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

Publication ,  Journal Article
Lewis, PE; Poteet, EC; Liu, D; Chen, C; LaBranche, CC; Stanfield-Oakley, SA; Montefiori, DC; Ferrari, G; Yao, Q
Published in: Vaccines (Basel)
June 6, 2020

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.

Duke Scholars

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Published In

Vaccines (Basel)

DOI

ISSN

2076-393X

Publication Date

June 6, 2020

Volume

8

Issue

2

Location

Switzerland

Related Subject Headings

  • 3207 Medical microbiology
  • 3204 Immunology
  • 3202 Clinical sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lewis, P. E., Poteet, E. C., Liu, D., Chen, C., LaBranche, C. C., Stanfield-Oakley, S. A., … Yao, Q. (2020). CTLA-4 Blockade, during HIV Virus-Like Particles Immunization, Alters HIV-Specific B-Cell Responses. Vaccines (Basel), 8(2). https://doi.org/10.3390/vaccines8020284
Lewis, Phoebe E., Ethan C. Poteet, Dongliang Liu, Changyi Chen, Celia C. LaBranche, Sherry A. Stanfield-Oakley, David C. Montefiori, Guido Ferrari, and Qizhi Yao. “CTLA-4 Blockade, during HIV Virus-Like Particles Immunization, Alters HIV-Specific B-Cell Responses.Vaccines (Basel) 8, no. 2 (June 6, 2020). https://doi.org/10.3390/vaccines8020284.
Lewis PE, Poteet EC, Liu D, Chen C, LaBranche CC, Stanfield-Oakley SA, et al. CTLA-4 Blockade, during HIV Virus-Like Particles Immunization, Alters HIV-Specific B-Cell Responses. Vaccines (Basel). 2020 Jun 6;8(2).
Lewis, Phoebe E., et al. “CTLA-4 Blockade, during HIV Virus-Like Particles Immunization, Alters HIV-Specific B-Cell Responses.Vaccines (Basel), vol. 8, no. 2, June 2020. Pubmed, doi:10.3390/vaccines8020284.
Lewis PE, Poteet EC, Liu D, Chen C, LaBranche CC, Stanfield-Oakley SA, Montefiori DC, Ferrari G, Yao Q. CTLA-4 Blockade, during HIV Virus-Like Particles Immunization, Alters HIV-Specific B-Cell Responses. Vaccines (Basel). 2020 Jun 6;8(2).

Published In

Vaccines (Basel)

DOI

ISSN

2076-393X

Publication Date

June 6, 2020

Volume

8

Issue

2

Location

Switzerland

Related Subject Headings

  • 3207 Medical microbiology
  • 3204 Immunology
  • 3202 Clinical sciences