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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02509

Mincle and STING-Stimulating Adjuvants Elicit Robust Cellular Immunity and Drive Long-Lasting Memory Responses in a Foot-and-Mouth Disease Vaccine

  • 1Animal and Plant Quarantine Agency (South Korea), South Korea
  • 2Other, South Korea

Conventional foot-and-mouth disease (FMD) vaccines have several limitations, such as slow induction of the antibody, short persistence of antibody titers, and low vaccine efficacy and safety in pigs. Despite the importance of the cellular immune response in the host defense at the early stages of foot-and-mouth disease virus (FMDV) infection, most FMD vaccines focus on humoral immune responses. Antibody responses alone are not sufficient to drive complete protection against FMDV infection, and cellular immunity is also required. From these perspectives, it is necessary to develop a new strategy for a novel FMD vaccine to induce a more potent cellular immune response and a long-lasting immune response as well as to address safety. Previously, we demonstrated the potential of various pattern recognition receptor (PRR) ligands and cytokines as adjuvants for the FMD vaccine. Based on these results, we investigated PRR ligands and a cytokine adjuvant-mediated memory response in mice and the cellular immune response in peripheral blood mononuclear cells (PBMCs) isolated from cattle and pigs. We further evaluated target-specific adjuvants, including Mincle, STING, TLR-7/8, and Dectin-1/2 ligand, for their role in generating ligand-mediated, long-lasting memory responses in cattle and pigs. The combination of the Mincle and STING-stimulating ligands, i.e., trehalose-6, 6’dibehenate (TDB) and bis-(3’-5’)-cyclic dimeric guanosine monophosphate (c-di-GMP), induced a high level of antigen-specific and virus-neutralizing antibody titers at the early stage of vaccination and maintained the long-lasting memory immune response in pigs. These findings will provide important clues for the development of a robust FMD vaccine that will stimulate both cellular and humoral immune responses to elicit a long-lasting, effective immune response and address the limitations of the current FMD vaccine.

Keywords: PRR ligands, Cytokines, adjuvants, Foot-and-Mouth Disease, Vaccine

Received: 27 Jun 2019; Accepted: 08 Oct 2019.

Copyright: © 2019 Lee, Jo, Shin, Kim, Kim, Shim and Park. 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) and the copyright owner(s) 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: Mx. Jong-Hyeon Park, Animal and Plant Quarantine Agency (South Korea), Gimcheon-si, North Gyeongsang, South Korea, parkjhvet@korea.kr