{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T06:15:49Z","timestamp":1788243349836,"version":"build-2803163510"},"reference-count":86,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Singapore Ministry of Health (MOH)\u2014National Centre for Infectious Diseases","award":["PREPARE-OC-VT-2022-010"],"award-info":[{"award-number":["PREPARE-OC-VT-2022-010"]}]},{"award":["PREPARE-OC-VT-2022-010"],"award-info":[{"award-number":["PREPARE-OC-VT-2022-010"]}],"id":[{"id":"https:\/\/ror.org\/03rtrce80","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Singapore Academies South-East Asia Fellowship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Neuraminidase (NA) is a major surface glycoprotein of influenza viruses that mediates the release of progeny virions from infected cells. Although both hemagglutinin (HA) and NA are targets of protective immune responses, current seasonal influenza vaccines are primarily standardized based on HA content, resulting in variable and often suboptimal induction of NA-specific immunity. Therefore, NA is subject to different immune pressures and exhibits distinct patterns of antigenic evolution. Increasing evidence suggests that neuraminidase-inhibiting (NAI) antibodies contribute to protection against influenza by limiting viral replication and reducing disease severity, particularly when HA antibodies are poorly matched to circulating strains. The recent emergence of highly pathogenic avian influenza (HPAI) H5N1 viruses with widespread transmission in dairy cattle and increasing zoonotic infections has renewed interest in understanding the extent of pre-existing human immunity to NA and its potential role in mitigating disease caused by emerging influenza viruses. However, the breadth of cross-reactive NA immunity against zoonotic influenza viruses remains incompletely understood. In this review, we summarize current knowledge of population immunity to influenza NA, with a focus on the roles of immune imprinting, natural infection, and seasonal vaccination in shaping NA-specific antibody responses. We further discuss the cross-reactivity of these antibodies against zoonotic influenza viruses and highlight the implications of NA immunity for pandemic preparedness.<\/jats:p>","DOI":"10.3390\/vaccines14090748","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:45:13Z","timestamp":1788241513000},"page":"748","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population Immunity to Influenza Neuraminidase: From Immune Imprinting to Pandemic Preparedness"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5443-5507","authenticated-orcid":false,"given":"Kong Yen","family":"Liew","sequence":"first","affiliation":[{"name":"Infectious Diseases Translational Research Programme and Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7801-474X","authenticated-orcid":false,"given":"Tri Komala","family":"Sari","sequence":"additional","affiliation":[{"name":"Infectious Diseases Translational Research Programme and Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore"},{"name":"Laboratory of Virology, Faculty of Veterinary Medicine, Udayana University, Denpasar 80234, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2278-4497","authenticated-orcid":false,"given":"Yee-Joo","family":"Tan","sequence":"additional","affiliation":[{"name":"Infectious Diseases Translational Research Programme and Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"ref_1","unstructured":"WHO (2026, July 26). Influenza (Seasonal). Available online: https:\/\/www.who.int\/en\/news-room\/fact-sheets\/detail\/influenza-(seasonal)."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"a038778","DOI":"10.1101\/cshperspect.a038778","article-title":"Influenza Hemagglutinin Structures and Antibody Recognition","volume":"10","author":"Wu","year":"2020","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.chom.2025.12.006","article-title":"Molecular basis of 60 years of antigenic evolution of human influenza A(H3N2) virus neuraminidase","volume":"34","author":"Rosu","year":"2026","journal-title":"Cell Host Microbe"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"20748","DOI":"10.1073\/pnas.1113801108","article-title":"Discordant antigenic drift of neuraminidase and hemagglutinin in H1N1 and H3N2 influenza viruses","volume":"108","author":"Sandbulte","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.it.2023.11.001","article-title":"Targeting neuraminidase: The next frontier for broadly protective influenza vaccines","volume":"45","author":"Wu","year":"2024","journal-title":"Trends Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2290","DOI":"10.1093\/cid\/ciz639","article-title":"Pre-existing Antineuraminidase Antibodies Are