{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T06:14:19Z","timestamp":1788588859823,"version":"build-2803163510"},"reference-count":81,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T00:00:00Z","timestamp":1639094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012399","name":"Biomedical Advanced Research and Development Authority","doi-asserted-by":"publisher","award":["HHSO100201500033C"],"award-info":[{"award-number":["HHSO100201500033C"]}],"id":[{"id":"10.13039\/100012399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["75N93021C00014"],"award-info":[{"award-number":["75N93021C00014"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Avian influenza viruses from the A\/H5 A\/goose\/Guangdong\/1\/1996 (GsGd) lineage pose a continuing threat to animal and human health. Since their emergence in 1997, these viruses have spread across multiple continents and have become enzootic in poultry. Additionally, over 800 cases of human infection with A\/H5 GsGd viruses have been reported to date, which raises concerns about the potential for a new influenza virus pandemic. The continuous circulation of A\/H5 GsGd viruses for over 20 years has resulted in the genetic and antigenic diversification of their hemagglutinin (HA) surface glycoprotein, which poses a serious challenge to pandemic preparedness and vaccine design. In the present article, clinical studies on A\/H5 influenza vaccination strategies were reviewed to evaluate the breadth of antibody responses induced upon homologous and heterologous prime-boost vaccination strategies. Clinical data on immunological endpoints were extracted from studies and compiled into a dataset, which was used for the visualization and analysis of the height and breadth of humoral immune responses. Several aspects leading to high immunogenicity and\/or cross-reactivity were identified, although the analysis was limited by the heterogeneity in study design and vaccine type used in the included studies. Consequently, crucial questions remain to be addressed in future studies on A\/H5 GsGd vaccination strategies.<\/jats:p>","DOI":"10.3390\/vaccines9121465","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T01:29:33Z","timestamp":1639358973000},"page":"1465","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Cross-Reactivity Conferred by Homologous and Heterologous Prime-Boost A\/H5 Influenza Vaccination Strategies in Humans: A Literature Review"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3635-7952","authenticated-orcid":false,"given":"Adinda","family":"Kok","sequence":"first","affiliation":[{"name":"Department of Viroscience, Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron A. M.","family":"Fouchier","sequence":"additional","affiliation":[{"name":"Department of Viroscience, Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0240-9312","authenticated-orcid":false,"given":"Mathilde","family":"Richard","sequence":"additional","affiliation":[{"name":"Department of Viroscience, Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,10]]},"reference":[{"key":"ref_1","first-page":"951","article-title":"Lessons from Influenza Pandemics of the Last 100 Years","volume":"70","author":"Monto","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Mostafa, A., Abdelwhab, E.M., Mettenleiter, T.C., and Pleschka, S. (2018). Zoonotic Potential of Influenza A Viruses: A Comprehensive Overview. Viruses, 10.","DOI":"10.3390\/v10090497"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1038\/39218","article-title":"A Pandemic Warning?","volume":"389","author":"Claas","year":"1997","journal-title":"Nature"},{"key":"ref_4","unstructured":"WHO (2021, December 07). Cumulative Number of Confirmed Human Cases for Avian Influenza A (H5N1) Reported to WHO, 2003\u20132021. Available online: https:\/\/cdn.who.int\/media\/docs\/default-source\/influenza\/h5n1-human-case-cumulative-table\/2021_may_tableh5n1.pdf?sfvrsn=79ac908a_8&download=true."