{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T23:20:36Z","timestamp":1785799236935,"version":"3.56.0"},"reference-count":23,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T00:00:00Z","timestamp":1604534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>After the influenza H1N1 pandemic of 2009, the seasonal A\/Brisbane\/59\/2007 strain was replaced by the A\/California\/07\/2009 strain for the influenza virus vaccine composition. After several seasons with no indications on the occurrence of antigenic drift, A\/Michigan\/45\/2015 was chosen as the H1N1 vaccine strain for the 2017\/2018 season. Since the immune response to influenza is shaped by the history of exposure to antigenically similar strains, the potential cross-protection between seasonal human influenza vaccine strains and the emerging pandemic strains was investigated. Human serum samples were tested by hemagglutination inhibition and single radial hemolysis assays against A\/Brisbane\/59\/2007, A\/California\/07\/2009, and A\/Michigan\/45\/2015 strains. Strong cross-reactions between A\/California\/07\/2009 and A\/Michigan\/45\/2015 strains were observed in 2009\/2010, most likely induced by the start of the 2009 pandemic, and the subsequent post-pandemic seasons from 2010\/2011 onward when A\/California\/07\/2009 became the predominant strain. In the 2014\/2015 season, population immunity against A\/California\/07\/2009 and A\/Michigan\/45\/2015 strains increased again, associated with strong cross-reactions. Whereas hemagglutination inhibition assay has a higher sensitivity for detection of new seasonal drift, the single radial hemolysis assay is an excellent tool for determining the presence of pre-existing immunity, allowing a potential prediction on the booster potential of influenza vaccines against newly emerging drifted strains.<\/jats:p>","DOI":"10.3390\/vaccines8040656","type":"journal-article","created":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T09:04:34Z","timestamp":1604567074000},"page":"656","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Serologically-Based Evaluation of Cross-Protection Antibody Responses among Different A(H1N1) Influenza Strains"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6817-2461","authenticated-orcid":false,"given":"Serena","family":"Marchi","sequence":"first","affiliation":[{"name":"Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5877-3095","authenticated-orcid":false,"given":"Ilaria","family":"Manini","sequence":"additional","affiliation":[{"name":"Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy"},{"name":"Interuniversity Research Center on Influenza and Other Transmissible Infections (CIRI-IT), 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otfried","family":"Kistner","sequence":"additional","affiliation":[{"name":"VisMederi srl, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7504-1822","authenticated-orcid":false,"given":"Pietro","family":"Piu","sequence":"additional","affiliation":[{"name":"VisMederi srl, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmond J.","family":"Remarque","sequence":"additional","affiliation":[{"name":"Department of Virology, Biomedical Primate Research Centre, 2288 Rijswijk, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Manenti","sequence":"additional","affiliation":[{"name":"VisMederi srl, 53100 Siena, Italy"},{"name":"VisMederi Research srl, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Biuso","sequence":"additional","affiliation":[{"name":"VisMederi srl, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Carli","sequence":"additional","affiliation":[{"name":"VisMederi srl, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Lazzeri","sequence":"additional","affiliation":[{"name":"Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy"},{"name":"Interuniversity Research Center on Influenza and Other Transmissible Infections (CIRI-IT), 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Montomoli","sequence":"additional","affiliation":[{"name":"Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy"},{"name":"Interuniversity Research Center on Influenza and Other Transmissible Infections (CIRI-IT), 16132 Genoa, Italy"},{"name":"VisMederi srl, 53100 Siena, Italy"},{"name":"VisMederi Research srl, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7229-9919","authenticated-orcid":false,"given":"Claudia Maria","family":"Trombetta","sequence":"additional","affiliation":[{"name":"Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy"},{"name":"Interuniversity Research Center on Influenza and Other Transmissible Infections (CIRI-IT), 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3810\/pgm.2009.09.2051","article-title":"The first pandemic of the 21st century: A review of the 2009 pandemic variant influenza A (H1N1) virus","volume":"121","author":"Scalera","year":"2009","journal-title":"Postgrad. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Karageorgopoulos, D.E., Vouloumanou, E.K., Korbila, I.P., Kapaskelis, A., and Falagas, M. (2011). Age distribution of cases of 2009 (H1N1) pandemic influenza in comparison with seasonal influenza. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021690"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1056\/NEJMoa0906453","article-title":"Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus","volume":"361","author":"Hancock","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1086\/652441","article-title":"Recipients of vaccine against the 1976 \u201cswine flu\u201d have enhanced neutralization responses to the 2009 novel H1N1 influenza virus","volume":"50","author":"McCullers","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1093\/infdis\/jiw479","article-title":"Antibodies against the Current Influenza A(H1N1) Vaccine Strain Do Not Protect Some Individuals from Infection with Contemporary Circulating Influenza A(H1N1) Virus Strains","volume":"214","author":"Petrie","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1007\/s00705-017-3282-8","article-title":"Serological study of influenza viruses in veterinarians working with swine in Mexico","volume":"162","year":"2017","journal-title":"Arch. