Frontiers in Immunology (Mar 2022)

Enhanced Immune Responses in Mice Induced by the c-di-GMP Adjuvanted Inactivated Vaccine for Pseudorabies Virus

  • Liting Hou,
  • Liting Hou,
  • Liting Hou,
  • Liting Hou,
  • Xiaoming Yu,
  • Xiaoming Yu,
  • Xiaoming Yu,
  • Xiaoming Yu,
  • Yuanyuan Zhang,
  • Yuanyuan Zhang,
  • Yuanyuan Zhang,
  • Yuanyuan Zhang,
  • Luping Du,
  • Luping Du,
  • Luping Du,
  • Luping Du,
  • Yuanpeng Zhang,
  • Yuanpeng Zhang,
  • Yuanpeng Zhang,
  • Yuanpeng Zhang,
  • Haiwei Cheng,
  • Haiwei Cheng,
  • Haiwei Cheng,
  • Haiwei Cheng,
  • Qisheng Zheng,
  • Qisheng Zheng,
  • Qisheng Zheng,
  • Qisheng Zheng,
  • Jin Chen,
  • Jin Chen,
  • Jin Chen,
  • Jin Chen,
  • Jibo Hou,
  • Jibo Hou,
  • Jibo Hou,
  • Jibo Hou

DOI
https://doi.org/10.3389/fimmu.2022.845680
Journal volume & issue
Vol. 13

Abstract

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Cyclic dimeric guanosine monophosphate (c-di-GMP) is a bacterial second messenger with immunomodulatory activities in mice, suggesting potential applications as a vaccine immunopotentiator or therapeutic agent. In this study, we evaluated the efficacy of c-di-GMP as an immunopotentiator for pseudorabies virus (PRV) inactivated vaccine in a murine model. We found that c-di-GMP improved the humoral and cellular immune responses induced by PRV inactivated vaccine and its effects on immunity reached the level comparable to that of a live attenuated vaccine. Furthermore, c-di-GMP enhanced the murine antibody response against the viral glycoprotein gB up to 120 days after immunization. The c-di-GMP–adjuvanted PRV inactivated vaccine induced long-term humoral immunity by promoting a potent T follicular helper cell response, which is known to directly control the magnitude of the germinal center B cell response. Furthermore, the c-di-GMP enhanced the response of bone marrow plasma cells and upregulated the expression of Bcl-2 and Mcl-1, which have been identified as anti-apoptotic regulatory genes of germinal center and memory B cells. Our findings open a new avenue for improving the immune efficacy of PRV inactivated vaccines.

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