{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:08:04Z","timestamp":1788930484355,"version":"build-2803163510"},"reference-count":105,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007108","name":"George Washington University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007108","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/00y4zzh67","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R42 AI155275"],"award-info":[{"award-number":["R42 AI155275"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"award":["R42 AI155275"],"award-info":[{"award-number":["R42 AI155275"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"name":"NIH","award":["P51OD011106"],"award-info":[{"award-number":["P51OD011106"]}]},{"name":"NIH","award":["UC7AI180311"],"award-info":[{"award-number":["UC7AI180311"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Highly pathogenic avian influenza (HPAI) represents an enormous pandemic risk amid the ongoing H5N1 panzootic. HPAI, defined by its high lethality in domestic poultry, includes the influenza A virus (IAV) H5N1 and H7N9 subtypes and has a 40\u201350% case fatality rate in humans. To facilitate the development of efficacious HPAI vaccination regimens and isolation of HPAI-neutralizing monoclonal antibodies (nmAbs) for prophylactic and therapeutic use, we performed a proof-of-concept pilot study wherein we developed an array of mRNA and adenovirus-vectored vaccines encoding HPAI hemagglutinins (HAs) and then assessed their immunogenicity in IAV-na\u00efve Indian rhesus macaques (RMs). All RMs developed binding IgG recognizing both HPAI HAs. HPAI-nAbs were detected in RMs vaccinated with full-length HAs, but not in RMs vaccinated with HA stems alone. Potent HPAI neutralization activity was observed in two animals with serum ID50 titers of ~1:100,000 against H5N1 and ~1:50,000 against H7N9. Most RMs developed cross-reactive IgG recognizing the HAs of additional IAV subtypes, and HA-specific B cells were readily identifiable in vaccinee PBMCs by flow cytometric analysis. The results of our pilot study suggest that elicitation of potent HPAI-nAb responses is enhanced by vaccination with the HA head domain and that vaccination with the HA stem alone tends to elicit binding non-nAbs. Furthermore, use of our fluorophore-conjugated HA probes to identify HA-specific B cells could enable HPAI-nmAb isolation. Collectively, our findings could facilitate the development of novel vaccines and nmAb therapeutics leveraging the superior neutralization potency of HA head-specific Abs to prevent and treat HPAI infections in humans.<\/jats:p>","DOI":"10.3390\/v18090981","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T16:30:02Z","timestamp":1788798602000},"page":"981","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Elicitation of Potent H5N1- and H7N9-Neutralizing Antibody Responses in Rhesus Macaques by Sequential Heterologous Vaccination with mRNA and Adenoviral Vectors Encoding Full-Length Hemagglutinins"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4943-3494","authenticated-orcid":false,"given":"Brandon C.","family":"Rosen","sequence":"first","affiliation":[{"name":"Department of Pathology, George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA"},{"name":"Medical Scientist Training Program, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3192-3483","authenticated-orcid":false,"given":"Jack T.","family":"Mauter","sequence":"additional","affiliation":[{"name":"Department of Pathology, George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2217-897X","authenticated-orcid":false,"given":"Thomas B.","family":"Voigt","sequence":"additional","affiliation":[{"name":"Department of Pathology, George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovana","family":"de Figueiredo Godoy","sequence":"additional","affiliation":[{"name":"Department of Pathology, George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6867-211X","authenticated-orcid":false,"given":"Emma L.","family":"Walker","sequence":"additional","affiliation":[{"name":"Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 15261, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan J.","family":"Louw","sequence":"additional","affiliation":[{"name":"Department of Pathology, George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noor","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Pathology, George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Christakis","family":"Panayiotou","sequence":"additional","affiliation":[{"name":"Department of Pathology, George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Aaron","family":"Yrizarry-Medina","sequence":"additional","affiliation":[{"name":"Department of Pathology, George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Joshua","family":"Terao","sequence":"additional","affiliation":[{"name":"Department of Pathology, George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8197-5309","authenticated-orcid":false,"given":"Eva