Associated With Shortened Duration of Influenza A(H1N1)pdm Virus Shedding and Illness in Naturally Infected Adults","volume":"70","author":"Maier","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e00417-16","DOI":"10.1128\/mBio.00417-16","article-title":"Evaluation of Antihemagglutinin and Antineuraminidase Antibodies as Correlates of Protection in an Influenza A\/H1N1 Virus Healthy Human Challenge Model","volume":"7","author":"Memoli","year":"2016","journal-title":"mBio"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1093\/infdis\/jiv195","article-title":"Antibody to Influenza Virus Neuraminidase: An Independent Correlate of Protection","volume":"212","author":"Monto","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Abbadi, N., and Mousa, J.J. (2023). Broadly Protective Neuraminidase-Based Influenza Vaccines and Monoclonal Antibodies: Target Epitopes and Mechanisms of Action. Viruses, 15.","DOI":"10.3390\/v15010200"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"12665","DOI":"10.1128\/JVI.78.22.12665-12667.2004","article-title":"Neuraminidase Is Important for the Initiation of Influenza Virus Infection in Human Airway Epithelium","volume":"78","author":"Matrosovich","year":"2004","journal-title":"J. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8871","DOI":"10.1038\/s41467-024-53301-6","article-title":"A human monoclonal antibody targeting the monomeric N6 neuraminidase confers protection against avian H5N6 influenza virus infection","volume":"15","author":"Wang","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1038\/s41564-017-0011-8","article-title":"Broadly protective murine monoclonal antibodies against influenza B virus target highly conserved neuraminidase epitopes","volume":"2","author":"Wohlbold","year":"2017","journal-title":"Nat. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1038\/s41564-019-0401-1","article-title":"Antigenic drift originating from changes to the lateral surface of the neuraminidase head of influenza A virus","volume":"4","author":"Yasuhara","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.humimm.2009.06.004","article-title":"Genome-wide screening of human T-cell epitopes in influenza A virus reveals a broad-spectrum of CD4+ T cell responses to internal proteins, hemagglutinins and neuraminidases","volume":"70","author":"Babon","year":"2009","journal-title":"Hum. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.meegid.2010.10.013","article-title":"Identification of immunogenic consensus T-cell epitopes in globally distributed influenza-A H1N1 neuraminidase","volume":"11","author":"Gupta","year":"2011","journal-title":"Infect. Genet. Evol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.1016\/j.ymthe.2023.03.012","article-title":"Neuraminidase delivered as an APC-targeted DNA vaccine induces protective antibodies against influenza","volume":"31","author":"Werninghaus","year":"2023","journal-title":"Mol. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1007\/s40265-024-02083-8","article-title":"Influenza Vaccine Effectiveness and Progress Towards a Universal Influenza Vaccine","volume":"84","author":"Cowling","year":"2024","journal-title":"Drugs"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/s44298-025-00138-5","article-title":"Highly pathogenic avian influenza H5N1 in the United States: Recent incursions and spillover to cattle","volume":"3","author":"Mostafa","year":"2025","journal-title":"npj Viruses"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.tim.2014.01.010","article-title":"Bat-derived influenza-like viruses H17N10 and H18N11","volume":"22","author":"Wu","year":"2014","journal-title":"Trends Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"18903","DOI":"10.1073\/pnas.1212579109","article-title":"Crystal structures of two subtype N10 neuraminidase-like proteins from bat influenza A viruses reveal a diverged putative active site","volume":"109","author":"Zhu","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Tong, S., Zhu, X., Li, Y., Shi, M., Zhang, J., Bourgeois, M., Yang, H., Chen, X., Recuenco, S., and Gomez, J. (2013). New World Bats Harbor Diverse Influenza A Viruses. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003657"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e70192","DOI":"10.1111\/irv.70192","article-title":"Human Immune Response to Influenza Neuraminidase After Vaccination: A Systematic Review","volume":"19","author":"Ganesh","year":"2025","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/s41577-019-0143-6","article-title":"The human antibody response to influenza A virus infection and vaccination","volume":"19","author":"Krammer","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.chom.2024.12.004","article-title":"Identification of a broad-inhibition influenza neuraminidase antibody from pre-existing memory B cells","volume":"33","author":"Wang","year":"2025","journal-title":"Cell Host Microbe"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"eadx4810","DOI":"10.1126\/sciadv.adx4810","article-title":"Elucidating the characteristics and clonal evolutionary trajectory of influenza neuraminidase broadly reactive B cell","volume":"11","author":"Lin","year":"2025","journal-title":"Sci. Adv."