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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1439418
This article is part of the Research Topic Vaccines and Therapeutics Utilizing New Adjuvants and Potential Inhibitors to Target Emerging Infectious Diseases View all articles

The adjuvant BcfA activates antigen presenting cells through TLR4 and supports TFH and TH1 while attenuating TH2 gene programming

Provisionally accepted
Mohamed M. Shamseldin Mohamed M. Shamseldin 1Kaitlin A. Read Kaitlin A. Read 2Jesse M. Hall Jesse M. Hall 1Jasmine A. Tuazon Jasmine A. Tuazon 1Jessica M. Brown Jessica M. Brown 1Myra Guo Myra Guo 1Yash A. Gupta Yash A. Gupta 1Rajendar K. Deora Rajendar K. Deora 1Ken Oestreich Ken Oestreich 1Purnima Dubey Purnima Dubey 1*
  • 1 The Ohio State University, Columbus, United States
  • 2 University of Pennsylvania, Philadelphia, Pennsylvania, United States

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

    Adjuvants added to subunit vaccines augment antigen-specific immune responses. One mechanism of adjuvant action is activation of pattern recognition receptors (PRRs) on innate immune cells. Bordetella colonization factor A (BcfA); an outer membrane protein with adjuvant function, activates TH1/TH17-polarized immune responses to protein antigens from Bordetella pertussis and SARS CoV-2. Unlike other adjuvants, BcfA does not elicit a TH2 response. To understand the mechanism of BcfA-driven TH1/TH17 vs. TH2 activation, we screened PRRs to identify pathways activated by BcfA and showed that BcfA activates antigen presenting cells through murine TLR4. We tested the role of this receptor in the BcfA-mediated activation of bone marrow-derived dendritic cells (BMDCs) using mice with germline deletion of TLR4. We found that BcfA-treated WT BMDCs upregulated expression of the costimulatory molecules CD40, CD80, and CD86 and produced IL-6, IL-12/23 p40, and TNF-α while TLR4 KO BMDCs were not activated. Furthermore, human PBMCs stimulated with BcfA produced IL-6. BcfA-stimulated murine BMDCs also exhibited increased uptake of the antigen DQ-OVA, supporting a role for BcfA in improving antigen presentation to T cells. BcfA further activated APCs in murine lungs.Using an in vitro TH cell polarization system, we found that BcfA-stimulated BMDC supernatant supported TFH and TH1 while suppressing TH2 gene programming. Overall, these data provide mechanistic understanding of how this novel adjuvant activates immune responses.

    Keywords: adjuvants, antigen presenting cells, BCFA, T cell polarization, Pattern Recognition Receptors

    Received: 27 May 2024; Accepted: 09 Aug 2024.

    Copyright: © 2024 Shamseldin, Read, Hall, Tuazon, Brown, Guo, Gupta, Deora, Oestreich and Dubey. 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: Purnima Dubey, The Ohio State University, Columbus, 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.