{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T13:26:34Z","timestamp":1776173194336,"version":"3.50.1"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T00:00:00Z","timestamp":1625443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014180","name":"Junta de Castilla y Le\u00f3n","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014180","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Sex differences in immune responses are well known. However, the humoral response in males and females in the case of influenza vaccination is yet to be characterized since studies have shown uneven results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective study was conducted in 2,243 individuals (46.9% males) divided by age (15\u201364 and \u226565 years old). A serological analysis was performed by hemagglutination inhibition assay (HI) just before and 28 days after annual vaccination against seasonal influenza viruses in people vaccinated during the 2006\u20132018 seasons. A comparison of the humoral responses against influenza A and B viruses contained in the vaccine, between male and female individuals in young adults and elderly was conducted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Significative higher humoral response against classical influenza A (H1N1), A(H1N1)pdm09 subtype and B\/Victoria lineage in terms of seroconversion rate were found in elderly women. No significant differences were found in the case of A(H3N2) subtype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Elderly women seem to display a greater humoral response against classical A(H1N1), pandemic A(H1N1)pmd09 and B\/Victoria lineage than elderly men. Sex dimorphism does not affect young adults.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.715688","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T06:44:04Z","timestamp":1625467444000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Do Vaccines Need a Gender Perspective? Influenza Says Yes!"],"prefix":"10.3389","volume":"12","author":[{"given":"Laura","family":"S\u00e1nchez-de Prada","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ra\u00fal","family":"Ortiz de Lejarazu-Leonardo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Castrodeza-Sanz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Tamayo-G\u00f3mez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Mar\u00eda","family":"Eiros-Bouza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iv\u00e1n","family":"Sanz-Mu\u00f1oz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"6317","DOI":"10.1038\/s41467-020-19741-6","article-title":"Male Sex Identified by Global COVID-19 Meta-Analysis as a Risk Factor for Death and ITU Admission","volume":"11","author":"Peckham","year":"2020","journal-title":"Nat Commun"},{"key":"B2","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1189\/jlb.0811427","article-title":"Mechanisms of Sex Disparities in Influenza Pathogenesis","volume":"92","author":"Klein","year":"2012","journal-title":"J Leukocyte Biol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.3.476-488.2001","article-title":"Sex-Associated Hormones and Immunity to Protozoan Parasites","volume":"14","author":"Roberts","year":"2001","journal-title":"Clin Microbiol Rev"},{"key":"B4","article-title":"Sex, Gender and Influenza","volume-title":"WHO Libr Cat Data","year":"2010"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.091823","article-title":"Risk of Severe Outcomes Among Patients Admitted to Hospital With Pandemic (H1N1) Influenza","volume":"182","author":"Campbell","year":"2010","journal-title":"Can Med Assoc J C"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.1496","article-title":"Critically Ill Patients With 2009 Influenza A(H1N1) Infection in Canada","volume":"302","author":"Kumar","year":"2009","journal-title":"JAMA - J Am Med Assoc"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.5694\/j.1326-5377.2010.tb03424.x","article-title":"Hospitalised Adult Patients With Pandemic (H1N1) 2009 Influenza in Melbourne, Australia","volume":"192","author":"Denholm","year":"2010","journal-title":"Med J Aust"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e19409","DOI":"10.1371\/journal.pone.0019409","article-title":"Sex- and Age-Related Differences in Morbidity Rates of 2009 Pandemic Influenza a H1N1 Virus of Swine Origin in Japan","volume":"6","author":"Eshima","year":"2011","journal-title":"PloS One"},{"key":"B9","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/BF01586187","article-title":"Gender Differences in Local and Systemic Reactions to Inactivated Influenza Vaccine, Established by a Meta-Analysis of Fourteen Independent Studies","volume":"15","author":"Beyer","year":"1996","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1001\/archinternmed.2008.513","article-title":"Half- vs Full-Dose Trivalent Inactivated Influenza Vaccine (2004-2005): Age, Dose, and Sex Effects on Immune Responses","volume":"168","author":"Engler","year":"2008","journal-title":"Arch Intern Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2008.04.054","article-title":"Sexual Dimorphism of Humoral Immunity With Human Vaccines","volume":"26","author":"Cook","year":"2008","journal-title":"Vaccine"},{"key":"B12","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1007\/s13205-021-02642-w","article-title":"A Changing Trend in Diagnostic Methods of Influenza A (H3N2) Virus in Human: A Review","volume":"11","author":"Mohan","year":"2021","journal-title":"3 Biotech"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1099\/jgv.0.001348","article-title":"Passage of Influenza A\/H3N2 Viruses in Human Airway Cells Removes Artefactual Variants Associated With Neuraminidase-Mediated Binding","volume":"101","author":"Brown","year":"2020","journal-title":"J Gen Virol"},{"key":"B14","unstructured":"WHO Recommendations on the Composition of Influenza Virus Vaccines"},{"key":"B15","volume-title":"Manual for the Laboratory Diagnosis and Virological Surveillance of Influenza., Ed. WHOCCs","year":"2011"},{"key":"B16","doi-asserted-by":"publisher","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":"B17","doi-asserted-by":"publisher","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":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2019.10.091","article-title":"Is There a Difference in the Immune Response, Efficacy, Effectiveness and Safety of Seasonal Influenza Vaccine in Males and Females?