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1126\/science.1213362","article-title":"Airborne Transmission of Influenza A\/H5N1 Virus between Ferrets","volume":"336","author":"Herfst","year":"2012","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/nature10831","article-title":"Experimental Adaptation of an Influenza H5 HA Confers Respiratory Droplet Transmission to a Reassortant H5 HA\/H1N1 Virus in Ferrets","volume":"486","author":"Imai","year":"2012","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.cell.2014.02.040","article-title":"Identification, Characterization, and Natural Selection of Mutations Driving Airborne Transmission of A\/H5N1 Virus","volume":"157","author":"Linster","year":"2014","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"WHO\/OIE\/FAO H5N1 Evolution Working Group (2008). Toward a Unified Nomenclature System for Highly Pathogenic Avian Influenza Virus (H5N1). Emerg. Infect. Dis., 14, e1.","DOI":"10.3201\/eid1407.071681"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/irv.12324","article-title":"Nomenclature Updates Resulting from the Evolution of Avian Influenza A(H5) Virus Clades 2.1.3.2a, 2.2.1, and 2.3.4 during 2013\u20132014","volume":"9","author":"Smith","year":"2015","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_10","unstructured":"WHO (2021, December 07). Antigenic and Genetic Characteristics of Zoonotic Influenza Viruses and Development of Candidate Vaccine Viruses for Pandemic Preparedness, March 2021. Available online: https:\/\/www.who.int\/influenza\/vaccines\/virus\/202103_zoonotic_vaccinevirusupdate.pdf."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Rockman, S., Laurie, K., and Barr, I. (2020). Pandemic Influenza Vaccines: What Did We Learn from the 2009 Pandemic and Are We Better Prepared Now?. Vaccines, 8.","DOI":"10.3390\/vaccines8020211"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e50830","DOI":"10.1371\/journal.pone.0050830","article-title":"Evaluations for In Vitro Correlates of Immunogenicity of Inactivated Influenza A H5, H7 and H9 Vaccines in Humans","volume":"7","author":"Couch","year":"2012","journal-title":"PLoS ONE"},{"key":"ref_13","unstructured":"(2021, December 07). SAGE Working Group on Influenza Vaccines and Immunizations: Influenza A (H5N1) Vaccine Stockpile and Inter-Pandemic Vaccine Use. Available online: https:\/\/www.who.int\/immunization\/sage\/meetings\/2013\/november\/SAGE_WG_H5vaccine_background_paper_16Oct2013_v4.pdf?ua=1."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"336","DOI":"10.3389\/fimmu.2015.00336","article-title":"B Cells and Functional Antibody Responses to Combat Influenza","volume":"6","author":"Lofano","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_15","unstructured":"WHO (2021, March 28). Tables on Clinical Evaluation of Influenza Vaccines-Pandemic\/Potentially Pandemic Influenza Vaccines. Available online: https:\/\/www.who.int\/immunization\/diseases\/influenza\/clinical_evaluation_tables\/en\/."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1086\/590913","article-title":"An Adjuvanted, Low-Dose, Pandemic Influenza A (H5N1) Vaccine Candidate Is Safe, Immunogenic, and Induces Cross-Reactive Immune Responses in Healthy Adults","volume":"198","author":"Levie","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7428","DOI":"10.1016\/j.vaccine.2009.07.102","article-title":"Immunogenicity and Tolerability of an AS03A-Adjuvanted Prepandemic Influenza Vaccine: A Phase III Study in a Large Population of Asian Adults","volume":"27","author":"Chu","year":"2009","journal-title":"Vaccine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1086\/652701","article-title":"Safety and Cross-Reactive Immunogenicity of Candidate AS03-Adjuvanted Prepandemic H5N1 Influenza Vaccines: A Randomized Controlled Phase 1\/2 Trial in Adults","volume":"201","author":"Langley","year":"2010","journal-title":"J. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Nagai, H., Ikematsu, H., Tenjinbaru, K., Maeda, A., Dram\u00e9, M., and Roman, F.P. (2010). A Phase II, Open-Label, Multicentre Study to Evaluate the Immunogenicity and Safety of an Adjuvanted Prepandemic (H5N1) Influenza Vaccine in Healthy Japanese Adults. BMC Infect. Dis., 10.","DOI":"10.1186\/1471-2334-10-338"},{"key":"ref_20","first-page":"39","article-title":"Cross-Clade Immunogenicity and Safety of an AS03A Adjuvanted Prepandemic H5N1 Influenza Vaccine in Hong Kong","volume":"17","author":"Chu","year":"2011","journal-title":"Hong Kong Med. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1093\/infdis\/jir328","article-title":"Rapid Immunization against H5N1: A Randomized Trial Evaluating Homologous and Cross-Reactive Immune Responses to AS03A-Adjuvanted Vaccination in Adults","volume":"204","author":"Lasko","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_22","first-page":"916","article-title":"Cross-Clade Immunogenicity and Antigen-Sparing with an AS03A-Adjuvanted Prepandemic Influenza Vaccine in a Thai Population","volume":"94","author":"Thongcharoen","year":"2011","journal-title":"J. Med. Assoc. Thail."