G.","family":"Rakasz","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1484-6408","authenticated-orcid":false,"given":"Matthew R.","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn M.","family":"Dudley","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0076-9023","authenticated-orcid":false,"given":"Douglas S.","family":"Reed","sequence":"additional","affiliation":[{"name":"Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 15261, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David I.","family":"Watkins","sequence":"additional","affiliation":[{"name":"Department of Pathology, George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA"},{"name":"Mabloc, LLC, 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Transl. Med."},{"key":"ref_2","unstructured":"United Nations (2026, September 01). Avian Flu Reported in 108 Countries Across Five Continents, Says UN Health Agency. Available online: https:\/\/news.un.org\/en\/story\/2024\/12\/1158286."},{"key":"ref_3","first-page":"2300001","article-title":"Highly pathogenic avian influenza A(H5N1) virus infection in farmed minks, Spain, October 2022","volume":"28","author":"Monne","year":"2023","journal-title":"Euro Surveill."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/01652176.2023.2265173","article-title":"Mass mortality event in South American sea lions (Otaria flavescens) correlated to highly pathogenic avian influenza (HPAI) H5N1 outbreak in Chile","volume":"43","author":"Ulloa","year":"2023","journal-title":"Vet. Q."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5489","DOI":"10.1038\/s41467-023-41182-0","article-title":"Highly pathogenic avian influenza A (H5N1) in marine mammals and seabirds in Peru","volume":"14","author":"Leguia","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/s41586-024-07849-4","article-title":"Spillover of highly pathogenic avian influenza H5N1 virus to dairy cattle","volume":"634","author":"Caserta","year":"2024","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/s41586-024-07766-6","article-title":"Pathogenicity and transmissibility of bovine H5N1 influenza virus","volume":"633","author":"Eisfeld","year":"2024","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1126\/science.adt0180","article-title":"A single mutation in bovine influenza H5N1 hemagglutinin switches specificity to human receptors","volume":"386","author":"Lin","year":"2024","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"002109","DOI":"10.1099\/jgv.0.002109","article-title":"H5N1 2.3.4.4b: A review of mammalian adaptations and risk of pandemic emergence","volume":"106","author":"Capelastegui","year":"2025","journal-title":"J. Gen. Virol."},{"key":"ref_10","unstructured":"American Academy of Ophthalmology (2025, December 23). Novel H5N1 Bird Flu Outbreak. Available online: https:\/\/www.aao.org\/education\/clinical-statement\/novel-h5n1-bird-flu-outbreak-1."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1056\/NEJMoa2414610","article-title":"Highly Pathogenic Avian Influenza A(H5N1) Virus Infections in Humans","volume":"392","author":"Garg","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_12","first-page":"477","article-title":"Influenza A(H5N1) Immune Response among Ferrets with Influenza A(H1N1)pdm09 Immunity","volume":"31","author":"Werner","year":"2025","journal-title":"Emerg. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1126\/science.aag1322","article-title":"Potent protection against H5N1 and H7N9 influenza via childhood hemagglutinin imprinting","volume":"354","author":"Gostic","year":"2016","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Nu\u00f1ez, I.A., Jang, H., Huang, Y., Kelvin, A., and Ross, T.M. (2023). Influenza virus immune imprinting dictates the clinical outcomes in ferrets challenged with highly pathogenic avian influenza virus H5N1. Front. Vet. Sci., 10.","DOI":"10.3389\/fvets.2023.1286758"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/s41586-024-08254-7","article-title":"A human isolate of bovine H5N1 is transmissible and lethal in animal models","volume":"636","author":"Gu","year":"2024","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1038\/s41586-025-08609-8","article-title":"Pathogenesis of bovine H5N1 clade 2.3.4.4b infection in macaques","volume":"640","author":"Rosenke","year":"2025","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1126\/science.1244730","article-title":"Substitutions Near the Receptor Binding Site Determine Major Antigenic Change During Influenza Virus Evolution","volume":"342","author":"Koel","year":"2013","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1038\/ni.3680","article-title":"Defining B cell immunodominance to viruses","volume":"18","author":"Angeletti","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"10432","DOI":"10.1038\/s41598-018-28706-1","article-title":"The influenza virus hemagglutinin head evolves faster than the stalk domain","volume":"8","author":"Kirkpatrick","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.it.2018.04.008","article-title":"Understanding