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2844","DOI":"10.1128\/JVI.02163-13","article-title":"Genomewide Analysis of Reassortment and Evolution of Human Influenza A(H3N2) Viruses Circulating between 1968 and 2011","volume":"88","author":"Westgeest","year":"2014","journal-title":"J. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/S0140-6736(73)92196-X","article-title":"EFFECT OF NEURAMINIDASE ANTIBODY ON HONG KONG INFLUENZA","volume":"301","author":"Monto","year":"1973","journal-title":"Lancet"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5593","DOI":"10.1038\/s41467-024-49884-9","article-title":"A(H2N2) and A(H3N2) influenza pandemics elicited durable cross-reactive and protective antibodies against avian N2 neuraminidases","volume":"15","author":"Liang","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e1273","DOI":"10.1093\/infdis\/jiag030","article-title":"Cross-reactive H5N1 Neuraminidase Antibodies by Age and Influenza A Imprinting Cohorts of the Past Century: Population-Based Serosurvey, British Columbia, Canada","volume":"233","author":"Skowronski","year":"2026","journal-title":"J. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6320","DOI":"10.1038\/s41467-026-72941-4","article-title":"Cross-reactive human antibody responses to H5N1 influenza virus neuraminidase are shaped by immune history","volume":"17","author":"Ort","year":"2026","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/s12276-021-00603-0","article-title":"The evolution and future of influenza pandemic preparedness","volume":"53","author":"Harrington","year":"2021","journal-title":"Exp. Mol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e0044526","DOI":"10.1128\/mbio.00445-26","article-title":"Population immunity to clade 2.3.4.4b H5N1 is dominated by anti-neuraminidase antibodies","volume":"17","author":"Singh","year":"2026","journal-title":"mBio"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e0214525","DOI":"10.1128\/mbio.02145-25","article-title":"Low levels of influenza H5N1 HA and NA antibodies in the human population are boosted by seasonal H1N1 infection but not by H3N2 infection or influenza vaccination","volume":"16","author":"Werner","year":"2025","journal-title":"mBio"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e02281-16","DOI":"10.1128\/mBio.02281-16","article-title":"Analysis of Anti-Influenza Virus Neuraminidase Antibodies in Children, Adults, and the Elderly by ELISA and Enzyme Inhibition: Evidence for Original Antigenic Sin","volume":"8","author":"Rajendran","year":"2017","journal-title":"mBio"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e01385-19","DOI":"10.1128\/JVI.01385-19","article-title":"Hemagglutinin and Neuraminidase Antibodies Are Induced in an Age- and Subtype-Dependent Manner after Influenza Virus Infection","volume":"94","author":"Wong","year":"2020","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e02332-17","DOI":"10.1128\/mBio.02332-17","article-title":"NAction! How Can Neuraminidase-Based Immunity Contribute to Better Influenza Virus Vaccines?","volume":"9","author":"Krammer","year":"2018","journal-title":"mBio"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Mokalla, V.R., Gundarapu, S., Kaushik, R.S., Rajput, M., and Tummala, H. (2025). Influenza Vaccines: Current Status, Adjuvant Strategies, and Efficacy. Vaccines, 13.","DOI":"10.3390\/vaccines13090962"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"S75","DOI":"10.1093\/infdis\/jiz017","article-title":"Neuraminidase, the Forgotten Surface Antigen, Emerges as an Influenza Vaccine Target for Broadened Protection","volume":"219","author":"Eichelberger","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cell.2018.03.030","article-title":"Influenza Infection in Humans Induces Broadly Cross-Reactive and Protective Neuraminidase-Reactive Antibodies","volume":"173","author":"Chen","year":"2018","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"127918","DOI":"10.1016\/j.vaccine.2025.127918","article-title":"Characteristics of neuraminidase-specific immune responses in influenza vaccinated or naturally infected populations in Shenzhen, China","volume":"69","author":"Deng","year":"2026","journal-title":"Vaccine"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/s43856-026-01610-w","article-title":"Influenza vaccine responses differ between young children previously exposed to influenza antigens via infection versus vaccination","volume":"6","author":"Fox","year":"2026","journal-title":"Commun. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1016\/j.vaccine.2014.01.078","article-title":"Stability of neuraminidase in inactivated influenza vaccines","volume":"32","author":"Sultana","year":"2014","journal-title":"Vaccine"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e0122726","DOI":"10.1128\/spectrum.01227-26","article-title":"ELISA-based quantification of neuraminidase in commercial influenza vaccines using virus-derived reference antigens","volume":"14","author":"Kang","year":"2026","journal-title":"Microbiol. Spectr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.vaccine.2012.10.065","article-title":"Randomized Comparative Study of the Serum Antihemagglutinin and Antineuraminidase Antibody Responses to Six Licensed Trivalent Influenza Vaccines","volume":"31","author":"Couch","year":"2012","journal-title":"Vaccine"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Bethell, D., Saunders, D., Jongkaewwattana, A., Kramyu, J., Thitithayanont, A., Wiboon-ut, S., Yongvanitchit, K., Limsalakpetch, A., Kum-Arb, U., and Uthaimongkol, N. (2013). Evaluation of In Vitro Cross-Reactivity to Avian H5N1 and Pandemic H1N1 2009 Influenza Following Prime Boost Regimens of Seasonal Influenza Vaccination in Healthy Human Subjects: A Randomised Trial. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059674"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1093\/infdis\/jiw105","article-title":"Modest Waning of Influenza Vaccine Efficacy and Antibody Titers During the 2007\u20132008 Influenza Season","volume":"214","author":"Petrie","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3034","DOI":"10.1016\/j.vaccine.2018.04.017","article-title":"Responses to live attenuated influenza vaccine in children vaccinated previously with Pandemrix (ASO3B adjuvanted pandemic A\/H1N1pdm09)","volume":"36","author":"Southern","year":"2018","journal-title":"Vaccine"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2660","DOI":"10.1016\/j.vaccine.2020.02.024","article-title":"Use of traditional serological methods and oral fluids to assess immunogenicity in children aged 2\u201316 years after successive annual vaccinations with LAIV","volume":"38","author":"Hoschler","year":"2020","journal-title":"Vaccine"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1093\/infdis\/jis641","article-title":"Localized Mucosal Response to Intranasal Live Attenuated Influenza Vaccine in Adults","volume":"207","author":"Garrido","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1093\/cid\/ciy1003","article-title":"Immunogenicity and Viral Shedding of Russian-Backbone, Seasonal, Trivalent, Live, Attenuated Influenza Vaccine in a Phase II, Randomized, Placebo-Controlled Trial Among Preschool-Aged Children in Urban Bangladesh","volume":"69","author":"Lewis","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Desheva, Y., Smolonogina, T., Donina, S., and Rudenko, L. (2020). Study of Neuraminidase-Inhibiting Antibodies in Clinical Trials of Live Influenza Vaccines. Antibodies, 9.","DOI":"10.3390\/antib9020020"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1093\/cid\/ciy1007","article-title":"The Potential of Live, Attenuated Influenza Vaccine for the Prevention of Influenza in Children","volume":"69","author":"Belshe","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1093\/cid\/ciy1004","article-title":"The Effect of Preexisting Immunity on Virus Detection and Immune Responses in a Phase II, Randomized Trial of a Russian-Backbone, Live, Attenuated Influenza Vaccine in Bangladeshi Children","volume":"69","author":"Brickley","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Sergeeva, M.V., Romanovskaya-Romanko, E.A., Krivitskaya, V.Z., Kudar, P.A., Petkova, N.N., Kudria, K.S., Lioznov, D.A., Stukova, M.A., and Desheva, Y.A. (2023). Longitudinal Analysis of Neuraminidase and Hemagglutinin Antibodies to Influenza A Viruses after Immunization with Seasonal Inactivated Influenza Vaccines. Vaccines, 11.","DOI":"10.20944\/preprints202309.1919.v1"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1093\/infdis\/jiv313","article-title":"Persistence of Antibodies to Influenza Hemagglutinin and Neuraminidase Following One or Two Years of Influenza Vaccination","volume":"212","author":"Petrie","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/s41541-022-00500-1","article-title":"Antigenic comparison of the neuraminidases from recent influenza A vaccine viruses and 2019\u20132020 circulating