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.jfma.2011.02.006","article-title":"Safety and Immunogenicity of a Split-Virion AS03 A-Adjuvanted A\/Indonesia\/05\/2005 (H5N1) Vaccine in Taiwanese Adults","volume":"111","author":"Yang","year":"2012","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2800","DOI":"10.1016\/j.vaccine.2015.04.027","article-title":"Immunogenicity and Safety of an AS03-Adjuvanted H5N1 Pandemic Influenza Vaccine in Korean Adults: A Phase IV, Randomized, Open-Label, Controlled Study","volume":"33","author":"Izurieta","year":"2015","journal-title":"Vaccine"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6078","DOI":"10.1016\/j.vaccine.2015.09.022","article-title":"A Clinical Phase I Study of an EB66 Cell-Derived H5N1 Pandemic Vaccine Adjuvanted with AS03","volume":"33","author":"Naruse","year":"2015","journal-title":"Vaccine"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1093\/infdis\/jiv091","article-title":"Immunogenicity and Safety of an EB66 Cell-Culture-Derived Influenza A\/Indonesia\/5\/2005(H5N1) AS03-Adjuvanted Vaccine: A Phase 1 Randomized Trial","volume":"212","author":"Schuind","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1086\/428948","article-title":"Cross-Reactivity to Highly Pathogenic Avian Influenza H5N1 Viruses after Vaccination with Nonadjuvanted and MF59-Adjuvanted Influenza A\/Duck\/Singapore\/97 (H5N3) Vaccine: A Potential Priming Strategy","volume":"191","author":"Stephenson","year":"2005","journal-title":"J. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Banzhoff, A., Gasparini, R., Laghi-Pasini, F., Staniscia, T., Durando, P., Montomoli, E., Capecchi, P.L., Capecchi, P., di Giovanni, P., and Sticchi, L. (2009). MF59-Adjuvanted H5N1 Vaccine Induces Immunologic Memory and Heterotypic Antibody Responses in Non-Elderly and Elderly Adults. PLoS ONE, 4.","DOI":"10.1371\/annotation\/5f2ae0fb-53f1-48c2-aa19-9114765ba029"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1016\/S0149-2918(11)00024-5","article-title":"A Phase III, Randomized, Open-Label Study to Assess the Tolerability and Immunogenicity of an H5N1 Influenza Vaccine Administered to Healthy Adults with a 1-, 2-, 3-, or 6-Week Interval between First and Second Doses","volume":"32","author":"Beran","year":"2010","journal-title":"Clin. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1128\/CVI.00373-12","article-title":"Assessment of Antigen-Specific and Cross-Reactive Antibody Responses to an MF59-Adjuvanted A\/H5N1 Prepandemic Influenza Vaccine in Adult and Elderly Subjects","volume":"19","author":"Bihari","year":"2012","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1016\/j.vaccine.2011.12.009","article-title":"Safety and Immunogenicity of an MF59\u00ae-Adjuvanted A\/H5N1 Pre-Pandemic Influenza Vaccine in Adults and the Elderly","volume":"30","author":"Vesikari","year":"2012","journal-title":"Vaccine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1056\/NEJMoa073121","article-title":"A Clinical Trial of a Whole-Virus H5N1 Vaccine Derived from Cell Culture","volume":"358","author":"Ehrlich","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1086\/597401","article-title":"Immunogenicity, Safety, and Cross-Reactivity of an Inactivated, Adjuvanted, Prototype Pandemic Influenza (H5N1) Vaccine: A Phase II, Double-Blind, Randomized Trial","volume":"48","author":"Wu","year":"2009","journal-title":"Clin. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.vaccine.2011.10.088","article-title":"Safety and Immunogenicity of Two Different Doses of a Vero Cell-Derived, Whole Virus Clade 2 H5N1 (A\/Indonesia\/05\/2005) Influenza Vaccine","volume":"30","author":"Tambyah","year":"2012","journal-title":"Vaccine"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1128\/CVI.00096-13","article-title":"An Inactivated, Adjuvanted Whole Virion Clade 2.2 H5N1 (A\/Chicken\/Astana\/6\/ 05) Influenza Vaccine Is Safe and Immunogenic in a Single Dose in Humans","volume":"20","author":"Sansyzbay","year":"2013","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Landry, N., Ward, B.J., Tr\u00e9panier, S., Montomoli, E., Le Dargis, M., Lapini, G., and V\u00e9zina, L.P. (2010). Preclinical and Clinical Development of Plant-Made Virus-like Particle Vaccine against Avian H5N1 Influenza. