{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T10:46:14Z","timestamp":1777200374963,"version":"3.51.4"},"posted":{"date-parts":[[2026,4,22]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":27,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Background<\/jats:p>\n                <jats:p>Although the hemagglutination inhibition (HAI) titer remains the gold standard correlate of protection against influenza, it does not fully capture the broader antibody responses that contribute to immunity.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We analyzed immune responses in paired pre-infection and convalescent sera from 306 RT-PCR\u2013confirmed A\/H3N2 infections from two household studies (2014\u201318) in Managua, Nicaragua. Antibody responses were measured by HAI and enzyme-linked immunosorbent assays (ELISAs) against full-length hemagglutinin (HA), the HA stalk, and neuraminidase (NA). Participants were classified as HAI responders (\u22654-fold HAI rise), alternate responders (no HAI rise but \u22654-fold boost in \u22651 ELISA), or no-response individuals (no \u22654-fold rise in any assay). We compared demographic, clinical, and pre-infection antibody characteristics across these groups. We also analyzed predictors of an NA response.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Overall, 77% of participants had HAI seroconversion or a 4-fold rise. Among the 23% HAI non-responders, 62% had alternate antibody responses. No-response individuals had the highest pre-infection HAI and full-length HA titers (p &lt; 0.0001), the lowest viral loads, and the fewest fever or influenza like illness (ILI) symptoms (p &lt; 0.01). An NA response was more common among symptomatic individuals (p = 0.0483) and those with low or high baseline NA titers.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>High baseline HAI titers can limit detectable 4-fold rises and are associated with milder illness. Evaluating additional immune responses may capture a more complete picture of the host response to infection, thereby improving surveillance and informing vaccine development.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.04.21.26351404","type":"posted-content","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:13Z","timestamp":1776902413000},"source":"Crossref","is-referenced-by-count":0,"title":["Hemagglutination inhibition and alternate serologic responses following Influenza A(H3N2) virus infection"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9368-4780","authenticated-orcid":false,"given":"Boshu","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Epidemiology, School of Public Health, University of Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0107-6173","authenticated-orcid":false,"given":"Jose Victor","family":"Zambrana","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health, University of Michigan, USA"},{"name":"Sustainable Sciences Institute, Managua, Nicaragua"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4348-428X","authenticated-orcid":false,"given":"Abigail","family":"Shotwell","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health, University of Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0070-3895","authenticated-orcid":false,"given":"Nery","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Sustainable Sciences Institute, Managua, Nicaragua"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4153-2615","authenticated-orcid":false,"given":"Miguel","family":"Plazaola","sequence":"additional","affiliation":[{"name":"Sustainable Sciences Institute, Managua, Nicaragua"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio","family":"Ojeda","sequence":"additional","affiliation":[{"name":"Sustainable Sciences Institute, Managua, Nicaragua"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger","family":"Lopez","sequence":"additional","affiliation":[{"name":"Sustainable Sciences Institute, Managua, Nicaragua"},{"name":"Centro de Salud S\u00f3crates Flores Vivas, Ministry of Health, Managua, Nicaragua"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6792-7650","authenticated-orcid":false,"given":"Daniel","family":"Stadlbauer","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine a Mount Sinai, New York, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5251-173X","authenticated-orcid":false,"given":"Guillermina","family":"Kuan","sequence":"additional","affiliation":[{"name":"Sustainable Sciences Institute, Managua, Nicaragua"},{"name":"Centro de Salud S\u00f3crates Flores Vivas, Ministry of Health, Managua, Nicaragua"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3812-5978","authenticated-orcid":false,"given":"Angel","family":"Balmaseda","sequence":"additional","affiliation":[{"name":"Sustainable Sciences Institute, Managua, Nicaragua"},{"name":"Centro Nacional de Diagn\u00f3stico y Referencia, Ministry of Health, Managua, Nicaragua"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4121-776X","authenticated-orcid":false,"given":"Florian","family":"Krammer","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine a Mount Sinai, New York, NY, USA"},{"name":"Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Ignaz Semmelweis Institute, Interuniversity Institute for Infection Research, Medical University of Vienna, Vienna, Austria"},{"name":"Ludwig Boltzmann Institute for Science Outreach and Pandemic Preparedness at the Medical University of Vienna, Vienna, 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