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.provac.2011.07.008","article-title":"Induction of cross-reactive antibodies to 2009 pandemic H1N1 influenza virus (H1N1) after seasonal vaccination (Winters 2003\/04 and 2007\/08)","volume":"4","author":"Iorio","year":"2011","journal-title":"Procedia Vaccinol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.4161\/hv.28313","article-title":"Influence of pre-existing hemagglutination inhibition titers against historical influenza strains on antibody response to inactivated trivalent influenza vaccine in adults 50\u201380 years of age","volume":"10","author":"Ross","year":"2014","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4543","DOI":"10.1016\/j.vaccine.2012.03.061","article-title":"Pre-vaccination immunity and immune responses to a cell culture-derived whole-virus H1N1 vaccine are similar to a seasonal influenza vaccine","volume":"30","author":"Ehrlich","year":"2012","journal-title":"Vaccine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1093\/infdis\/jiq039","article-title":"Immuno-epidemiologic correlates of pandemic H1N1 surveillance observations: Higher antibody and lower cell-mediated immune responses with advanced age","volume":"203","author":"Skowronski","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3558","DOI":"10.1016\/j.vaccine.2010.03.006","article-title":"Cross-reactive antibody responses to the 2009 A\/H1N1v influenza virus in the Italian population in the pre-pandemic period","volume":"28","author":"Rizzo","year":"2010","journal-title":"Vaccine"},{"key":"ref_12","unstructured":"World Health Organization (2020, July 20). WHO Recommendations on the Composition of Influenza Virus Vaccines. Available online: https:\/\/www.who.int\/influenza\/vaccines\/virus\/recommendations\/en\/."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"28403","DOI":"10.1074\/jbc.R110.129809","article-title":"Influenza hemagglutinin and neuraminidase membrane glycoproteins","volume":"285","author":"Gamblin","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Lopez, C.E., and Legge, K.L. (2020). Influenza a Virus Vaccination: Immunity, Protection, and Recent Advances Toward A Universal Vaccine. Vaccines, 8.","DOI":"10.3390\/vaccines8030434"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Manenti, A., Maciola, A.K., Trombetta, C.M., Kistner, O., Casa, E., Hyseni, I., Razzano, I., Torelli, A., and Montomoli, E. (2020). Influenza Anti-Stalk Antibodies: Development of a New Method for the Evaluation of the Immune Responses to Universal Vaccine. Vaccines, 8.","DOI":"10.3390\/vaccines8010043"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1586\/14760584.2016.1164046","article-title":"Influenza immunology evaluation and correlates of protection: A focus on vaccines","volume":"15","author":"Trombetta","year":"2016","journal-title":"Expert Rev. Vaccines"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1080\/14760584.2019.1639503","article-title":"Challenges in the development of egg-independent vaccines for influenza","volume":"18","author":"Trombetta","year":"2019","journal-title":"Expert Rev. Vaccines"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/BF01317390","article-title":"The application of a single radial haemolysis technique to foot-and-mouth disease virus-antibody study","volume":"64","author":"Rweyemamu","year":"1980","journal-title":"Arch. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jim.2015.04.009","article-title":"Validation of Single Radial Haemolysis assay: A reliable method to measure antibodies against influenza viruses","volume":"422","author":"Trombetta","year":"2015","journal-title":"J. Immunol. Methods"},{"key":"ref_20","unstructured":"European Medicines Agency (2016). Guideline on Influenza Vaccines. Non-Clinical and Clinical Module, European Medicines Agency."},{"key":"ref_21","unstructured":"National Center for Biotechnology Information (2020, July 20). Basic Local Alignment Search Tool, Available online: https:\/\/blast.ncbi.nlm.nih.gov."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Clark, A.M., DeDiego, M.L., Anderson, C.S., Wang, J., Yang, H., Nogales, A., Martinez-Sobrido, L., Zand, M.S., Sangster, M.Y., and Topham, D.J. (2017). Antigenicity of the 2015\u20132016 seasonal H1N1 human influenza virus HA and NA proteins. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0188267"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"15798","DOI":"10.1073\/pnas.1409171111","article-title":"Potential antigenic explanation for atypical H1N1 infections among middle-aged adults during the 2013\u20132014 influenza season","volume":"111","author":"Linderman","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/4\/656\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:29:37Z","timestamp":1760178577000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/4\/656"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,5]]},"references-count":23,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["vaccines8040656"],"URL":"https:\/\/doi.org\/10.3390\/vaccines8040656","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints202010.0100.v1","asserted-by":"object"}]},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,5]]}}}