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0015559"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/j.1750-2659.2008.00064.x","article-title":"Safety and Immunogenicity of Live Attenuated Influenza Reassortant H5 Vaccine (Phase I-II Clinical Trials)","volume":"2","author":"Rudenko","year":"2008","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_38","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_39","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1016\/S1473-3099(14)70963-6","article-title":"Safety and Immunogenicity of a Modified-Vaccinia-Virus-Ankara-Based Influenza A H5N1 Vaccine: A Randomised, Double-Blind Phase 1\/2a Clinical Trial","volume":"14","author":"Kreijtz","year":"2014","journal-title":"Lancet Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Khurana, S., Coyle, E.M., Manischewitz, J., King, L.R., Ishioka, G., Alexander, J., Smith, J., Gurwith, M., and Golding, H. (2015). Oral Priming with Replicating Adenovirus Serotype 4 Followed by Subunit H5N1 Vaccine Boost Promotes Antibody Affinity Maturation and Expands H5n1 Cross-Clade Neutralization. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0115476"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6284","DOI":"10.1016\/j.vaccine.2009.01.040","article-title":"Single Dose Vaccination with AS03-Adjuvanted H5N1 Vaccines in a Randomized Trial Induces Strong and Broad Immune Responsiveness to Booster Vaccination in Adults","volume":"27","author":"Schwarz","year":"2009","journal-title":"Vaccine"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/j.vaccine.2009.10.017","article-title":"Priming with AS03A-Adjuvanted H5N1 Influenza Vaccine Improves the Kinetics, Magnitude and Durability of the Immune Response after a Heterologous Booster Vaccination: An Open Non-Randomised Extension of a Double-Blind Randomised Primary Study","volume":"28","author":"Roman","year":"2010","journal-title":"Vaccine"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6408","DOI":"10.1016\/j.vaccine.2011.04.072","article-title":"Immunological Priming Induced by a Two-Dose Series of H5N1 Influenza Antigen, Administered Alone or in Combination with Two Different Formulations of AS03 Adjuvant in Adults: Results of a Randomised Single Heterologous Booster Dose Study at 15 Months","volume":"29","author":"Risi","year":"2011","journal-title":"Vaccine"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1750-2659.2012.00349.x","article-title":"An Assessment of Prime-Boost Vaccination Schedules with AS03A-Adjuvanted Prepandemic H5N1 Vaccines: A Randomized Study in European Adults","volume":"7","author":"Gillard","year":"2013","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Gillard, P., Chu, D.W.S., Hwang, S.-J., Yang, P.-C., Thongcharoen, P., Lim, F.S., Dram\u00e9, M., Walravens, K., and Roman, F. (2014). Long-Term Booster Schedules with AS03A-Adjuvanted Heterologous H5N1 Vaccines Induces Rapid and Broad Immune Responses in Asian Adults. BMC Infect. Dis., 14.","DOI":"10.1186\/1471-2334-14-142"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1093\/infdis\/jiv087","article-title":"Safety and Immunogenicity of a Single Low Dose or High Dose of Clade 2 Influenza A(H5N1) Inactivated Vaccine in Adults Previously Primed with Clade 1 Influenza A(H5N1) Vaccine","volume":"212","author":"Winokur","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41541-019-0114-8","article-title":"Heterologous Prime-Boost with A(H5N1) Pandemic Influenza Vaccines Induces Broader Cross-Clade Antibody Responses than Homologous Prime-Boost","volume":"4","author":"Levine","year":"2019","journal-title":"npj Vaccines"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1128\/CVI.00626-12","article-title":"Combined Administration of MF59-Adjuvanted A\/H5N1 Prepandemic and Seasonal Influenza Vaccines: Long-Term Antibody Persistence and Robust Booster Responses 1 Year after a One-Dose Priming Schedule","volume":"20","author":"Lopez","year":"2013","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1001\/jama.2014.12609","article-title":"Immunogenicity of Avian Influenza A\/Anhui\/01\/2005(H5N1) Vaccine with MF59 Adjuvant a Randomized Clinical Trial","volume":"312","author":"Belshe","year":"2014","journal-title":"JAMA-J. Am. Med. Assoc."