionality of the antigen binding of the antibody according to the present invention FluAB_MLNS over time, pharmacokinetic measurements (as described in Example 2) of the group receiving the antibody according to the present invention FluAB_MLNS were extended to days 86 and 113 post-inoculation. On days 1, 21, 56, 86, and 113 post-inoculation, functional FluAB_MLNS were quantified using a hemagglutinin (HA) binding ELISA as described in Example 2. Furthermore, total human antibodies in macaque plasma were quantified using a specific anti-CH2 ELISA, using a capture mAb that specifically binds the human CH2 region but not macaque Abs. To quantify total human IgG and thus quantify total inoculated human antibodies in macaque plasma, a capture ELISA with a mouse anti-CH2 domain specific for human IgG (clone R10Z8E9; Thermo Scientific) was used. It was verified that this mAb does not cross-react with macaque IgG. For coating of 96-well flat-bottom ELISA plates, mouse anti-human IgG CH2 was added in PBS at 0.5 pg / ml and incubated overnight at 4°C. Then, the plates were washed and 100 pl / well blocking solution with 5% BSA was added for 1 hour at RT. The antibody standard according to the present invention FluAB_MLNS was prepared by diluting FluAB_MLNS to 1 ng / ml in blocking solution.The standards were then diluted 1:1.5 in duplicate in blocking solution for a total of 12 dilutions. Cynomolgus plasma samples were centrifuged at 10,000 g for 10 min at 4°C and diluted in duplicate to a final 1:1,000, 1:5,000, or 1:15,000 dilution in blocking solution. After washing the plates, 25 μl of sample or standard was added to the ELISA plate and incubated for 1 h at RT. After three washes, 25 μl of goat anti-human IgG HRP (AffiniPure F(ab')2Fragment, Fcy Fragment-Specific; Jackson ImmunoResearch) at 0.04 pg / ml was added to the blocking solution with 1% BSA for detection and incubated at RT for 45 min. After three washes, the plates were developed by adding 40 μl per well of SureBlue TMB Substrate (Bioconcept). After 20 min of incubation at RT, 40 μl of 1% HCl was added to stop the reaction, and absorbance was measured at 450 nm. The results are shown in Figure 2. Both quantifications yielded similar concentrations of human antibodies in cynomolgus plasma (Fig. 2). Additional analysis via linear regression showed that the relationship between quantification via HA binding and total anti-CH2 quantification followed a linear pattern for all selected time points. Consequently, the total amount of FluAB_MLNS present in plasma is functional in binding the hemagglutinin (HA) stem region of influenza A virus (IAV), also after 86 and 113 days in vivo. In summary, the antibody according to the present invention FluAB_MLNS showed functional antigen binding and thus good long-term stability in vivo up to day 113 post-inoculation during the extension study. Example 4: Antibody concentration in nasal swabs and biodistribution To determine the biodistribution of the antibody according to the present invention FluAB_MLNS and the comparative antibody FluAB_wt among nasal mucus relative to plasma, antibody concentrations were determined in nasal swabs. For this purpose, nasal swabs from macaques described in Example 2 were collected 24, 504, and 1344 hours after administration of the antibody according to the present invention FluAB_MLNS or the comparative antibody FluAB_wt. The concentrations of the antibody FluAB_MLNS and FluAB_wt in nasal swabs were determined essentially as described in Example 2 for determination in plasma with the following minor adaptations: (a) ELISA plates were blocked for 2 hours at RT; (b) Nasal swab samples were diluted starting at 1:2 with 1% BSA in PBS and then serially diluted in 1:2 steps for a total of 8 dilution points; (c) nasal swab medium (RT MINI Viral Transport Medium; Copan) was used as the assay matrix control. To eliminate differences during the swabbing procedure or in the amount of nasal secretions present in each animal and at different time points (days 1, 21, and 56), nasal swab results were normalized to urea content. Urea freely diffuses throughout the blood, being present in equal amounts in all plasma or swab samples (Lim et al., 2017, Antimicrob Agents Chemother 61(8):e00279-17). For this purpose, urea nitrogen (BUN) was measured quantitatively using the “Urea Nitrogen (BUN) Colorimetric Detection Kit” (Invitrogen), following the manufacturer's procedure. Briefly, samples were diluted 1:3 in PBS and mixed with kit reagents A and B and incubated at room temperature for 30 minutes. The colored products of the redox reaction were read at 450 nm using a 96-well microplate reader. Quantification was performed by comparing the samples with BUN standards, which were provided with the kit and treated similarly. The results are shown in Figure 3. The normalized antibody counts in nasal swabs decreased over time (Fig. 3A). Determining biodistribution by comparing nasal to plasma concentrations revealed no difference between the antibody according to the present invention FluAB_MLNS and the comparative antibody FluAB_wt (Fig. 3B), indicating that the MLNSFc mutation, while extending the half-life of FluAB_MLNS in plasma, does not improve the biodistribution of the antibody into nasal mucus. In summary, nasal swab samples did not reveal significant differences in biodistribution between nasal mucus and plasma among the three mAb variants. Example 5: Prophylactic activity of FluAB MLNS antibody in PR8-infected Tg32 mice Further, the prophylactic activity of the antibody according to the present invention FluAB_MLNS compared to the antibody FluAB_wt was determined in a H1N1 murine model of lethal influenza A infection. To evaluate prophylactic efficacy, 9- to 14-week-old Tg FcRn- / hFcRn line 32 mice (C57B6 background) were injected intravenously (iv) (via the tail vein) with 5 ml / kg of a solution containing the antibody according to the present