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To identify determinants of vaccine efficacy, we used data from &gt;\u20091,300 vaccination events to predict the response to vaccination measured as seroconversion as well as hemagglutination inhibition (HAI) titer levels one year after. We evaluated the predictive capabilities of age, body mass index (BMI), sex, race, comorbidities, vaccination history, and baseline HAI titers, as well as vaccination month and vaccine dose in multiple linear regression models. The models predicted the categorical response for &gt;\u200975% of the cases in all subsets with one exception. Prior vaccination, baseline titer level, and age were the major determinants of seroconversion, all of which had negative effects. Further, we identified a gender effect in older participants and an effect of vaccination month. BMI had a surprisingly small effect, likely due to its correlation with age. Comorbidities, vaccine dose, and race had negligible effects. Our models can generate a new seroconversion score that is corrected for the impact of these factors which can facilitate future biomarker identification.<\/jats:p>","DOI":"10.15252\/msb.202110724","type":"journal-article","created":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T03:30:12Z","timestamp":1651807812000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Evaluation of determinants of the serological response to the quadrivalent split\u2010inactivated influenza vaccine"],"prefix":"10.1038","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4751-7854","authenticated-orcid":false,"given":"Shaohuan","family":"Wu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ted M","family":"Ross","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A","family":"Carlock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elodie","family":"Ghedin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6687-3088","authenticated-orcid":false,"given":"Hyungwon","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2856-3118","authenticated-orcid":false,"given":"Christine","family":"Vogel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,5,6]]},"reference":[{"key":"BFMSB202110724_CR1","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.132155","volume":"5","author":"RB Abreu","year":"2020","unstructured":"Abreu RB, Kirchenbaum GA, Clutter EF, Sautto GA, Ross TM (2020) Preexisting subtype immunodominance shapes memory B cell recall response to influenza vaccination. 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