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"7962","DOI":"10.1073\/pnas.0903181106","article-title":"Fast Rise of Broadly Cross-Reactive Antibodies after Boosting Long-Lived Human Memory B Cells Primed by an MF59 Adjuvanted Prepandemic Vaccine","volume":"106","author":"Galli","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e95496","DOI":"10.1371\/journal.pone.0095496","article-title":"Heterologous Prime-Boost Vaccination with MF59-Adjuvanted H5 Vaccines Promotes Antibody Affinity Maturation towards the Hemagglutinin HA1 Domain and Broad H5N1 Cross-Clade Neutralization","volume":"9","author":"Khurana","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1086\/605608","article-title":"A Cell Culture (Vero)-Derived H5N1 Whole-Virus Vaccine Induces Cross-Reactive Memory Responses","volume":"200","author":"Ehrlich","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1086\/590916","article-title":"Immune Responses of Healthy Subjects to a Single Dose of Intramuscular Inactivated Influenza A\/Vietnam\/1203\/2004 (H5N1) Vaccine after Priming with an Antigenic Variant","volume":"198","author":"Goji","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.vaccine.2020.11.041","article-title":"Long-Lasting Heterologous Antibody Responses after Sequential Vaccination with A\/Indonesia\/5\/2005 and A\/Vietnam\/1203\/2004 Pre-Pandemic Influenza A(H5N1) Virus Vaccines","volume":"39","author":"Haveri","year":"2021","journal-title":"Vaccine"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"707","DOI":"10.3390\/vaccines2040707","article-title":"Overview of Serological Techniques for Influenza Vaccine Evaluation: Past, Present and Future","volume":"2","author":"Trombetta","year":"2014","journal-title":"Vaccines"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1471-2288-10-18","article-title":"Relationship between Haemagglutination-Inhibiting Antibody Titres and Clinical Protection against Influenza: Development and Application of a Bayesian Random-Effects Model","volume":"10","author":"Coudeville","year":"2010","journal-title":"BMC Med. Res. Methodol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"11460","DOI":"10.1038\/s41598-018-29858-w","article-title":"Aluminum Salts as an Adjuvant for Pre-Pandemic Influenza Vaccines: A Meta-Analysis","volume":"8","author":"Lin","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1080\/21645515.2018.1515454","article-title":"Comparative Effectiveness of H7N9 Vaccines in Healthy Individuals","volume":"15","author":"Zheng","year":"2019","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_59","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_60","doi-asserted-by":"crossref","first-page":"e0044921","DOI":"10.1128\/mBio.00449-21","article-title":"Broadly Reactive IgG Responses to Heterologous H5 Prime-Boost Influenza Vaccination Are Shaped by Antigenic Relatedness to Priming Strains","volume":"12","author":"Wang","year":"2021","journal-title":"mBio"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1126\/science.1256427","article-title":"Antibody Landscapes after Influenza Virus Infection or Vaccination","volume":"346","author":"Fonville","year":"2014","journal-title":"Science"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.vaccine.2018.11.064","article-title":"Preclinical Evaluation of the Efficacy of an H5N8 Vaccine Candidate (IDCDC-RG43A) in Mouse and Ferret Models for Pandemic Preparedness","volume":"37","author":"Jeong","year":"2019","journal-title":"Vaccine"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Layton, R.C., Gigliotti, A., Armijo, P., Myers, L., Knight, J., Donart, N., Pyles, J., Vaughan, S., Plourde, J., and Fomukong, N. (2011). Enhanced Immunogenicity, Mortality Protection, and Reduced Viral Brain Invasion by Alum Adjuvant with an H5N1 Split-Virion Vaccine in the Ferret. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020641"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1086\/505225","article-title":"Immunization with Reverse-Genetics\u2013Produced H5N1 Influenza Vaccine Protects Ferrets against Homologous and Heterologous Challenge","volume":"194","author":"Govorkova","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.virol.2016.08.010","article-title":"Cross-Protective Efficacies of Highly-Pathogenic Avian Influenza H5N1 Vaccines against a Recent H5N8 Virus","volume":"498","author":"Park","year":"2016","journal-title":"Virology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.virol.2017.05.010","article-title":"Stockpiled Pre-Pandemic H5N1 Influenza Virus Vaccines with AS03 Adjuvant Provide Cross-Protection from H5N2 Clade 2.3.4.4 Virus Challenge in Ferrets","volume":"508","author":"Sun","year":"2017","journal-title":"Virology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1111\/j.1750-2659.2011.00321.x","article-title":"Efficacy of a Heterologous Vaccine and Adjuvant in Ferrets