and Manipulating Viral Immunity: Antibody Immunodominance Enters Center Stage","volume":"39","author":"Angeletti","year":"2018","journal-title":"Trends Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/s41541-018-0076-2","article-title":"AS03-adjuvanted H5N1 vaccine promotes antibody diversity and affinity maturation, NAI titers, cross-clade H5N1 neutralization, but not H1N1 cross-subtype neutralization","volume":"3","author":"Khurana","year":"2018","journal-title":"NPJ Vaccines"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"17957","DOI":"10.1073\/pnas.1906613117","article-title":"Adjuvanted H5N1 influenza vaccine enhances both cross-reactive memory B cell and strain-specific naive B cell responses in humans","volume":"117","author":"Ellebedy","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2193119","DOI":"10.1080\/21645515.2023.2193119","article-title":"Antibody responses against heterologous H5N1 strains for an MF59-adjuvanted cell culture\u2013derived H5N1 (aH5n1c) influenza vaccine in adults and older adults","volume":"19","author":"Frey","year":"2023","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_24","unstructured":"Enserink, M. (2026, September 01). More Tamiflu Resistance in Bird Flu. Sci News, Available online: https:\/\/www.science.org\/content\/article\/more-tamiflu-resistance-bird-flu."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1056\/NEJMp0900648","article-title":"Global transmission of oseltamivir-resistant influenza","volume":"360","author":"Moscona","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1086\/656317","article-title":"Has oseltamivir been shown to be effective for treatment of H5N1 influenza?","volume":"202","author":"Couch","year":"2010","journal-title":"J. Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1038\/aps.2013.121","article-title":"Characteristics of human infection with avian influenza viruses and development of new antiviral agents","volume":"34","author":"Liu","year":"2013","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"949","DOI":"10.3201\/eid2206.151037","article-title":"Debate regarding oseltamivir use for seasonal and pandemic influenza","volume":"22","author":"Hurt","year":"2016","journal-title":"Emerg. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Parra-Rojas, C., Nguyen, V.K., Hernandez-Mejia, G., and Hernandez-Vargas, E.A. (2018). Neuraminidase inhibitors in influenza treatment and prevention\u2013Is it time to call it a day?. Viruses, 10.","DOI":"10.3390\/v10090454"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.antiviral.2018.08.007","article-title":"Neuraminidase inhibitor susceptibility profiles of highly pathogenic influenza A (H5N1) viruses isolated from avian species in India (2006\u20132015)","volume":"158","author":"Sood","year":"2018","journal-title":"Antivir. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s12985-019-1194-9","article-title":"Highly pathogenic avian influenza H7N9 viruses with reduced susceptibility to neuraminidase inhibitors showed comparable replication capacity to their sensitive counterparts","volume":"16","author":"Tang","year":"2019","journal-title":"Virol. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3116","DOI":"10.1038\/s41598-020-60068-5","article-title":"Assessment of adverse events related to anti-influenza neuraminidase inhibitors using the FDA adverse event reporting system and online patient reviews","volume":"10","author":"Han","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.ijid.2020.12.028","article-title":"Effectiveness of neuraminidase inhibitors to prevent mortality in patients with laboratory-confirmed avian influenza A H7N9","volume":"103","author":"Cheng","year":"2021","journal-title":"Int. J. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1093\/infdis\/jiad418","article-title":"Antiviral Susceptibility of Highly Pathogenic Avian Influenza A(H5N1) Viruses Circulating Globally in 2022\u20132023","volume":"229","author":"Andreev","year":"2024","journal-title":"J. Infect. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e01626-18","DOI":"10.1128\/JVI.01626-18","article-title":"The frequency of vaccine-induced T-cell responses does not predict the rate of acquisition after repeated intrarectal SIVmac239 challenges in Mamu-B*08+ rhesus macaques","volume":"93","author":"Martins","year":"2019","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Pedre\u00f1o-Lopez, N., Rosen, B.C., Flores, W.J., Gorman, M.J., Voigt, T.B., Ricciardi, M.J., Crosno, K., Weisgrau, K.L., Parks, C.L., and Lifson, J.D. (2021). Non-neutralizing Antibodies May Contribute to Suppression of SIVmac239 Viremia in Indian Rhesus Macaques. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.657424"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Rosen, B.C., Sawatzki, K., Ricciardi, M.J., Smith, E., Golez, I., Mauter, J.T., Pedre\u00f1o-L\u00f3pez, N., Yrizarry-Medina, A., Weisgrau, K.L., and Vosler, L.J. (2024). Acute-phase innate immune responses in SIVmac239-infected Mamu-B*08+ Indian rhesus macaques may contribute to the establishment of elite control. