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Open AccessArticle

CTLA-4 Blockade, during HIV Virus-Like Particles Immunization, Alters HIV-Specific B-Cell Responses

1
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
2
Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX 77030, USA
3
Duke Human Vaccine Institute, Departments of Medicine, Immunology, Surgery, and Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27708, USA
4
Center for Translational Research on Inflammatory Diseases (CTRID), Michael E. DeBakey VA Medical Center, Houston, TX 77030, USA
*
Author to whom correspondence should be addressed.
Vaccines 2020, 8(2), 284; https://doi.org/10.3390/vaccines8020284
Received: 8 May 2020 / Revised: 31 May 2020 / Accepted: 3 June 2020 / Published: 6 June 2020
(This article belongs to the Section HIV Vaccines)
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. View Full-Text
Keywords: CTLA-4; HIV; vaccine; VLP; B-cell; Tfh; immunotherapy; antibody CTLA-4; HIV; vaccine; VLP; B-cell; Tfh; immunotherapy; antibody
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Lewis, P.E.; Poteet, E.C.; Liu, D.; Chen, C.; LaBranche, C.C.; Stanfield-Oakley, S.A.; Montefiori, D.C.; Ferrari, G.; Yao, Q. CTLA-4 Blockade, during HIV Virus-Like Particles Immunization, Alters HIV-Specific B-Cell Responses. Vaccines 2020, 8, 284.

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