Vaccination with Immune Complexes Modulates the Elicitation of Functional Antibodies Against HIV-1

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Oct 19

PMID 37854587

Authors

Catarina E Hioe

Xiaomei Liu

Andrew N Banin

Daniel W Heindel

Jeromine Klingler

Priyanka G Rao

Christina C Luo

Xunqing Jiang

Shilpi Pandey

Tracy Ordonez

Philip Barnette

Maxim Totrov

Jiang Zhu

Arthur Nadas

Susan Zolla-Pazner

Chitra Upadhyay

Xiaoying Shen

Xiang-Peng Kong

Ann J Hessell

Affiliations

Soon will be listed here.

Abstract

Introduction: Neutralizing 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.

Objective: This study sought to test vaccines aimed to induce Abs against neutralizing epitopes at the V1V2 apex of HIV-1 envelope (Env).

Methods: Four 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 .

Results: Rabbit 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.

Conclusion: These 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.

Citing Articles

Signal peptide exchange alters HIV-1 envelope antigenicity and immunogenicity.

Upadhyay C, Rao P, Behzadi M, Feyznezhad R, Lambert G, Kumar R Front Immunol. 2024; 15():1476924.

PMID: 39380992 PMC: 11458420. DOI: 10.3389/fimmu.2024.1476924.

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