Sex differences in antibody responses to influenza A/H3N2 across the life course

Sex differences in antibody responses to influenza A/H3N2 across the life course | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Sex differences in antibody responses to influenza A/H3N2 across the life course C Jessica Metcalf, Siyu Chen, Bernardo García-Carreras, James Hay, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7960157/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Sex differences in both innate and adaptive immunity are increasingly recognized as shaping responses to a range of pathogens. For antigenically variable pathogens that infect people many times over their lifetime, like influenza, sex differences may accumulate or be obscured by the interplay of immunity derived from each infection and future risk. However, sex-specific lifetime trajectories of influenza immunity are poorly characterized. Here, we analyzed hemagglutination inhibition antibody titers to multiple strains of influenza A/H3N2, measured in individuals spanning a wide age range to disentangle strain-specific and cross-reactive antibody responses by sex. To account for potential differences in exposure, we separately analyzed antibody titers to: (1) viruses circulating during an individual’s lifetime, and (2) viruses isolated before birth (pre-birth) or after sampling, with responses to the latter interpreted as exclusively cross-reactive, given the absence of possible exposure to these strains. We found that females aged 15 to 40 generally have higher antibody titers than males against pre-birth and post-sampling strains, consistent with greater cross-reactivity. Conversely, older males have stronger responses to strains that they could have encountered during their lives, suggesting that they mount stronger responses upon infection. Biological sciences/Immunology/Infectious diseases/Influenza virus Health sciences/Diseases/Infectious diseases/Influenza virus influenza A/H3N2 hemagglutination inhibition antibody sex age cross reactivity Full Text Additional Declarations Yes there is potential Competing Interest. B.G.-C. and D.A.T.C. received financial research support through their institution from Merck for unrelated work; D.A.T.C. receives financial research support through a grant to his institution from Pfizer for unrelated work; J.L. receives research support from CDC and NIH-NIGMS for unrelated work; S.R. receives grants from the Wellcome Trust; CJEM was funded by Princeton Precision Health. The other authors declare no competing interests. Supplementary Files SIflusex.pdf Sex differences in antibody responses to influenza A/H3N2 across the life course Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7960157","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":545274984,"identity":"d51d8331-0d61-46d3-b97c-91d747379926","order_by":0,"name":"C Jessica Metcalf","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/ElEQVRIiWNgGAWjYFCCA2BShr29gYEhAS7KRkALEPHwnDkA0cJDWAsDVMsNqBUEtfA3nk58/KHGjodH8u2xDw932MnZs/ceYPhQdhinFokDZzcbHDiWzMMjnZc8I/FMsjEPz7kExhnncGsxYDi7TeJgAzOPvXSOMUNi24HEHokcA2beNrxatv842FAPdNgZsJZ6sJa/+LVsYzjYcJiHR4IHrCWBB6SFEY8WkF8kzhw7zsPDk5cM1JJs2HPmjMHBnnPpOLXwzzi78UNFTbUcD/vZw4w/2+zk2dt7DB/8KLPGqQVoDYzFgxA8gKkO2ZoGLFpGwSgYBaNgFCADAH+rVpXNsi6aAAAAAElFTkSuQmCC","orcid":"","institution":"Princeton University","correspondingAuthor":true,"prefix":"","firstName":"C","middleName":"Jessica","lastName":"Metcalf","suffix":""},{"id":545274985,"identity":"60a95639-2287-44d2-9643-d2d4db1fa316","order_by":1,"name":"Siyu Chen","email":"","orcid":"","institution":"High Meadows Environmental Institute, Princeton University; 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