invention FluAB_MLNS or the comparative antibody FluAB_wt at doses ranging from 0.3 to 1 mg / kg. Twenty-four hours after the iv injection, blood was drawn from the tail vein of the mice to determine serum antibody levels before infection. Bleeding was also repeated on days 6 and 13 post-infection (p.i.). Antibody-injected and untreated mice were anesthetized (isoflurane, 4% in O2, 0.3 L / min) and challenged intranasally (deeply) by slowly instilling in both nostrils 50 pl (25 pl / each) of PBS containing 5 fifty percent mouse lethal doses (5 MLD50, equivalent to 1200 TCID50 / mouse) of influenza A virus (H1N1, A / Puerto Rico / 8 / 34, as described in Cottey, R., Rowe, CA, and Bender, BS (2001).Influenza virus. Curr Protoc Immunol Chapter 19, Unit 19.11-19.11.32). Each mouse was held upright with its head tilted slightly back for approximately 1 minute to reduce the possibility of inoculum dripping from the nostrils. After the procedure and upon the onset of the correct reflex, the animal was returned to its home cage. Mice were monitored daily for weight loss and disease symptoms until day 14 p.i. and euthanized if they lost more than 20% of their initial body weight (where 0% was set on the day of infection) or reached a morbidity score of 4. Table 1 details the morbidity scores applied: Table 1 - Morbidity Score of PR8-infected mice Morbidity Score Clinical signs 1 Healthy 2 Consistent ruffling of neck hair 3 Piloerection, possible deeper breathing, less alert 4 Labored breathing, tremors and lethargy 5 Abnormal gait, reduced mobility, emaciation, ear-tail cyanosis 6 Death All animals were eventually sacrificed to collect serum and lungs. Serum Making: Approximately 0.05 ml of blood was collected into a gel-containing tube and allowed to stand for 30 minutes at RT. The tube was spun for 5 minutes at 5500 rpm (3200 x g), the serum was transferred to a new tube and stored at -20 °C until use. Two independent experiments were conducted, according to the following design: Table 2 - Experimental Design Study 1: Group N Animal IV Treatment mAb Dose 1 4 - 5 2 8 FluAB_wt 1 mg / kg 3 4 FluAB_wt 0.3 mg / kg 4 8 FluAB_MLNS 1 mg / kg 5 4 FluAB_MLNS 0.3 mg / kg Table 1 - Experimental Design Study 2: Group N Animal IV Treatment mAb Dose 1 9 2 10 FluAB_wt 0.3 mg / kg 3 6 FluAB_MLNS 0.3 mg / kg ELISA quantification of circulating mAbs: 15 Sera were assessed for circulating antibody levels on days 0 and 6. Briefly, half-area ELISA plates were coated overnight at 4°C with recombinant hemagglutinin (HA) from the H1N1 strain A / California / 07 / 09 (2 g / ml, in 20 μl PBS, 25 μl / well). After blocking (PBS / 1% BSA, 100 pl / well, 1 h RT) and 2 washes (220 μl / well) with ELISA wash solution (PBST), both serum dilutions (initial dilution 1:150 for 1 mg / kg, 1:50 for 0.3 mg / kg) and antibody standards (FluAB_MLNS and FluAB_wt, 0.1 g / ml) 25 were added (25 μl / well) in duplicate and serially diluted (1:2 times 10 points for serum dilution, 1:3 times 8 points for antibody standard). After 1.5 h RT incubation, the plates were washed 4 times with PBST and further incubated 1.5 hours at RT with HRP-labeled anti-human secondary antibody (0.16 μg / ml, 25 μl / well). After 4 washes with PBST, the plates were treated with substrate solution (25 μl / well), developed for 14 minutes, and blocked with 1% HCl (v / v, 25 μl / well). The plates were finally read at 450 nm with a spectrophotometer for signal quantification. Concentration values ​​were calculated using a non-linear regression model (variable slope model, four parameters, GraphPad Prism) log (agonist) versus response. Data analysis: Data were plotted and analyzed using GraphPad Prism software version 8.0 for Macintosh, GraphPad Software, La Jolla, California, USA, www.graphpad.com. Continuous variables were assessed for statistically significant differences (p<0.05, 95% confidence interval) using ordinary 2-way ANOVA corrected by Bonferroni's multiple comparisons test. Survival data were compared using log-rank analysis with the Mantel-Cox method (p<0.05 was considered statistically significant). Data from the two independent experiments described above were pooled. Results: Prophylactic activity was tested by intravenous administration of FluAB_MLNS and FluAB_MLNS (1 and 0.3 mg / kg) to Tg32 mice one day before H1N1 PR8 virus challenge via intranasal infection. The results are shown in Figures 4–6. As depicted in Figure 4, mice treated with 1 mg / kg (panel D) or 0.3 mg / kg (panel E) of FluAB_MLNS showed lower body weight loss, compared to untreated (panel A) and FluAB_wt-injected (panels B and C) mice. The better protective activity of FluAB_MLNS compared to FluAB_wt was confirmed in the survival analysis shown in Figure 5. The difference in efficacy between FluAB_MLNS and FluAB_wt did not correlate with circulating antibody levels in serum, measured 1 and 7 days after IV antibody administration (Figure 6). Of note, no detectable circulating antibody levels were measured 14 days after injection (not shown). In summary, FluAB_MLNS demonstrated, in Tg32 mice, a superior protective capacity against intranasal H1N1 PR8 virus challenge compared to the comparative antibody FluAB_wt. The efficacy was independent of circulating antibody levels. These data suggest that the enhanced interaction of FluAB_MLNS with hFcRn expressed by Tg32 mice also mediates in vivo effects unrelated to the extended antibody half-life, such as increased efficacy related to protective activity. Example 6: Combination of FluAB MLNS antibody with various antivirals Drug combinations offer a clear opportunity to enhance potency while reducing the likelihood of selecting for resistance. Furthermore, additive or synergistic effects are thought to result in dose-sparing approaches. Currently FDA-approved influenza drugs include the neuraminidase inhibitors oseltamivir and zanamivir, as well as the recently approved baloxavir marboxil, which