| Autor: |
Phoebe E. Lewis, Ethan C. Poteet, Dongliang Liu, Changyi Chen, Celia C. LaBranche, Sherry A. Stanfield-Oakley, David C. Montefiori, Guido Ferrari, Qizhi Yao |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
Vaccines, Vol 8, Iss 2, p 284 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2076-393X |
| DOI: |
10.3390/vaccines8020284 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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