期刊
VACCINES
卷 8, 期 2, 页码 -出版社
MDPI
DOI: 10.3390/vaccines8020284
关键词
CTLA-4; HIV; vaccine; VLP; B-cell; Tfh; immunotherapy; antibody
资金
- VA Merit Award [1I01BX001474-01A1]
- NIH Initiative for Maximizing Student Development (IMSD) [R25GM56929]
- Cytometry and Cell Sorting Core at Baylor College of Medicine
- NIH [P30 AI036211, P30 CA125123, S10 RR024574]
- Baylor-UT Houston Center for AIDS Research (CFAR), an NIH [AI036211]
Studies have shown that blockade of CTLA-4 promoted the expansion of germinal center B-cells in viral infection or immunization with model antigens. Few studies have evaluated the immunological consequences of CTLA-4 blockade during immunization against relevant vaccine candidates. Here, we investigated the effects of CTLA-4 blockade on HIV virus-like particles (VLPs) vaccination in a C57BL/6J mouse model. We found that CTLA-4 blockade during HIV VLP immunization resulted in increased CD4+ T-cell activation, promoted the expansion of HIV envelope (Env)-specific follicular helper T cell (Tfh) cells, and significantly increased HIV Gag- and Env-specific IgG with higher avidity and antibody-dependent cellular cytotoxicity (ADCC) capabilities. Furthermore, after only a single immunization, CTLA-4 blockade accelerated T-cell dependent IgG class switching and the induction of significantly high serum levels of the B-cell survival factor, A proliferation-inducing ligand (APRIL). Although no significant increase in neutralizing antibodies was observed, increased levels of class-switched Env- and Gag-specific IgG are indicative of increased polyclonal B-cell activation, which demonstrated the ability to mediate and enhance ADCC in this study. Altogether, our findings show that CTLA-4 blockade can increase the levels of HIV antigen-specific B-cell and antigen-specific Tfh cell activity and impact humoral immune responses when combined with a clinically relevant HIV VLP-based vaccine.
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