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1478063"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1097\/QAI.0000000000001079","article-title":"Effects of Well-Controlled HIV Infection on Complement Activation and Function","volume":"73","author":"Rossheim","year":"2016","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_39","unstructured":"World Economic Forum, and World Health Organization (2026, September 01). Fighting COVID-19 Could Cost 500 Times as Much as Pandemic Prevention Measures. Available online: https:\/\/extranet.who.int\/sph\/fighting-covid-19-could-cost-500-times-much-pandemic-prevention-measures."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zhou, F., Hansen, L., Pedersen, G., Gr\u00f8deland, G., and Cox, R. (2021). Matrix M Adjuvanted H5N1 Vaccine Elicits Broadly Neutralizing Antibodies and Neuraminidase Inhibiting Antibodies in Humans That Correlate with In Vivo Protection. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.747774"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.cell.2016.06.043","article-title":"Vaccine-Induced Antibodies that Neutralize Group 1 and Group 2 Influenza A Viruses","volume":"166","author":"Joyce","year":"2016","journal-title":"Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e140794","DOI":"10.1172\/JCI140794","article-title":"A replication-competent adenovirus-vectored influenza vaccine induces durable systemic and mucosal immunity","volume":"131","author":"Matsuda","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.jmii.2019.03.009","article-title":"The safety and immunogenicity of a cell-derived adjuvanted H5N1 vaccine\u2014A phase I randomized clinical trial","volume":"52","author":"Cheng","year":"2019","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1093\/infdis\/jiy214","article-title":"Induction of cross-clade antibody and T-Cell responses by a modified vaccinia virus Ankara-based influenza A(H5N1) vaccine in a randomized phase 1\/2a Clinical Trial","volume":"218","author":"Altenburg","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1093\/infdis\/jiu359","article-title":"Heterologous prime-boost vaccination using an AS03B-adjuvanted influenza A(H5N1) vaccine in infants and children < 3 years of age","volume":"210","author":"Nolan","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e35","DOI":"10.1097\/INF.0000000000000968","article-title":"Assessment of Prime-boost Vaccination Using an AS03B-adjuvanted Influenza A (H5N1) Vaccine: A Randomized Trial in Children of Three to Less Than Eighteen Years of Age","volume":"35","author":"Izurieta","year":"2016","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1093\/infdis\/jit180","article-title":"Prime-boost interval matters: A randomized phase 1 study to identify the minimum interval necessary to observe the h5 dna influenza vaccine priming effect","volume":"208","author":"Ledgerwood","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/S1473-3099(17)30240-2","article-title":"Safety and immunogenicity of a live attenuated influenza H5 candidate vaccine strain A\/17\/turkey\/Turkey\/05\/133 H5N2 and its priming effects for potential pre-pandemic use: A randomised, double-blind, placebo-controlled trial","volume":"17","author":"Pitisuttithum","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e01970-17","DOI":"10.1128\/JVI.01970-17","article-title":"Intranasal Live Influenza Vaccine Priming Elicits Localized B Cell Responses in Mediastinal Lymph Nodes","volume":"92","author":"Jegaskanda","year":"2018","journal-title":"J. Virol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1111\/1348-0421.12775","article-title":"Human immune responses elicited by an intranasal inactivated H5 influenza vaccine","volume":"64","author":"Ainai","year":"2020","journal-title":"Microbiol. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5449","DOI":"10.1016\/j.vaccine.2016.08.055","article-title":"Clinical testing of an inactivated influenza A\/H5N1 vaccine candidate in a double-blinded, placebo-controlled, randomized trial in healthy adults in Vietnam","volume":"34","author":"Phan","year":"2016","journal-title":"Vaccine"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1093\/infdis\/jiad276","article-title":"Safety and Immunogenicity of a Delayed Heterologous Avian Influenza A(H7N9) Vaccine Boost Following Different Priming Regimens: A Randomized Clinical Trial","volume":"229","author":"Yildirim","year":"2024","journal-title":"J. Infect. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1001\/jama.2014.12854","article-title":"Serological responses to an avian influenza A\/H7N9 vaccine mixed at the point-of-use with MF59 adjuvant a randomized clinical trial","volume":"312","author":"Mulligan","year":"2014","journal-title":"J. Am. Med. Assoc."