strains","volume":"7","author":"Gao","year":"2022","journal-title":"npj Vaccines"},{"key":"ref_57","first-page":"RP105629","article-title":"The antigenic landscape of N1 neuraminidase in human influenza A virus strains isolated between 2009 and 2020","volume":"14","author":"Catani","year":"2025","journal-title":"eLife"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"RP90782","DOI":"10.7554\/eLife.90782","article-title":"The antigenic landscape of human influenza N2 neuraminidases from 2009 until 2017","volume":"12","author":"Catani","year":"2024","journal-title":"eLife"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"126269","DOI":"10.1016\/j.vaccine.2024.126269","article-title":"A recombinant N2 neuraminidase-based CpG 1018\u00ae adjuvanted vaccine provides protection against challenge with heterologous influenza viruses in mice and hamsters","volume":"42","author":"Hoxie","year":"2024","journal-title":"Vaccine"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/s41541-025-01209-7","article-title":"Immunogenicity and protective efficacy of an intranasal neuraminidase-based influenza vaccine with bacterial cell membrane-derived adjuvants","volume":"10","author":"Vasilev","year":"2025","journal-title":"npj Vaccines"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/s41541-026-01456-2","article-title":"A TRAC-478-adjuvanted recombinant N1 neuraminidase influenza virus vaccine induces balanced and broadly protective immune responses","volume":"11","author":"Hoxie","year":"2026","journal-title":"npj Vaccines"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1016\/j.vaccine.2023.02.034","article-title":"AF03 adjuvant improves anti-hemagglutinin and anti-neuraminidase immune responses induced by licensed seasonal quadrivalent influenza vaccines in mice","volume":"41","author":"Ustyugova","year":"2023","journal-title":"Vaccine"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Sandbulte, M.R., Jimenez, G.S., Boon, A.C.M., Smith, L.R., Treanor, J.J., and Webby, R.J. (2007). Cross-Reactive Neuraminidase Antibodies Afford Partial Protection against H5N1 in Mice and Are Present in Unexposed Humans. PLoS Med., 4.","DOI":"10.1371\/journal.pmed.0040059"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.2307\/1588829","article-title":"An inhibition test for identifying the neuraminidase antigen on influenza viruses","volume":"16","author":"Webster","year":"1972","journal-title":"Avian Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e00248-17","DOI":"10.1128\/CVI.00248-17","article-title":"Kinetics, Longevity, and Cross-Reactivity of Antineuraminidase Antibody after Natural Infection with Influenza A Viruses","volume":"24","author":"Changsom","year":"2017","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"168","DOI":"10.3201\/eid3001.230756","article-title":"Avian Influenza A(H5N1) Neuraminidase Inhibition Antibodies in Healthy Adults after Exposure to Influenza A(H1N1)pdm09","volume":"30","author":"Daulagala","year":"2024","journal-title":"Emerg. Infect. Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"10954","DOI":"10.1038\/s41467-025-66431-2","article-title":"Pre-existing cross-reactive immunity to highly pathogenic avian influenza 2.3.4.4b A(H5N1) virus in the United States","volume":"16","author":"Li","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2662076","DOI":"10.1080\/22221751.2026.2662076","article-title":"Neuraminidase-inhibiting antibodies boosted by H1N1pdm infection cross-react differently with H5N1 of clades 2.3.4.4b and 2.3.2.1a","volume":"15","author":"Liew","year":"2026","journal-title":"Emerg. Microbes Infect."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"101431","DOI":"10.1016\/j.lanmic.2026.101431","article-title":"Serum neutralisation of H5N1 clade 2.3.4.4b influenza is largely mediated by neuraminidase-directed antibodies","volume":"7","author":"Nair","year":"2026","journal-title":"Lancet Microbe"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"102638","DOI":"10.1016\/j.tmaid.2023.102638","article-title":"A comprehensive review of highly pathogenic avian influenza (HPAI) H5N1: An imminent threat at doorstep","volume":"55","author":"Charostad","year":"2023","journal-title":"Travel Med. Infect. Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e0030026","DOI":"10.1128\/msphere.00300-26","article-title":"Immunization with N2 neuraminidase can protect mice against a heterologous influenza A virus challenge even in the absence of cross-NA inhibiting antibodies","volume":"11","author":"Amelinck","year":"2026","journal-title":"mSphere"},{"key":"ref_72","first-page":"477","article-title":"Influenza A(H5N1) Immune Response among Ferrets with Influenza A(H1N1)pdm09 Immunity","volume":"31","author":"Sage","year":"2025","journal-title":"Emerg. Infect. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"eadw4856","DOI":"10.1126\/scitranslmed.adw4856","article-title":"Preexisting immunity to the 2009 pandemic H1N1 virus reduces susceptibility to H5N1 infection and disease in ferrets","volume":"17","author":"Restori","year":"2025","journal-title":"Sci. Transl. Med."},{"key":"ref_74","first-page":"458","article-title":"Effect of Prior Influenza A(H1N1)pdm09 Virus Infection on Pathogenesis and Transmission of Human Influenza A(H5N1) Clade 2.3.4.4b Virus in Ferret Model","volume":"31","author":"Sun","year":"2025","journal-title":"Emerg. Infect. Dis."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Wersebe, M.J., Paterson, N.M., Hassell, N., Zheng, X.-y., Rambo-Martin, B., Frederick, J.C., Lacek, K.A., Sullivan, A.H., Kirby, M.K., and Kondor, R. (2026). A newly emergent N1 neuraminidase associated with clade 2.3.4.4b highly pathogenic avian influenza A(H5) viruses in North America. medRxiv.","DOI":"10.64898\/2026.03.09.26347929"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Crespo-Bellido, A., Trov\u00e3o, N.S., Maksiaev, A., Baele, G., Dellicour, S., and Nelson, M.I. (2025). Emergence of D1.1 reassortant H5N1 avian influenza viruses in North America. bioRxiv.","DOI":"10.64898\/2025.12.19.695329"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"veaa046","DOI":"10.1093\/ve\/veaa046","article-title":"Genetic evolution and transmission dynamics of clade 2.3.2.1a highly pathogenic avian influenza A\/H5N1 viruses in Bangladesh","volume":"6","author":"Kwon","year":"2020","journal-title":"Virus Evol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Subedi, D., Thakur, S., Paudel, M., Gurung, P., Kafle, S., Bhattarai, S., Niraula, A., Marasini, H., Kandel, M., and Karki, S. (2026). A Global Review of Highly Pathogenic Avian Influenza (HPAI) and Control Strategies in Nepal. Zoonotic Dis., 6.","DOI":"10.3390\/zoonoticdis6020011"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1056\/NEJMc2504302","article-title":"Resurgence of Zoonotic Highly Pathogenic Avian Influenza A(H5N1) Virus in Cambodia","volume":"393","author":"Siegers","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"135","DOI":"10.3201\/eid3101.241210","article-title":"Influenza A(H5N1) Virus Clade 2.3.2.1a in Traveler Returning to Australia from India, 2024","volume":"31","author":"Deng","year":"2025","journal-title":"Emerg. Infect. Dis."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Koirala, P., Maharjan, M., Chapagain, S., Sharma, B.K., Settypalli, T.B.K., Lamien, C.E., and Dundon, W.G. (2025). Zoonotic Implications of the Co-Circulation of Clade 2.3.4.4b and 2.3.2.1a H5N1 Avian Influenza Viruses in Nepal in 2023. Viruses, 17.","DOI":"10.3390\/v17111481"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e804","DOI":"10.1016\/S2666-5247(22)00232-4","article-title":"The time is now: A call to contain H9N2 avian influenza viruses","volume":"3","author":"Bi","year":"2022","journal-title":"Lancet Microbe"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e01182-19","DOI":"10.1128\/JVI.01182-19","article-title":"Broadly Inhibiting Antineuraminidase Monoclonal Antibodies Induced by Trivalent Influenza Vaccine and H7N9 Infection in Humans","volume":"94","author":"Rijal","year":"2019","journal-title":"J. Virol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.chom.2019.10.003","article-title":"Influenza H7N9 Virus Neuraminidase-Specific Human Monoclonal Antibodies Inhibit Viral Egress and Protect from Lethal Influenza Infection in Mice","volume":"26","author":"Gilchuk","year":"2019","journal-title":"Cell Host Microbe"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"126689","DOI":"10.1016\/j.vaccine.2024.126689","article-title":"Anti-neuraminidase and anti-hemagglutinin stalk responses to different influenza a(H7N9) vaccine regimens","volume":"47","author":"Sahly","year":"2025","journal-title":"Vaccine"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e70097","DOI":"10.1002\/iub.70097","article-title":"Self-Assembled Nanovaccines: A Promising Strategy for Overcoming Influenza Variability and Advancing Universal Vaccine Development","volume":"78","author":"Hsu","year":"2026","journal-title":"IUBMB Life"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/9\/748\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:50:40Z","timestamp":1788241840000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/9\/748"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,28]]},"references-count":86,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["vaccines14090748"],"URL":"https:\/\/doi.org\/10.3390\/vaccines14090748","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,28]]}}}