belongs to the class of endonuclease inhibitors. To evaluate the combined activity of the antibodies of the invention In vitro neutralization of FluAB_MLNS with the antivirals oseltamivir, zanamivir, or baloxavir marboxil was performed on representative H1N1 and H3N2 virus strains to evaluate the inhibitory effect. Combined effect analysis was performed using median effect plots and combination index (CI) calculations. Briefly, MDCK (Madin-Darby canine kidney) cells were seeded at 30,000 cells / well into 96-well plates (flat bottom, black). Cells were cultured at 37°C 5% CO2 overnight. Twenty-four hours later, 4x dilutions of antibodies and antivirals (oseltamivir, zanamivir or baloxavir marboxil) in 60 pi infection medium (MEM (Sigma Aldrich, cat. n. M0644) + Glutamax (Invitrogen, 41090-028) + 1 g / ml TPCK-treated Trypsin (Worthington Biochemical #LS003750) + 10 g / ml Kanamycin) were prepared using serial 1:2 dilutions of FluAB_MLNS (starting from 166.7 nM final, 9 horizontal spots) and different antivirals (oseltamivir, zanamivir or baloxavir marboxil), starting from 125 (250 for zanamivir) nM with 7 vertical spots), according to the plate scheme shown in Figure 7. For each combination, three independent plates were prepared, to have triplicates of each drug-drug combination ratio. Single compound titrations (i.e., FluAB_MLNS, 9 points and each antiviral, 8 points) were included in each plate. Virus solutions were prepared at a concentration of 120x TCID50 in 60 pl, further diluted either 1:1 in MEM or mixed 1:1 with the FluAB_MLNS dilution and incubated for 1 hour at 33°C. Cells were washed twice using 200 pl / well of MEM without supplements, followed by the addition of 100 pl of virus alone or 100 pl of FluAB_MLNS / virus mix (100x TCID50 / well) and incubated for 4 hours at 33°C 5% CO2. After the addition of 100 pl / well of infection medium, cells were further incubated for 72 hours at 33°C 5% CO2.On day 3 after infection, 20 μΜ MuNANA (4-MUNANA (2-(4-Methylumbelliferyl)-aD-Nacetylneuraminic acid sodium salt hydrate (Sigma-Aldrich) #69587)) was prepared in MuNANA buffer (MES 32.5 mM / CaCl24 mM, pH 6.5) and 50 μl / well was poured into a black 96-well plate. Fifty μl of neutralization or virus-alone titration supernatant was transferred to the plate and incubated for 60 min at 37 °C. The reaction was then stopped with 100 μl / well of 0.2 M glycine / 50% EtOH, pH 10.7. Fluorescence was measured at 460 nm with a fluorimeter (Bio-Tek). The virus neutralization fraction is calculated according to the formula: i-fAz^. k fmax / where fx = sample fluorescence signal (cells + virus + FluAB_MLNS + antivirus); fmin = minimum fluorescence signal (cells only, no virus); fmax = maximum fluorescence signal (cells only + virus). The neutralized fraction data were used to calculate a quantitative analysis of dose-effect relationships for drug combinations according to the method of Chou and Talalay (Chou TC, Talalay P: Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv. Enzyme Regul. 1984, 22:27-55). The combination index, affected fraction (Fa), and isobologram were obtained using CompuSyn software (ComboSyn Inc., Paramus, NJ, USA) (Chou TC: Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacological Reviews 2006, 58:621-681). The results are shown in Figure 8 - 2 6 and are described below . Combination of FluAB MLNS and oseltamivir The relative efficacy of FluAB_MLNS and oseltamivir for neutralizing influenza A virus was compared in vitro on two representative virus serotypes for H3N2 and H1N1 strains. As shown in Figure 8, both compounds, tested separately, dose-dependently inhibited cell infection completely when independently exposed to H3N3 and H1N1 viruses (Figure 8A,B). The IC50 values, calculated from the median effect plot (Figure 8C,D) after log linearization of the data (as described in (Chou TC, Talalay P: Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv. Enzyme Regul. 1984, 22:27-55) were indeed in the nanomolar range for FluAB_MLNS (17.9 and 15.6 nM for H3 and H1 strains, respectively) and oseltamivir (7 and 9.1 nM for H3 and H1 strains, respectively).Overall, no substantial differences were measured in terms of inhibitory response by FluAB_MLNS between H3 and H1 virus infections, while H1N1 viruses appeared slightly more sensitive to the inhibitory effect of oseltamivir. To test the combined effect of FluAB_MLNS and oseltamivir in neutralizing MDCK cell infection with H3 and H1 viruses, both compounds were serially diluted at different ratios as described above, and assessed for neuraminidase enzymatic activity (NA; as a readout of the viral content in the culture) in the presence of different drug concentrations and compared with the effect of either drug alone. The neutralization effect measured with FluAB_MLNS was greatly enhanced in the presence of heteromolar concentrations of both compounds simultaneously, thus indicating a synergistic rather than additive effect, in both H3 and H1 virus infections (Figure 9). Slightly different susceptibility of H1 and H3 viruses to the inhibitory action of oseltamivir was detected. To precisely quantify the putative synergistic effect of various drug combination ratios, the neutralization data were further transformed according to the median effect principle and analyzed with CompuSyn software as described above. The effects of several different constant ratios of the FluAB_MLNS-oseltamivir combination were plotted in a median effect plot as shown in Figure 10. CompuSyn software applies a logarithmic transformation of the median effect equation to the experimental data and calculates the potency (IC50) and the so-called combination index (CI) of various drug combinations. CI is a derived parameter of the Chou-Talalay equation (median effect) that takes into account the physicochemical properties of the law of mass action and results from the sum of two ratios between the portion of the dose of