-A Systematic Review","volume":"38","author":"Tadount","year":"2020","journal-title":"Vaccine"},{"key":"B19","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/1471-2334-10-71","article-title":"Safety, Efficacy, and Immunogenicity of an Inactivated Influenza Vaccine in Healthy Adults: A Randomized, Placebo-Controlled Trial Over Two Influenza Seasons","volume":"10","author":"Jackson","year":"2010","journal-title":"BMC Infect Dis"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1321060111","article-title":"Systems Analysis of Sex Differences Reveals an Immunosuppressive Role for Testosterone in the Response to Influenza Vaccination","volume":"111","author":"Furman","year":"2014","journal-title":"Proc Natl Acad Sci USA"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/nri2394","article-title":"The X-Files in Immunity: Sex-Based Differences Predispose Immune Responses","volume":"8","author":"Fish","year":"2008","journal-title":"Nat Rev Immunol"},{"key":"B22","doi-asserted-by":"crossref","DOI":"10.1038\/2141224a0","article-title":"Influence of Sex on Immunoglobulin Levels","author":"Butterworth","year":"1967"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(10)70049-9","article-title":"The Xs and Y of Immune Responses to Viral Vaccines","volume":"10","author":"Klein","year":"2010","journal-title":"Lancet Infect Dis"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201200099","article-title":"Sex Influences Immune Responses to Viruses, and Efficacy of Prophylaxis and Therapeutic Treatments for Viral Diseases","volume":"34","author":"Klein","year":"2012","journal-title":"Bioessays"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/s100960000305","article-title":"Effect on Diphtheria Immunity of Combined Tetanus and Diphtheria Booster Vaccination in Adults","volume":"19","author":"Marlovits","year":"2000","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2005.01.085","article-title":"Insufficient Protection for Healthy Elderly Adults by Tetanus and TBE Vaccines","volume":"23","author":"Hainz","year":"2005","journal-title":"Vaccine"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(98)00269-2","article-title":"Seroprevalence and Determinants of Diphtheria, Tetanus and Poliomyelitis Antibodies Among Adults in Berlin, Germany","volume":"17","author":"Stark","year":"1999","journal-title":"Vaccine"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2007.08.042","article-title":"Safety and Immunogenicity of a High Dosage Trivalent Influenza Vaccine Among Elderly Subjects","volume":"25","author":"Couch","year":"2007","journal-title":"Vaccine"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1086\/599790","article-title":"Randomized, Double-Blind Controlled Phase 3 Trial Comparing the Immunogenicity of High-Dose and Standard-Dose Influenza Vaccine in Adults 65 Years of Age and Older","volume":"200","author":"Falsey","year":"2009","journal-title":"J Infect Dis"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/gene.2016.34","article-title":"Gene Signatures Associated With Adaptive Humoral Immunity Following Seasonal Influenza A\/H1N1 Vaccination","volume":"17","author":"Ovsyannikova","year":"2016","journal-title":"Genes Immun"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00180","article-title":"Sex Differences in Older Adults\u2019 Immune Responses to Seasonal Influenza Vaccination","volume":"10","author":"Voigt","year":"2019","journal-title":"Front Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01269","article-title":"The Confluence of Sex Hormones and Aging on Immunity","volume":"9","author":"Gubbels Bupp","year":"2018","journal-title":"Front Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.09.110","article-title":"Antibody Responses and Cross Protection Against Lethal Influenza A Viruses Differ Between the Sexes in C57BL\/6 Mice","volume":"29","author":"Lorenzo","year":"2011","journal-title":"Vaccine"},{"key":"B34","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1046\/j.1365-2249.2002.01780.x","article-title":"The Strength of B Cell Immunity in Female Rhesus Macaques Is Controlled by CD8+ T Cells Under the Influence of Ovarian Steroid Hormones","volume":"128","author":"L\u00fc","year":"2002","journal-title":"Clin Exp Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.01.080","article-title":"7-Estradiol Restores Antibody Responses to an Influenza Vaccine in a Postmenopausal Mouse Model","volume":"29","author":"Nguyen","year":"2011","journal-title":"Vaccine"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.715688\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T06:44:10Z","timestamp":1625467450000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.715688\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,5]]},"references-count":35,"alternative-id":["10.3389\/fimmu.2021.715688"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.715688","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,5]]},"article-number":"715688"}}