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"8049","DOI":"10.1016\/j.vaccine.2011.08.042","article-title":"Evaluation of a virosomal H5N1 vaccine formulated with Matrix MTM adjuvant in a phase I clinical trial","volume":"29","author":"Cox","year":"2011","journal-title":"Vaccine"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1016\/S1473-3099(11)70240-7","article-title":"DNA priming and influenza vaccine immunogenicity: Two phase 1 open label randomised clinical trials","volume":"11","author":"Ledgerwood","year":"2011","journal-title":"Lancet Infect. Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1093\/cid\/ciae173","article-title":"A Phase 2 Clinical Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of Different Prime-Boost Vaccination Schedules of 2013 and 2017 A(H7N9) Inactivated Influenza Virus Vaccines Administered With and Without AS03 Adjuvant in Healthy US Adults","volume":"78","author":"Rostad","year":"2024","journal-title":"Clin. Infect. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"126702","DOI":"10.1016\/j.vaccine.2024.126702","article-title":"Safety and immunogenicity of ascending doses of influenza A(H7N9) inactivated vaccine with or without MF59\u00ae","volume":"47","author":"Frey","year":"2025","journal-title":"Vaccine"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/S1473-3099(15)00378-3","article-title":"H7N9 live attenuated influenza vaccine in healthy adults: A randomised, double-blind, placebo-controlled, phase 1 trial","volume":"16","author":"Rudenko","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1128\/CVI.00272-14","article-title":"An H7N1 influenza virus vaccine induces broadly reactive antibody responses against H7N9 in humans","volume":"21","author":"Krammer","year":"2014","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1016\/j.ymthe.2017.03.035","article-title":"Preclinical and Clinical Demonstration of Immunogenicity by mRNA Vaccines against H10N8 and H7N9 Influenza Viruses","volume":"25","author":"Bahl","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"104776","DOI":"10.1016\/j.antiviral.2020.104776","article-title":"Evaluation of the immune response of a H7N9 candidate vaccine virus derived from the fifth wave A\/Guangdong\/17SF003\/2016","volume":"177","author":"Dong","year":"2020","journal-title":"Antivir. Res."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Fan, S., Gao, Y., Shinya, K., Li, C.K., Li, Y., Shi, J., Jiang, Y., Suo, Y., Tong, T., and Zhong, G. (2009). Immunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000409"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Nakayama, M., Shichinohe, S., Itoh, Y., Ishigaki, H., Kitano, M., Arikata, M., Pham, V.L., Ishida, H., Kitagawa, N., and Okamatsu, M. (2013). Protection against H5N1 highly pathogenic avian and pandemic (H1N1) 2009 influenza virus infection in cynomolgus monkeys by an inactivated H5N1 whole particle vaccine. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082740"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e01321-21","DOI":"10.1128\/JVI.01321-21","article-title":"Evaluation of a New Viral Vaccine Vector in Mice and Rhesus Macaques: J Paramyxovirus Expressing Hemagglutinin of Influenza A Virus H5N1","volume":"95","author":"Abraham","year":"2021","journal-title":"J. Virol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4602","DOI":"10.1128\/JVI.02491-10","article-title":"Vesicular Stomatitis Virus-Based H5N1 Avian Influenza Vaccines Induce Potent Cross-Clade Neutralizing Antibodies in Rhesus Macaques","volume":"85","author":"Schwartz","year":"2011","journal-title":"J. Virol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"8139","DOI":"10.1128\/JVI.00425-14","article-title":"African Green Monkeys Recapitulate the Clinical Experience with Replication of Live Attenuated Pandemic Influenza Virus Vaccine Candidates","volume":"88","author":"Matsuoka","year":"2014","journal-title":"J. Virol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/j.vaccine.2017.01.008","article-title":"Potential risk of repeated nasal vaccination that induces allergic reaction with mucosal IgE and airway eosinophilic infiltration in cynomolgus macaques infected with H5N1 highly pathogenic avian influenza virus","volume":"35","author":"Nakayama","year":"2017","journal-title":"Vaccine"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.antiviral.2014.04.003","article-title":"Induction of neutralizing antibodies to influenza A virus H7N9 by inactivated whole virus in mice and nonhuman primates","volume":"107","author":"Pan","year":"2014","journal-title":"Antivir. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0167-5699(00)01612-1","article-title":"The prime-boost strategy: Exciting prospects for improved vaccination","volume":"21","author":"Ramshaw","year":"2000","journal-title":"Trends Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.it.2003.11.009","article-title":"Jump-starting the immune system: Prime-boosting comes of age","volume":"25","author":"Woodland","year":"2004","journal-title":"Trends Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"15556","DOI":"10.1128\/JVI.79.24.15556-15566.2005","article-title":"Cytotoxic T-Lymphocyte Escape Does Not Always Explain the Transient Control of Simian Immunodeficiency Virus SIVmac239 Viremia in Adenovirus-Boosted and DNA-Primed Mamu-A*01-Positive Rhesus Macaques","volume":"79","author":"McDermott","year":"2005","journal-title":"J. Virol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"15547","DOI":"10.1128\/JVI.79.24.15547-15555.2005","article-title":"Attenuation of Simian Immunodeficiency Virus SIVmac239 Infection by Prophylactic Immunization with DNA and Recombinant Adenoviral Vaccine Vectors Expressing Gag","volume":"79","author":"Casimiro","year":"2005","journal-title":"J. Virol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nature07469","article-title":"Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys","volume":"457","author":"Liu","year":"2009","journal-title":"Nature"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1001\/jama.2016.4218","article-title":"Safety and immunogenicity of novel adenovirus type 26-and modified vaccinia Ankara-vectored Ebola vaccines: A randomized clinical trial","volume":"315","author":"Milligan","year":"2016","journal-title":"J. Am. Med. Assoc."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Palgen, J.-L., Feraoun, Y., Dzangu\u00e9-Tchoupou, G., Joly, C., Martinon, F., Le Grand, R., and Beignon, A.S. (2021). Optimize Prime\/Boost Vaccine Strategies: Trained Immunity as a New Player in the Game. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.612747"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1038\/s41598-024-84392-2","article-title":"Serological insights from SARS-CoV-2 heterologous prime and boost responses in Thailand","volume":"15","author":"Ward","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1097\/QAI.0000000000000359","article-title":"Antiretroviral therapy in HIV-infected elite controllers: Impact on gut immunology, microbial translocation, and biomarkers of serious non-AIDS conditions","volume":"67","author":"Kim","year":"2014","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Okulicz, J.F., Mesner, O., Ganesan, A., O\u2019Bryan, T.A., Deiss, R.G., and Agan, B.K. (2014). Hepatitis B vaccine responsiveness and clinical outcomes in HIV controllers. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0105591"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1093\/cid\/ciz442","article-title":"Antiretroviral therapy reduces T-cell activation and immune exhaustion markers in human immunodeficiency virus controllers","volume":"70","author":"Li","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"O\u2019Connor, M.A., Erasmus, J.H., Randall, S., Archer, J., Lewis, T.B., Brown, B., Fredericks, M., Groenier, S., Iwayama, N., and Ahrens, C. (2021). A single dose SARS-CoV-2 replicon RNA vaccine induces cellular and humoral immune responses in simian immunodeficiency virus infected and uninfected pigtail macaques. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.800723"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"316ra192","DOI":"10.1126\/scitranslmed.aad0522","article-title":"Immune history profoundly affects broadly protective B cell responses to influenza","volume":"7","author":"Andrews","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.it.2017.08.003","article-title":"From Original Antigenic Sin to the Universal Influenza Virus Vaccine","volume":"39","author":"Henry","year":"2018","journal-title":"Trends Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"335","DOI":"10.4049\/jimmunol.1801149","article-title":"Original Antigenic Sin: How First Exposure Shapes Lifelong Anti\u2013Influenza Virus Immune Responses","volume":"202","author":"Zhang","year":"2019","journal-title":"J. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"17221","DOI":"10.1073\/pnas.1920321117","article-title":"Original antigenic sin priming of influenza virus hemagglutinin stalk antibodies","volume":"117","author":"Arevalo","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"100509","DOI":"10.1016\/j.xcrm.2022.100509","article-title":"Inactivated and live-attenuated seasonal influenza vaccines boost broadly neutralizing antibodies in children","volume":"3","author":"Yegorov","year":"2022","journal-title":"Cell Rep. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.coviro.2013.07.007","article-title":"Influenza virus hemagglutinin stalk-based antibodies and vaccines","volume":"3","author":"Krammer","year":"2013","journal-title":"Curr. Opin. Virol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3159","DOI":"10.3390\/v6083159","article-title":"Options and obstacles for designing a universal influenza vaccine","volume":"6","author":"Jang","year":"2014","journal-title":"Viruses"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/nm.3443","article-title":"Broadly neutralizing hemagglutinin stalk-specific antibodies require FcR interactions for protection against influenza virus in vivo","volume":"20","author":"Dilillo","year":"2014","journal-title":"Nat. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1126\/science.1171491","article-title":"Antibody recognition of a highly conserved influenza virus epitope","volume":"324","author":"Ekiert","year":"2009","journal-title":"Science"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/nsmb.1566","article-title":"Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses","volume":"16","author":"Sui","year":"2009","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"200ra114","DOI":"10.1126\/scitranslmed.3006366","article-title":"Vaccine-Induced Anti-HA2 Antibodies Promote Virus Fusion and Enhance Influenza Virus Respiratory Disease","volume":"5","author":"Khurana","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1126\/science.1204839","article-title":"A highly conserved neutralizing epitope on group 2 influenza A viruses","volume":"333","author":"Ekiert","year":"2011","journal-title":"Science"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1126\/science.1205669","article-title":"A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins","volume":"333","author":"Corti","year":"2011","journal-title":"Science"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.cell.2016.05.073","article-title":"Structure and Function Analysis of an Antibody Recognizing All Influenza A Subtypes","volume":"166","author":"Kallewaard","year":"2016","journal-title":"Cell"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"eaan2676","DOI":"10.1126\/sciimmunol.aan2676","article-title":"Preferential induction of cross-group influenza A hemagglutinin stem-specific memory B cells after H7N9 immunization in humans","volume":"2","author":"Andrews","year":"2017","journal-title":"Sci. Immunol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1128\/CVI.00081-12","article-title":"High titer and avidity of nonneutralizing antibodies against influenza vaccine antigen are associated with severe influenza","volume":"19","author":"To","year":"2012","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.1016\/j.immuni.2022.10.015","article-title":"Co-immunization with hemagglutinin stem immunogens elicits cross-group neutralizing antibodies and broad protection against influenza A viruses","volume":"55","author":"Moin","year":"2022","journal-title":"Immunity"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1126\/science.ado6481","article-title":"Pre-exposure antibody prophylaxis protects macaques from severe influenza","volume":"387","author":"Kanekiyo","year":"2025","journal-title":"Science"},{"key":"ref_99","unstructured":"Weatherall, D.J. (2020, May 01). The Use of Non-Human Primates in Research. Available online: https:\/\/mrc.ukri.org\/documents\/pdf\/the-use-of-non-human-primates-in-research\/."},{"key":"ref_100","unstructured":"National Research Council of the National Academies (2011). Guide for the Care and Use of Laboratory Animals, The National Academies Press. [8th ed.]."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"10802","DOI":"10.1128\/JVI.01440-15","article-title":"Vaccine-induced simian immunodeficiency virus-specific CD8+ T-cell responses focused on a single Nef epitope select for escape variants shortly after infection","volume":"89","author":"Martins","year":"2015","journal-title":"J. Virol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e00690-18","DOI":"10.1128\/JVI.00690-18","article-title":"Mamu-B*17+ rhesus macaques vaccinated with env, vif, and nef manifest early control of SIVmac239 replication","volume":"92","author":"Martins","year":"2018","journal-title":"J. Virol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e02810-18","DOI":"10.1128\/mBio.02810-18","article-title":"Design of Nanoparticulate Group 2 Influenza Virus Hemagglutinin Stem Antigens That Activate Unmutated Ancestor B Cell Receptors of Broadly Neutralizing Antibody Lineages","volume":"10","author":"Corbett","year":"2019","journal-title":"mBio"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"107830","DOI":"10.1016\/j.isci.2023.107830","article-title":"Refined semi-lethal aerosol H5N1 influenza model in cynomolgus macaques for evaluation of medical countermeasures","volume":"26","author":"Kanekiyo","year":"2023","journal-title":"iScience"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"25440","DOI":"10.1021\/acsomega.0c03990","article-title":"Mammalian Expression and in Situ Biotinylation of Extracellular Protein Targets for Directed Evolution","volume":"5","author":"Grindel","year":"2020","journal-title":"ACS Omega"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/9\/981\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:27:03Z","timestamp":1788928023000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/9\/981"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,7]]},"references-count":105,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["v18090981"],"URL":"https:\/\/doi.org\/10.3390\/v18090981","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,7]]}}}