drug 1 combined with drug 2 to achieve a certain effect divided by the single doses of drugs 1 and 2 to obtain the same effect. According to this mathematical algorithm, CI = 1 indicates an addictive effect, CI < 1 indicates synergism and CI > 1 indicates antagonism. As shown in Figures 11 and 12, for all tested combination ratios and for both H1 (Figure 11) and H3 (Figure 12) viruses, the predicted CI values ​​across the range of inhibited fractions depict curves well below 1 for all drug combination ratios, and the actual experimental points of different combined concentrations also range below 1 for almost all combinations. Overall, the data demonstrate a direct synergistic effect of FluAB_MLNS and oseltamivir when combined. The same data can be alternatively described with isobologram plots, which compare the equipotential concentrations of the single drugs and the combination drugs. As shown in Figures 13 and 14, the distribution of IC50, IC75, and IC90 values ​​for the three different combination ratios is well below the isobolite line connecting the IC50, IC75, and IC90 of the tested single drugs, respectively, for both H1 (Figure 13) and H3 (Figure 14), indicating consistent synergy (while additivity and antagonism would result in equipotency points localized at or above the isobolite of the single drugs, respectively). Combination of FluAB MLNS and zanamivir The relative efficacy of FluAB_MLNS and zanamivir for neutralizing influenza A virus was also compared in vitro on two representative virus serotypes for H3N2 and H1N1 strains. As shown in Figure 15, both compounds tested separately, in a dose-dependent manner, were able to completely inhibit cell infection, when independently exposed together with H3N3 and H1N1 viruses. The calculated relative IC50 values ​​were 23.1–24.4 nM for FluAB_MLNS and 10.7–13.7 nM for zanamivir. For the combined effect of FluAB_MLNS and zanamivir Figure 16 shows that, similar to oseltamivir, zanamivir greatly enhanced the inhibitory capacity of FluAB_MLNS against both H1 and H3 viruses. Quantification of the synergistic effect was calculated in a similar manner to CompuSyn and the median effect principle as described above. The median effect plot for the combined effect of FluAB_MLNS and zanamivir is shown in Figure 17. The CI calculations for FluAB_MLNS and zanamivir are shown in Figures 18 and 19 and clearly demonstrate a synergistic effect between the two drugs, both with H1 (Figure 18) and H3 viruses (Figure 19), as indicated by values ​​lower than 1 for all experimental points tested. Consistently, with both virus strains, the isobolograms show a strong synergistic effect across the IC50, IC75, and IC90 values ​​(shown in Figures 20 and 21), all of which are significantly below the IC values ​​with either drug alone. Combination of FluAB MLNS and baloxavir marboxil The recently approved endonuclease inhibitor baloxavir marboxil was initially compared with FluAB_MLNS alone in H1 and H3 strains, similar to that described above for oseltamivir and zanamivir. The results are shown in Figure 22. The calculated relative IC50 values ​​were 20.1–15.4 nM for FluAB_MLNS and 4.9–2.3 nM for baloxavir marboxil. Although Baloxavir has a different mechanism of action in inhibiting viral replication compared to NA inhibitors, the drug was still able to strongly enhance the inhibitory capacity of FluAB_MLNS, clearly indicating a synergistic effect (Figure 23). The inhibition data obtained with different combination ratios were used to calculate and plot the median effect with CompuSyn software and account for the type of drug-drug interaction as described above (Figure 24). The calculated CIs for FluAB_MLNS and baloxavir marboxil (Figure 25) clearly indicate a synergistic effect between the two drugs, both against H1 and H3 viruses, as indicated by values ​​lower than 1 for the majority of the experimental points tested. The isobolograms showed a strong and complete synergistic effect across all IC50, IC75, and IC90 values ​​(Figure 26). In summary, the neutralization capacity of FluAB_MLNS against H1 and H3 strains was synergistically enhanced by different antivirals, namely, the NA inhibitors oseltamivir and zanamivir and the endonuclease inhibitor baloxavir-marboxil. Example 7: Binding of human FcRn at different pH FluAB_wt and FluAB_MLNS were compared side by side for their ability to bind the neonatal Fc receptor (FcRn) using biolayer interferometry (BLI). For this purpose, the binding of FluAB_wt and FluAB_MLNS to human FcRn was measured on an Octet RED96 instrument (biolayer interferometry, BLI, ForteBio). The biosensor coated with anti-human FabCH1 was pre-hydrated in kinetic buffer for 10 min at RT. Then, human mAb (FluAB_wt or FluAB_MLNS) was loaded at 1 pg / ml in kinetic buffer at pH 7.4 for 30 min onto the Biosensor. The baseline was measured in kinetic buffer (Sterile filtered 0.01% endotoxin-free bovine serum albumin, 0.002% Tween-20 (Polysorbate 20), 0.005% NaN3 in PBS) at pH=7.4 or pH=6.0 for 4 min. The human mAb sensor was then exposed for 7 minutes to a solution of human FcRn at 1 pg / ml in kinetics buffer at pH = 7.4 or pH = 6.0 to measure the FcRn-mAb association in different environments (on rate). Dissociation was then measured in kinetics buffer at the same pH for an additional 5 minutes (off rate). All steps were performed under stirring at 1000 rpm at 30°C.Association and dissociation profiles are measured in real time as changes in interference patterns. As shown in Figure 27, FluAB_MLNS binds human FcRn with higher affinity compared to FluAB_wt at acidic pH (pH 6.0), whereas neither FluAB_MLNS nor FluAB_wt binds FcRn at neutral pH (pH 7.4). Example 8: Characterization of polymorphisms identified in antibody epitope extension Historical polymorphisms in epitope extension were evaluated for their impact on the neutralization activity of FluAB_MLNS using viruses generated by reverse genetics with H1 