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

Vaccines
Phoebe E LewisQizhi Yao

Abstract

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 ...Continue Reading

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Citations

Jul 16, 2020·Pharmaceutics·Alba Martín-MorenoMaría Angeles Muñoz-Fernández

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Methods Mentioned

BETA
FACS
flow cytometry
transgenic
Assay
ELISA
ELISAs

Software Mentioned

Graphpad
Flow Jo
Graphpad Prism

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