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Cooperation Between Systemic and Mucosal Antibodies Induced by Virosomal Vaccines Targeting HIV-1 Env: Protection of Indian Rhesus Macaques Against Low-Dose Intravaginal SHIV Challenges.

Authors :
Lakhashe SK
Amacker M
Hariraju D
Vyas HK
Morrison KS
Weiner JA
Ackerman ME
Roy V
Alter G
Ferrari G
Montefiori DC
Tomaras GD
Sawant S
Yates NL
Gast C
Fleury S
Ruprecht RM
Source :
Frontiers in immunology [Front Immunol] 2022 Feb 22; Vol. 13, pp. 788619. Date of Electronic Publication: 2022 Feb 22 (Print Publication: 2022).
Publication Year :
2022

Abstract

A virosomal vaccine inducing systemic/mucosal anti-HIV-1 gp41 IgG/IgA had previously protected Chinese-origin rhesus macaques (RMs) against vaginal SHIV <subscript>SF162P3</subscript> challenges. Here, we assessed its efficacy in Indian-origin RMs by intramuscular priming/intranasal boosting (n=12/group). Group K received virosome-P1-peptide alone (harboring the Membrane Proximal External Region), Group L combined virosome-rgp41 plus virosome-P1, and Group M placebo virosomes. Vaccination induced plasma binding but no neutralizing antibodies. Five weeks after boosting, all RMs were challenged intravaginally with low-dose SHIV <subscript>SF162P3</subscript> until persistent systemic infection developed. After SHIV challenge #7, six controls were persistently infected versus only one Group L animal (vaccine efficacy 87%; P =0.0319); Group K was not protected. After a 50% SHIV dose increase starting with challenge #8, protection in Group L was lost. Plasmas/sera were analyzed for IgG phenotypes and effector functions; the former revealed that protection in Group L was significantly associated with increased binding to FcγR2/3(A/B) across several time-points, as were some IgG measurements. Vaginal washes contained low-level anti-gp41 IgGs and IgAs, representing a 1-to-5-fold excess over the SHIV inoculum's gp41 content, possibly explaining loss of protection after the increase in challenge-virus dose. Virosomal gp41-vaccine efficacy was confirmed during the initial seven SHIV challenges in Indian-origin RMs when the SHIV inoculum had at least 100-fold more HIV RNA than acutely infected men's semen. Vaccine protection by virosome-induced IgG and IgA parallels the cooperation between systemically administered IgG1 and mucosally applied dimeric IgA2 monoclonal antibodies that as single-agents provided no/low protection - but when combined, prevented mucosal SHIV transmission in all passively immunized RMs.<br />Competing Interests: MA and SF are employees of Mymetics SA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2022 Lakhashe, Amacker, Hariraju, Vyas, Morrison, Weiner, Ackerman, Roy, Alter, Ferrari, Montefiori, Tomaras, Sawant, Yates, Gast, Fleury and Ruprecht.)

Details

Language :
English
ISSN :
1664-3224
Volume :
13
Database :
MEDLINE
Journal :
Frontiers in immunology
Publication Type :
Academic Journal
Accession number :
35273592
Full Text :
https://doi.org/10.3389/fimmu.2022.788619