HA or H3 HA on the A / Puerto Rico / 8 / 34 (PR8) background. Single nucleotide polymorphisms were introduced into the PR8 HI HA or A / Aichi / 2 / 68 (Aichi) HA pHW2000 plasmids using site-directed mutagenesis. Recombinant influenza A viruses were rescued with H1 or H3 HA linked to the PR8 frame using standard methods (e.g., as described in Hoffmann, Gabriele Neumann, Yoshihiro Kawaoka, Gerd Hobom, Robert G. Webster, 2000, A DNA transfection system for generation of influenza A virus from eight plasmids. Proceedings of the National Academy of Sciences May 2000, 97 (11): 6108-6113; doi: 10.1073 / pnas.100133697). Neutralization activity is evaluated in MDCK cells using standard methods. For example, neutralization activity can be evaluated in MDCK cells, e.g., in 96-well plates. For this purpose, MCDK cells can be seeded at 30,000 cells / well 24 hours before infection. FluAB_MLNS antibody can be incubated with the virus for 1 hour at 37°C before addition to MDCK cells. For this purpose, 1:2.5 9-point serial dilutions of FluAB_MLNS can be prepared in infection medium and each dilution can be tested in triplicate (e.g., final concentration 50 pg / mL - 0.03 pg / mL) and can be incubated with 120 TCID50 virus for 1 hour at 37°C. MDCK cells can be washed twice with PBS, 100 pl / well of virus:antibody solution can be added, and the cells can be incubated for 4 hours at 37°C. After 4 hours, an additional 100 pl / well of infection medium can be added to the cells. After 72 hours of incubation at 37°C, viral RNA can be extracted and quantified by qRT-PCR, i.e.using WHO primers (World Health Organization. CDC real-time RT-PCR protocol for influenza A H1N1. April 28, 2009). IC50 is expressed as the antibody concentration in pg / mL that reduces 50% of viral replication and can be calculated using a non-linear 4-parameter logistic curve fit of data normalized to control wells (no virus and virus only). The neutralization activity of FluAB_MLNS polymorphisms to H1 and H3 HA at the extended epitope is shown in Table 4 below. Virus Amino Acid Changes in HA FluAB_MLNS Neutralization Geomean IC50 (pg / mL) Multiple change relative to WT virus PR8:Aichi HA wt wild type 5.6 NA PR8:Aichi HA P11S P11S 9.5 1.7 PR8:Aichi HA D46N D46N 3.3 0.6 PR8:Aichi HA N49T N49T 5.0 0.9 PR8 wt wild type 4.7 NA PR8 HA N146D N146D 5.5 1.2 Table 4. Aichi = A / Aichi / 2 / 68; Geomean = geometric mean; HA = hemagglutinin; NA = not applicable; PR8 = A / Puerto Rico / 8 / 34 H1N1; wt = wild type For viruses encoding H3 HA, FluAB_MLNS neutralized viruses with HA1 P11S, HA2 D46N, or HA2 N49T mutations with IC50 values ​​similar to wild-type viruses (<2-fold IC50 change relative to wild-type viruses). For viruses encoding H1 HA, FluAB_MLNS neutralized viruses encoding HA2 N146D with IC50 values ​​similar to wild-type viruses (<2-fold IC50 change relative to wild-type viruses). In addition, the wild-type PR8 strain used encoded the HA2 L38Q and D46N polymorphisms and was neutralized with an IC50 value of 4.7 pg / mL by FluAB_MLNS. Overall, all evaluated polymorphisms resulted in an IC50 fold change <2 relative to wild-type viruses for FluAB_MLNS. In summary, FluAB_MLNS effectively neutralized all evaluated historical polymorphisms in the extended epitopes (H3 HA: HA1 P11S, HA2 D4 6N, or HA2 N49T; H1 HA: N146D). Example 9: Anti-drug antibody response in Tg32 mice Regarding the M428L / N434S mutation, concerns have recently been raised that it increases the immunogenicity of antibodies containing this mutation (Brian C. Mackness, Julie A. Jaworski, Ekaterina Boudanova, Anna Park, Delphine Valente, Christine Mauriac, Olivier Pasquier, Thorsten Schmidt, Mostafa Kabiri, Abdullah Kandira, Katarina Radosevic & Huawei Qiu (2019) Antibody Fc engineering for enhanced neonatal Fc receptor binding and prolonged circulation half-life, mAbs, 11:7, 1276-1288; Maeda A, Iwayanagi Y, Haraya K, et al. Identification of human IgG1 variant with enhanced FcRn binding and without increased binding to rheumatoid factor autoantibody. MAbs. 2017;9(5):844—853). To assess the immunogenicity, specifically the antidrug response (anti-drug antibody; ADA), of the FluAB_MLNS antibody compared to its parent antibody FluAB_wt, two separate groups (n=5) of TG32 mice (transgenic for human FcRn) were injected with 5 mg / kg of the monoclonal antibody FluABMLNS or FluAB_wt. To evaluate the circulating levels of the injected mAbs, blood samples were then obtained at different time points. Samples taken on days 14 and 21 post-injection were used to evaluate, by specific ELISA, the anti-drug antibody (ADA) response to the injected human monoclonal. Briefly, purified FluAB_wt and FluAB_MLNS monoclonal antibodies were coated on 96-well plates at 2 pg / ml. After blocking, sera from treated animals were obtained 14 and 21 days post-injection, diluted 1:180, and incubated for 1.5 hours at room temperature (RT). After washing, a peroxidase-labeled goat anti-mouse IgG F(ab')2 fragment (0.16 pg / ml) was added to the plate and incubated for 1.5 hours at RT. ADA IgG (murine antibodies against injected antibodies FluAB_wt and FluAB_MLNS) was then expressed with appropriate substrates and read with a spectrophotometer. Data shown are OD values ​​(450 nm) obtained on each individual serum (n=5 / group) collected 14 and 21 days after iv antibody administration. Sera from naive Tg32 mice (ctrl) were used as negative controls. The results are shown in Figure 28. Surprisingly, the murine serum IgG signal reacting to the FluAB-MLNS antibody was very low and corresponded to the signal detected in uninjected control animals, whereas the ADA response measured in the serum of mice injected with FluAB_wt, on the contrary, was significantly high, both 14 and 21 days after iv injection (Figure 28A). Furthermore, ADA levels measured on day 14 post-injection were significantly and inversely correlated with circulating FluAB_wt levels (serum FluAB_wt levels