Vaccination with immune complexes modulates the elicitation of functional antibodies against HIV-1

Frontiers in Immunology

Immunology

Christina C. Luo¹  Xiang-Peng Kong¹  Xunqing Jiang¹  Arthur Nádas²  Jiang Zhu³  Priyanka G. Rao⁴  Susan Zolla-Pazner⁴  Xiaomei Liu⁴  Daniel W. Heindel⁴  Andrew N. Banin⁴  Jéromine Klingler⁴  Chitra Upadhyay⁴  Catarina E. Hioe⁵  Shilpi Pandey⁶  Ann J. Hessell⁶  Philip Barnette⁶  Tracy Ordonez⁶  Xiaoying Shen⁷  Maxim Totrov⁸ 

[1] Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY, United States;Department of Environment Medicine, New York University Grossman School of Medicine, New York, NY, United States;Department of Integrative Structural and Computational Biology and Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, United States;Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States;Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States;Research Service, James J. Peters VA Medical Center, Bronx, NY, United States;Division of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United States;Division of Surgical Sciences, Department of Surgery, Duke University School of Medicine, Durham, NC, United States;Molsoft L.L.C., San Diego, CA, United States;

关键词: HIV-1 vaccine;    HIV-1 Env;    antibody;    immune complex (IC);    virus neutralization;    ADCP;   

DOI  :  10.3389/fimmu.2023.1271686

 received in 2023-08-02, accepted in 2023-09-05,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionNeutralizing antibodies (Abs) are one of the immune components required to protect against viral infections. However, developing vaccines capable of eliciting neutralizing Abs effective against a broad array of HIV-1 isolates has been an arduous challenge.ObjectiveThis study sought to test vaccines aimed to induce Abs against neutralizing epitopes at the V1V2 apex of HIV-1 envelope (Env).MethodsFour groups of rabbits received a DNA vaccine expressing the V1V2 domain of the CRF01_AE A244 strain on a trimeric 2J9C scaffold (V1V2-2J9C) along with a protein vaccine consisting of an uncleaved prefusion-optimized A244 Env trimer with V3 truncation (UFO-BG.ΔV3) or a V1V2-2J9C protein and their respective immune complexes (ICs). These IC vaccines were made using 2158, a V1V2-specific monoclonal Ab (mAb), which binds the V2i epitope in the underbelly region of V1V2 while allosterically promoting the binding of broadly neutralizing mAb PG9 to its V2 apex epitope in vitro.ResultsRabbit groups immunized with the DNA vaccine and uncomplexed or complexed UFO-BG.ΔV3 proteins (DNA/UFO-UC or IC) displayed similar profiles of Env- and V1V2-binding Abs but differed from the rabbits receiving the DNA vaccine and uncomplexed or complexed V1V2-2J9C proteins (DNA/V1V2-UC or IC), which generated more cross-reactive V1V2 Abs without detectable binding to gp120 or gp140 Env. Notably, the DNA/UFO-UC vaccine elicited neutralizing Abs against some heterologous tier 1 and tier 2 viruses from different clades, albeit at low titers and only in a fraction of animals, whereas the DNA/V1V2-UC or IC vaccines did not. In comparison with the DNA/UFO-UC group, the DNA/UFO-IC group showed a trend of higher neutralization against TH023.6 and a greater potency of V1V2-specific Ab-dependent cellular phagocytosis (ADCP) but failed to neutralize heterologous viruses.ConclusionThese data demonstrate the capacity of V1V2-2J9C-encoding DNA vaccine in combination with UFO-BG.ΔV3, but not V1V2-2J9C, protein vaccines, to elicit homologous and heterologous neutralizing activities in rabbits. The elicitation of neutralizing and ADCP activities was modulated by delivery of UFO-BG.ΔV3 complexed with V2i mAb 2158.

【 授权许可】

Unknown   
Copyright © 2023 Hioe, Liu, Banin, Heindel, Klingler, Rao, Luo, Jiang, Pandey, Ordonez, Barnette, Totrov, Zhu, Nádas, Zolla-Pazner, Upadhyay, Shen, Kong and Hessell