1 IFN-α Modulates Memory Tfh Cells and Memory B Cells in Mice, Following Recombinant FMDV Adenoviral Challenge

• Published in: Frontiers in immunology 2020, Vol.11, p.701
• Main Authors: Duan, Xiangguo, Sun, Peng, Lan, Yaru, Shen, Chunxiu, Zhang, Xiaoyu, Hou, Shaozhang, Chen, Jian, Ma, Bin, Xia, Yuhan, Su, Chunxia
• Format: Article
• Language: English
• Subjects: Adenoviridae - genetics; Adenovirus Vaccines - administration & dosage; Adenovirus Vaccines - immunology; Adjuvants, Immunologic - pharmacology; Animals; B-Lymphocytes - immunology; Capsid Proteins - immunology; Female; Foot-and-Mouth Disease - immunology; Foot-and-Mouth Disease - prevention & control; Foot-and-Mouth Disease - virology; Foot-and-Mouth Disease Virus - immunology; Genetic Vectors - administration & dosage; Genetic Vectors - metabolism; Immunologic Memory - drug effects; Interferon-alpha - pharmacology; Mice; Mice, Inbred BALB C; T Follicular Helper Cells - immunology; Vaccination - methods; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - immunology
• ISSN: 1664-3224

Follicular helper T (Tfh) cells regulate high-affinity antibody production. Some findings have indicated that Tfh cells could be differentiated into memory cells. Here we have investigated the effects of IFN-α, as an adjuvant, on the generation of memory Tfh cell and memory B cell responses. The data showed that adenoviral vectors expressing: (i) foot-and-mouth disease virus (FMDV) VP1 proteins and porcine IFN-α, or (ii) porcine IFN-α alone, potently enhanced the generation of memory Tfh cells, especially the CCR7 memory Tfh subset. Upon rechallenge with FMD recombinant adenoviral vaccines, IFN-α enhances Tfh cells activity, rapidly upregulating their signature Bcl-6, CXCR5, and IL-21 markers. The results suggest that IFN-α enhances the levels of the transcription factor Bcl-6 within Tfh cells, potentially by regulating STAT1. Additionally, IFN-α substantially increased the number of IgG1 and CD86 memory B cells, which are responsible for inducing the rapid effector functions of memory Tfh cells after vaccine reactivation, establishing the close relationship between memory B cell and memory Tfh cell subsets. In brief, IFN-α enhances the potency of FMD recombinant adenoviral vaccines to induce memory Tfh and memory B cell responses, thus elevating serum antibody titers. IFN-α administration therefore represents an attractive strategy for enhancing responses to vaccination.