decreased due to murine antibodies against FluAB_wt), whereas circulating FluAB-MLNS levels measured at the same time were indeed much higher and homogeneous (Figure 28B). In summary, these data demonstrate that surprisingly the anti-drug response (anti-drug antibodies; ADA), and, thus, the immunogenicity of FluAB_MLNS is decreased compared to FluAB_wt. Example 10: Anti-drug antibody response and immunogenicity after sc administration To further confirm this surprising finding in a more immunogenic setting, separate groups of TG32 mice (n=5) were injected with FluAB-MLNS or FluAB_wt (5 mg / kg) subcutaneously (s.c.), which is generally considered a more immunogenic route of administration. Three weeks after s.c. administration, anti-drug antibody levels were measured in serum by a mouse anti-drug-specific ELISA (as described above in Example 9) in sera from mice injected s.c. with FluAB_wt or FluAB_MLNS. As negative controls, 10 sera from naive, untreated animals were used. The results are shown in Figure 29. Despite the more immunogenic setting, animals treated sc with FluAB-MLNS still did not mount a humoral immunogenic response, as confirmed by serum titers of anti-hIgG antibodies that overlapped with those detected in the sera of uninjected control animals. In contrast, ADA titers in animals treated with FluAB_wt were clearly positive and measurable in all treated animals. An inverse correlation between circulating levels of injected antibodies and endogenous anti-hIgG responses was detected in the sera of mice injected 5 with FluAB_wt alone (not shown). These data surprisingly show that the FluAB_MLNS antibody exhibits less immunogenicity compared to its parent antibody FluAB_wt. SEQ LIST AND SEQ ID NUMBER (SEQ LIST): SEQ ID NO: SYNAVWN CDRH1 SEQ ID NO: RTYYRS GWYNDYAE SVKS CDRH2 SEQ ID NO: SGHITVF GVNVDAFDM CDRH3 SEQ ID NO: RTSQSLSSYTH CDRL1 SEQ ID NO: AASSRGS CDRL2 SEQ ID NO: 7 QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSY NAVWNWIRQSPSRGLEWLGRTYYRSGWYNDYA ESVKSRITINPDTSKNQFSLQLNSVTPEDTAV YYCARS GHITVF GVNVDAFDMWGQGTMVTVS S VH SEQ ID NO: 8 DIQMTQSPSSLSASVGDRVTITCRTSQSLSSY THWYQQKPGKAPKLLIYAASSRGSGVPSRFSG SGSGTDFTLTISSLQPEDFATYYCQQSRTFGQ GTKVEIK VL SEQ ID NO: 9 QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSY NAVWNWIRQSPSRGLEWLGRTYYRSGWYNDYA ESVKSRITINPDTSKNQFSLQLNSVTPEDTAV YYCARS GHITVF GVNVDAFDMWGQGTMVTVS S ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDK RVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW YVD GVEVHNAKTKP REEQYN STYRVVSVL TVL HQDWLNGKEYKCKVSNKALPAPIEKTISKAKG QPREP QVYTLPP SREEMTKNQVSLTC LVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFF LYSKLTVDKSRWQQGNVFSCSVLHEALHSHYT QKSLSLSPGK Rantai berat SEQ ID NO: 10 DIQMTQSPSSLSASVGDRVTITCRTSQSLSSY THWYQQKPGKAPKLLIYAASSRGSGVPSRFSG SGSGTDFTLTISSLQPEDFATYYCQQSRTFGQ GTKVEIKRTVAAPSVFIFPPSDEQLKSGTASV VCLLNNFYPREAKVQWKVDNALQSGNSQESVT EQDSKDSTYSLSSTLTLSKADYEKHKVYACEV THQGLSSPVTKSFNRGEC Light chain FluAB_wt SEQ ID NO: 11 QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSY NAVWNWIRQSPSRGLEWLGRTYYRSGWYNDYA ESVKSRITINPDTSKNQFSLQLNSVTPEDTAV YYCARS GHITVF GVNVDAFDMWGQGTMVTVS S ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDK RVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW YVD GVEVHNAKTKP REEQYN STYRVVSVL TVL HQDWLNGKEYKCKVSNKALPAPIEKTISKAKG QPREP QVYTLPP SREEMTKNQVSLTC LVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFF LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYT QKSLSLSPGK Heavy chain nucleic acid sequence FluAB_MLNS SEQ ID NO: 12 CAAGTTCAGCTGCAGCAGAGCGGCCCCGGTCT GGTGAAGCCTAGCCAGACTCTGTCTTTAACTT GCGCCATCTCCGGCGACAGCGTGAGCAGCTAC AACGCCGTCTGGAACTGGATTCGTCAGAGCCC TGCAGAGGTTTAGAGTGGCTGGGTCGTACTT ACTATCGTTCCGGCTGGTACAACGACTACGCCCC GAGAGCGT GAAG TCTCGTATCACTATCAACCC CGATACTAG CAAGAAC CAGTTCTCTTTACAGC TGAACAGCGTGACTCCCGAAGACACTGCCGTG TACTACTGCGCTCGTAGCGGCCACATCACTGT GTTCGGCGTGAATGTGGACGCCTTCGACATGT GGGGCCAAGGTACTATGGTCACTGTGAGCAGC FluAB_MLNS VH nuc SEQ ID NO: 13 GACATCCAGATGACTCAGAGCCCTTCCTCTTT AAGCGCTAGCGTGGGCGATAGGGTCACTATCA CTTGTCGTACTAGCCAGTCTTTAAGCTCCTAC ACTCACTGGTACCAGCAGAAGCCCGGTAAGGC CCCTAAGCTGCTGATCTACGCTGCCAGCAGCA GAGGCAGCGGAGTGCCTAGCAGATTTAGCGGC AGCGGTAGCGGCACTGACTTCACTCTGACAAT FluAB_MLNS VL nuc 100 SEQ ID NO: 14 CAAGTTCAGCTGCAGCAGAGCGGCCCCGGTCT GGTGAAGCCTAGCCAGACTCTGTCTTTAACTT GCGCCATCTCCGGCGACAGCGTGAGCAGCTAC AACGCCGTCTGGAACTGGATTCGTCAGAGCCC TGCAGAGGTTTAGAGTGGCTGGGTCGTACTT ACTATCGTTCCGGCTGGTACAACGACTACGCCCC GAGAGCGT GAAG TCTCGTATCACTATCAACCC CGATACTAG CAAGAAC CAGTTCTCTTTACAGC TGAACAGCGTGACTCCCGAAGACACTGCCGTG TACTACTGCGCTCGTAGCGGCCACATCACTGT GTTCGGCGTGAATGTGGACGCCTTCGACATGT GGGGCCAAGGTACTATGGTCACTGTGAGCAGC GCTAGCACCAAGGGCCCATCGGTCTTCCCCCT GGCACCCTCCTCCAAGAGCACCTCTGGGGGCA CAGCGGCCCTGGGCTGCCTGGTCAAGGACTAC TTCCCCGAACCGGTGACGGTGTCGTGGAACTC AGGCGCCCTGACCAGCGGCGTGCACACCTCC CGGCCGTCCTACAGTCCTCAGGACTCTACTCC CTCAGCAGCGTGGTGACCGTGCCCTCCAGCAG CTTGGGCACCCAGACCTACATCTGCAACGTGA ATCACAAGCCCAGCAACACCAAGGTGGACAAG CGGGTTGAGCCCAAATCTTGTGACAAAACTCA CACATGCCCACCGTGCCCAGCACCTGAACTCC TGGCGGGACCGTCAGTCTTCCTCTTCCCCCCA AAACCCAAGGACACCCTCATGATCTCCCGGAC CCCTGAGGTCACATGCGTGGTGGTGGACGTGA GCCACGAAGACCCTGAGGTCAAGTTCAACTGG TACGTGGACGGCGTGGAGGTGCATAATGCCAA GACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTG CACCAGGACTGGCTGAATGGCAAGGAGTACAA FluAB_MLNS rantai berat nuc 101 SEQ ID NO: 15 GACATCCAGATGACTCAGAGCCCTTCCTCTTT AAGCGCTAGCGTGGGCGATAGGGTCACTATCA CTTGTCGTACTAGCCAGTCTTTAAGCTCCTAC ACTCACTGGTACCAGCAGAAGCCCGGTAAGGC CCCTAAGCTGCTGATCTACGCTGCCAGCAGCA GAGGCAGCGGAGTGCCTAGCAGATTTAGCGGC AGCGGTAGCGGCACTGACTTCACTCTGACAAT CAGCTCTTTACAGCCCGAAGACTTCGCCACTT ACTACTGCCAGCAGTCTCGTACTTTCGGCCAA GGTACTAAGGTGGAGATCAAGCGTACGGTGGC TGCACCATCTGTCTTCATCTTCCCGCCATCTG ATGAGCAGTTGAAATCTGGAACTGCCTCTGTT GTGTGCCTGCTGAATAACTTCTATCCCAGAGA GGCCAAAGTACAGTGGAAGGTGGATAACGCCC TCCAATCGGGTAACTCCCAGGAGAGTGTCACA GAGCAGGACAGCAAGGACAGCACCTACAGCCT CAGCAGCACCCTGACGCTGAGCAAAGCAGACT ACGAGAAACACAAAGTCTACGCCTGCGAAGTC ACCCATCAGGGCCTGAGCTCGCCCGTCACAAA GAGCTTCAACAGGGGAGAGTGT FluAB_MLNS rantai ringan nuc

