{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T17:05:32Z","timestamp":1775840732983,"version":"3.50.1"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Obesity is increasing globally, and it negatively impacts influenza vaccine efficacy. Although sex differences in influenza vaccine responses are studied in non-obese hosts, studies investigating sex differences in influenza vaccine-induced immunity and protection during obesity are limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      Using the C57BL\/6J mouse model of high-fat diet (HFD)-induced obesity or low-fat diet controls, we investigated sex differences in influenza vaccine-induced immunity and protection during obesity. Male and female mice with or without obesity were vaccinated intramuscularly twice at a 3-week interval with an inactivated 2009 H1N1 influenza A virus (IAV) vaccine. At 35 days post-vaccination (dpv), antibody responses in plasma and B- and T-cell responses in spleen and bone marrow were quantified. At 42 dpv, mice were intranasally challenged with a drift variant of the H1N1 IAV, and disease severity was assessed by monitoring the change in body mass up to 21 days post-challenge (dpc). Subsets of mice were euthanized at 3 dpc to determine pulmonary virus replication (TCID\n                      <jats:sub>50<\/jats:sub>\n                      assay), histopathology (H&amp;amp;E staining), and cytokine\/chemokine responses (multiplex ELISA).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Female mice, irrespective of diet and obesity status, developed higher antibody responses and were better protected compared to males. Vaccinated males with obesity mounted the poorest antibody responses, experienced a more severe disease, were unable to clear replicating virus from the lungs effectively, and demonstrated heightened pulmonary inflammation. Despite these differences, splenic B- and T-cell frequencies were comparable, suggesting the inefficiency of B cells to produce antibodies in males but not in females with obesity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our findings suggest that sex differences are observed in influenza vaccine-induced immunity and protection during obesity, where males are more severely affected. These findings highlight the importance of considering biological sex and obesity status in influenza vaccine design and testing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1699275","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T13:33:46Z","timestamp":1766064826000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Females with obesity exhibit greater influenza vaccine-induced immunity and protection than males in a mouse 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Magar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tawfik","family":"Aboellail","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santosh","family":"Dhakal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.595109","article-title":"Obesity increases the severity and mortality of influenza and COVID-19: A systematic review and meta-analysis","volume":"11","author":"Zhao","year":"2020","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-022-04689-0","article-title":"Obesity as a risk factor for severe influenza infection in children and adolescents: a systematic review and 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