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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Mucosal Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1386243
This article is part of the Research Topic Advances in Understanding Mucosal Immunity in Coronaviruses: From Mechanisms to Vaccines View all articles

Sex-biased immunogenicity of a mucosal subunit vaccine against SARS-CoV-2 in mice

Provisionally accepted
Jianping Li Jianping Li 1*Kevin S. Hsu Kevin S. Hsu 2Savannah E. Howe Savannah E. Howe 3Tanya Hoang Tanya Hoang 2Zheng Xia Zheng Xia 2Jay A. Berzofsky Jay A. Berzofsky 2*Yongjun Sui Yongjun Sui 2*
  • 1 Center for Cancer Rsearch, National Cancer Institute Bethesda, Bethesda, Illinois, United States
  • 2 Center for Cancer Research, National Cancer Institute Bethesda, Bethesda, Illinois, United States
  • 3 Vaccine Branch, Center for Cancer Research, National Cancer Institute/National Institutes of Health, Bethesda, United States

The final, formatted version of the article will be published soon.

    Current vaccines against COVID-19 administered via parenteral route have limited ability to induce mucosal immunity. There is a need for an effective mucosal vaccine to combat SARS-CoV-2 virus replication in the respiratory mucosa. Moreover, sex differences are known to affect systemic antibody responses against vaccines. However, their role in mucosal cellular responses against a vaccine remains unclear and is underappreciated. We evaluated the mucosal immunogenicity of a booster vaccine regimen that is recombinant protein-based and administered intranasally in mice to explore sex differences in mucosal humoral and cellular responses. Our results showed that vaccinated mice elicited strong systemic antibody (Ab), nasal, and bronchiole alveolar lavage (BAL) IgA responses, and local T cell immune responses in the lung in a sex-biased manner irrespective of mouse genetic background. Monocytes, alveolar macrophages, and CD103+ resident dendritic cells (DCs) in the lungs are correlated with robust mucosal Ab and T cell responses induced by the mucosal vaccine. Our findings provide novel insights into optimizing next-generation booster vaccines against SARS-CoV-2 by inducing spike-specific lung T cell responses, as well as optimizing mucosal immunity for other respiratory infections, and a rationale for considering sex differences in future vaccine research and vaccination practice.

    Keywords: SARS-CoV-2, Mucosal vaccine, Lung tissue-resident T cells, innate immunity, and Sex differences

    Received: 14 Feb 2024; Accepted: 06 May 2024.

    Copyright: © 2024 Li, Hsu, Howe, Hoang, Xia, Berzofsky and Sui. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Jianping Li, Center for Cancer Rsearch, National Cancer Institute Bethesda, Bethesda, 20892, Illinois, United States
    Jay A. Berzofsky, Center for Cancer Research, National Cancer Institute Bethesda, Bethesda, 20892, Illinois, United States
    Yongjun Sui, Center for Cancer Research, National Cancer Institute Bethesda, Bethesda, 20892, Illinois, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.