Claims

1. Antibodies consisting of the heavy chain sequences CDR1, CDR2, and CDR3 as specified in SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3; light chain sequences CDR1, CDR2, and CDR3 as specified in SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6; and mutations M428L and N434S in the heavy chain constant region.

2. The antibody of claim 1, wherein said antibody binds to the hemagglutinin of influenza A virus.

3. The antibodies of claim 1 or 2, wherein said antibodies neutralize influenza A virus infection.

4. The antibody of claim 3, wherein said antibody neutralizes influenza A infection at a dose, which does not exceed one-half of the dose required for neutralization of influenza A with a reference antibody, which differs from said antibody only in that it does not contain the M428L and N434S mutations in the constant region of the heavy chain.

5. The antibody of claim 4, wherein the dose does not exceed one-third of the dose required for neutralization of influenza A with said reference antibody.

6. The antibody of claim 4 or 5, wherein the dose does not exceed one-fifth of the dose required for neutralization of influenza A with said reference antibody.

7. An antibody of any of the preceding claims, wherein the antibody neutralizes the HA1 P11S, HA2 D46N, 103 and / or HA2 N49T polymorphisms of H3 HA; and / or the N146D polymorphism of H1 HA.

8. The antibody of any one of claim 7, wherein the antibody neutralizes the HA1 P11S, HA2 D46N, and / or HA2 N49T polymorphisms of H3 HA; and / or the N146D polymorphism of H1 HA with an IC50 change of <2 times relative to the HA of the wild-type virus.

9. The antibody of any of the preceding claims, wherein the antibody causes a decreased anti-drug antibody response compared to a comparative antibody that differs from said antibody only in that said antibody does not contain the M428L and N434S mutations in the heavy chain constant region.

10. An antibody of any of the foregoing claims, wherein the antibody exhibits lower immunogenicity compared to a comparative antibody that differs from said antibody only in not containing the M428L and N434S mutations in the constant region of the heavy chain.

11. Antibodies of any of the foregoing claims, wherein the antibodies are human antibodies.

12. Antibodies of any of the foregoing claims, wherein said antibodies are monoclonal antibodies.

13. Antibodies of any of the preceding claims, wherein the antibodies are of the IgG type.

14. The antibody of claim 13, wherein the antibody is type 104 IgG1.

15. Antibodies of any of the preceding claims, wherein the light chain of the antibody is a kappa light chain.

16. An antibody of any of the preceding claims, wherein the antibody comprises a heavy chain variable region comprising an amino acid sequence having at least 70% identity to SEQ ID NO: 7 and a light chain variable region comprising an amino acid sequence having at least 70% identity to SEQ ID NO: 8, wherein the CDR sequence as defined in claim 1 is retained.

17. An antibody of any of the preceding claims, wherein the antibody comprises a heavy chain variable region comprising an amino acid sequence having at least 75% identity to SEQ ID NO: 7 and a light chain variable region comprising an amino acid sequence having at least 75% identity to SEQ ID NO: 8, wherein the CDR sequence as defined in claim 1 is retained.

18. An antibody of any of the preceding claims, wherein the antibody comprises a heavy chain variable region comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 7 and a light chain variable region comprising an amino acid sequence having at least 80% identity to SEQ ID NO: 8, wherein the CDR sequence as defined in claim 1 is retained.

19. An antibody of any of the preceding claims, wherein the antibody comprises a heavy chain variable region comprising an amino acid sequence having at least 85% 105 identity to SEQ ID NO: 7 and a light chain variable region comprising an amino acid sequence having at least 85% identity to SEQ ID NO: 8, wherein the CDR sequence as defined in claim 1 is retained.

20. An antibody of any of the preceding claims, wherein the antibody comprises a heavy chain variable region comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 7 and a light chain variable region comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 8, wherein the CDR sequence as defined in claim 1 is retained.

21. An antibody of any of the preceding claims, wherein the antibody comprises a heavy chain variable region comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 7 and a light chain variable region comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 8, wherein the CDR sequence as defined in claim 1 is retained.

22. An antibody of any of the preceding claims, wherein the antibody comprises a heavy chain variable region comprising an amino acid sequence as set forth in SEQ ID NO: 7 and a light chain variable region comprising an amino acid sequence as set forth in SEQ ID NO: 8, wherein the CDR sequence as defined in claim 1 is retained.

23. The antibody of any one of the foregoing claims, wherein the CH3 region of the antibody does not comprise further mutations other than M428L and N434S. 106 24. Antibodies of any of the foregoing claims, wherein the Fc region of the antibody does not comprise further mutations other than M428L and N434S.

25. An antibody of any of the preceding claims, wherein the antibody comprises a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO: 9 and a light chain comprising an amino acid sequence as set forth in SEQ ID NO:

10.

26. An antibody of any of the preceding claims, wherein the antibody has a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO: 9 and a light chain comprising an amino acid sequence as set forth in SEQ ID NO:

10.

27. Antibodies of any of the foregoing claims for use in the prophylaxis or treatment of influenza A virus infection.

28. Antibodies for use according to claim 27, wherein the antibodies are administered prophylactically.

29. An antibody for use according to claim 27 or 28, wherein the antibody is administered at a dose not exceeding one-half of the dose required for prophylaxis or treatment of influenza A with a reference antibody, which differs from said antibody only in that it does not contain the M428L and N434S mutations in the constant region of the heavy chain.

30. An antibody for use according to claim 29, wherein said dose does not exceed one-third of the dose required for prophylaxis or treatment of influenza A with said reference antibody.

31. An antibody for use according to claim 29, wherein the dose does not exceed one-quarter of the dose required for prophylaxis or treatment of influenza A with said reference antibody.

32. An antibody for use according to claim 29, wherein the dose does not exceed one-fifth of the dose required for prophylaxis or treatment of influenza A with said reference antibody.

33. An antibody for use according to claim 29, wherein the dose does not exceed one-sixth of the dose required for prophylaxis or treatment of influenza A with said reference antibody.

34. An antibody for use according to claim 29, wherein the dose does not exceed one-seventh of the dose required for prophylaxis or treatment of influenza A with said reference antibody.

35. An antibody for use according to claim 29, wherein the dose does not exceed one-eighth of the dose required for prophylaxis or treatment of influenza A with said reference antibody.

36. An antibody for use according to claim 29, wherein the dose does not exceed one-ninth of the dose required for prophylaxis or treatment of influenza A with said comparator antibody 108.

37. An antibody for use according to claim 29, wherein the dose does not exceed one-tenth of the dose required for prophylaxis or treatment of influenza A with said reference antibody.

38. Antibodies for use according to any one of claims 27 - 37, wherein the subject to be treated is at immediate risk of influenza A infection.

39. Antibodies for use according to any one of claims 27 - 38, wherein the subject to be treated suffers from an autoimmune or allergic disease; or is at risk of developing an autoimmune or allergic disease.