Challenged with Influenza Virus H5N1","volume":"6","author":"Vela","year":"2012","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"12915","DOI":"10.1073\/pnas.0506416102","article-title":"Role of Specific Hemagglutinin Amino Acids in the Immunogenicity and Protection of H5N1 Influenza Virus Vaccines","volume":"102","author":"Hoffmann","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1086\/507709","article-title":"Cross-Protectiveness and Immunogenicity of Influenza A\/Duck\/Singapore\/3\/97(H5) Vaccines against Infection with A\/Vietnam\/1203\/04(H5N1) Virus in Ferrets","volume":"194","author":"Lipatov","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2165\/00044011-199815010-00001","article-title":"Comparison of Serology and Reactogenicity between Influenza Subunit Vaccines and Whole Virus or Split Vaccines. A Review and Meta-Analysis of the Literature","volume":"15","author":"Beyer","year":"1998","journal-title":"Clin. Drug Investig."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"4160","DOI":"10.1016\/j.vaccine.2008.05.077","article-title":"Phase I and II Randomised Trials of the Safety and Immunogenicity of a Prototype Adjuvanted Inactivated Split-Virus Influenza A (H5N1) Vaccine in Healthy Adults","volume":"26","author":"Nolan","year":"2008","journal-title":"Vaccine"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1128\/CVI.00327-08","article-title":"Cross-Reactive Immunity to Clade 2 Strains of Influenza Virus A Subtype H5N1 Induced in Adults and Elderly Patients by Fluval, a Prototype Pandemic Influenza Virus Vaccine Derived by Reverse Genetics, Formulated with a Phosphate Adjuvant, and Directed to Clade 1 Strains","volume":"16","author":"Fazekas","year":"2009","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.vaccine.2018.11.069","article-title":"Safety and Immunogenicity of Influenza A(H5N1) Vaccine Stored up to Twelve Years in the National Pre-Pandemic Influenza Vaccine Stockpile (NPIVS)","volume":"37","author":"Oshansky","year":"2019","journal-title":"Vaccine"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"11756","DOI":"10.1128\/JVI.01460-06","article-title":"Cellular Immune Responses in Children and Adults Receiving Inactivated or Live Attenuated Influenza Vaccines","volume":"80","author":"He","year":"2006","journal-title":"J. Virol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s41541-021-00292-w","article-title":"SARS-CoV-2 Vaccines Strategies: A Comprehensive Review of Phase 3 Candidates","volume":"6","author":"Kyriakidis","year":"2021","journal-title":"npj Vaccines"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1586\/14760584.2014.922416","article-title":"Improving Pandemic H5N1 Influenza Vaccines by Combining Different Vaccine Platforms","volume":"13","author":"Luke","year":"2014","journal-title":"Expert Rev. Vaccines"},{"key":"ref_77","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_78","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1111\/irv.12706","article-title":"Meeting Report and Review: Immunological Assays and Correlates of Protection for next-Generation Influenza Vaccines","volume":"14","author":"Krammer","year":"2020","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3326","DOI":"10.1016\/j.vaccine.2019.04.074","article-title":"MRNA Vaccines against H10N8 and H7N9 Influenza Viruses of Pandemic Potential Are Immunogenic and Well Tolerated in Healthy Adults in Phase 1 Randomized Clinical Trials","volume":"37","author":"Feldman","year":"2019","journal-title":"Vaccine"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1038\/nbt.2436","article-title":"Protective Efficacy of in Vitro Synthesized, Specific MRNA Vaccines against Influenza A Virus Infection","volume":"30","author":"Petsch","year":"2012","journal-title":"Nat. Biotechnol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.coviro.2016.12.004","article-title":"Immune History and Influenza Virus Susceptibility","volume":"22","author":"Cobey","year":"2017","journal-title":"Curr. Opin. Virol."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/9\/12\/1465\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:45:16Z","timestamp":1760168716000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/9\/12\/1465"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,10]]},"references-count":81,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["vaccines9121465"],"URL":"https:\/\/doi.org\/10.3390\/vaccines9121465","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,10]]}}}