40. A nucleic acid molecule comprising a polynucleotide encoding an antibody of any one of claims 1 - 26.

41. The nucleic acid molecule of claim 40, wherein the nucleic acid molecule comprises: (i) a polynucleotide comprising a nucleotide sequence as set forth in SEQ ID NO: 12; or a nucleotide sequence having 70% or more identity to SEQ ID NO: 12; and (ii) a polynucleotide comprising a nucleotide sequence as set forth in SEQ ID NO: 13; or a nucleotide sequence having 70% or more identity to SEQ ID NO:

13.

42. The nucleic acid molecule of claim 40 or 41, wherein 109 the nucleic acid molecule comprises (i) a polynucleotide comprising a nucleotide sequence as set forth in SEQ ID NO: 14; or a nucleotide sequence having 70% or more identity to SEQ ID NO: 14; and (ii) a polynucleotide comprising a nucleotide sequence as set forth in SEQ ID NO: 15; or a nucleotide sequence having 70% or more identity to SEQ ID NO:

15.

43. A combination of first and second nucleic acid molecules, wherein the first nucleic acid molecule comprises a polynucleotide encoding a heavy chain of an antibody of any one of claims 1 - 26; and the second nucleic acid molecule comprises a polynucleotide encoding a corresponding light chain of the same antibody.

44. The combination of the first and second nucleic acid molecules of claim 43, wherein (i) the first nucleic acid molecule comprises a polynucleotide comprising a nucleotide sequence as set forth in SEQ ID NO: 12; or a nucleotide sequence having 70% or more identity to SEQ ID NO: 12; and (ii) the second nucleic acid molecule comprises a polynucleotide comprising a nucleotide sequence as set forth in SEQ ID NO: 13; or a nucleotide sequence having 70% or more identity to SEQ ID NO:

13.

45. The combination of the first and second nucleic acid molecules of claim 43 or 44, wherein (i) the first nucleic acid molecule comprises a polynucleotide comprising a nucleotide sequence such as 110 set forth in SEQ ID NO: 14; or a nucleotide sequence having 70% or more identity to SEQ ID NO: 14; and (ii) the second nucleic acid molecule comprises a polynucleotide comprising a nucleotide sequence such as set forth in SEQ ID NO: 15; or a nucleotide sequence having 70% or more identity to SEQ ID NO:

15.

46. ​​A vector comprising a nucleic acid molecule of any one of claims 40 - 42.

47. A vector comprising a combination of nucleic acid molecules of any one of claims 43 - 45.

48. A cell expressing an antibody of any one of claims 1 - 26, or comprising a vector of claim 46 or 47.

49. A pharmaceutical composition comprising the antibody of any one of claims 1 - 26, the nucleic acid of any one of claims 40 - 42, the combination of nucleic acids of any one of claims 43 - 45, the vector of claim 46 or 47, or the cells of claim 48, and, optionally, a pharmaceutically acceptable diluent or carrier.

50. Use of the antibody of any one of claims 1 26, the nucleic acid of any one of claims 40 - 42, the combination of nucleic acids of any one of claims 43 - 45, the vector of claim 46 or 47, the cells of claim 48 or the pharmaceutical composition of claim 49 in the manufacture of a medicament for the prophylaxis, treatment or attenuation of influenza A virus infection.

51. The antibody of any one of claims 1 - 26, the nucleic acid of any one of claims 40 - 42, the combination of nucleic acids of any one of claims 43 - 45, the vector of claim 46 or 47, the cells of claim 48 or the pharmaceutical composition of claim 49 for use in the prophylaxis or treatment of influenza A virus infection.

52. Antibodies, nucleic acids, combinations of nucleic acids, vectors, cells or pharmaceutical compositions for use according to claim 51, wherein the antibodies, nucleic acids, vectors, cells or pharmaceutical compositions are administered prophylactically.

53. Antibodies, nucleic acids, combinations of nucleic acids, vectors, cells or pharmaceutical compositions for use according to claim 51 or claim 52, wherein the antibodies, nucleic acids, vectors, cells or pharmaceutical compositions are administered in combination with an antiviral.

54. Antibodies, nucleic acids, combinations of nucleic acids, vectors, cells or pharmaceutical compositions for use according to claim 53, wherein the antiviral is selected from neuraminidase inhibitors and influenza polymerase inhibitors.

55. Antibodies, nucleic acids, combinations of nucleic acids, vectors, cells or pharmaceutical compositions for use according to claim 53 or 54, wherein the antiviral is selected from oseltamivir, zanamivir and baloxavir.

56. Antibodies, nucleic acids, combinations of nucleic acids, vectors, cells or pharmaceutical compositions for use according to any one of claims 51 - 55, wherein the subject being treated suffers from an autoimmune or allergic disease; or is at risk of developing an autoimmune or allergic disease. 112 57. A combination of (i) an antibody of any one of claims 1 - 26, and (ii) an antiviral agent.

58. The combination of claim 57, wherein the antiviral is selected from a neuraminidase inhibitor and an influenza polymerase inhibitor.

59. The combination of claim 57 or 58, wherein the antiviral is selected from oseltamivir, zanamivir and baloxavir.

60. A combination of any one of claims 57 - 59 for use in the prophylaxis or treatment of influenza A virus infection.

61. A method for reducing influenza A virus infection, or reducing the risk of influenza A virus infection, comprising: administering to a subject in need thereof, a therapeutically effective amount of an antibody of any one of claims 1 - 26.

62. The method of claim 61, wherein the antibody is administered prophylactically.

63. The method of claim 61 or 62, wherein the antibody is administered at a dose not exceeding one-half of the dose required for prophylaxis or treatment of influenza A with a comparative antibody, which differs from said antibody only in that it does not contain the M428L and N434S mutations in the constant region of the heavy chain.

64. The method of claim 63, wherein the dose does not exceed 113 one-third of the dose required for prophylaxis or treatment of influenza A with said comparative antibody.

65. The method of claim 63, wherein the dose does not exceed one-fifth of the dose required for prophylaxis or treatment of influenza A with said comparative antibody.

66. The method of any one of claims 61 - 65, wherein the subject is at immediate risk of influenza A infection.

67. The method of any one of claims 61 - 66, wherein the antibody is administered in combination with an antiviral.

68. A method of decreasing the immunogenicity of an antibody comprising a heavy chain CDR1, CDR2, and CDR3 sequence as set forth in SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3; a light chain CDR1, CDR2, and CDR3 sequence as set forth in SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6; comprising the step of introducing M428L and N434S mutations in the constant region of the heavy chain of the antibody.