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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.

Publication ,  Journal Article
Lakhashe, SK; Amacker, M; Hariraju, D; Vyas, HK; Morrison, KS; Weiner, JA; Ackerman, ME; Roy, V; Alter, G; Ferrari, G; Montefiori, DC; Gast, C ...
Published in: Front Immunol
2022

A virosomal vaccine inducing systemic/mucosal anti-HIV-1 gp41 IgG/IgA had previously protected Chinese-origin rhesus macaques (RMs) against vaginal SHIVSF162P3 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 SHIVSF162P3 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.

Duke Scholars

Published In

Front Immunol

DOI

EISSN

1664-3224

Publication Date

2022

Volume

13

Start / End Page

788619

Location

Switzerland

Related Subject Headings

  • Virosomes
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Macaca mulatta
  • Immunoglobulin G
  • Immunoglobulin A
  • Humans
  • HIV-1
  • HIV Seropositivity
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lakhashe, S. K., Amacker, M., Hariraju, D., Vyas, H. K., Morrison, K. S., Weiner, J. A., … Ruprecht, R. M. (2022). 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. Front Immunol, 13, 788619. https://doi.org/10.3389/fimmu.2022.788619

Published In

Front Immunol

DOI

EISSN

1664-3224

Publication Date

2022

Volume

13

Start / End Page

788619

Location

Switzerland

Related Subject Headings

  • Virosomes
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Macaca mulatta
  • Immunoglobulin G
  • Immunoglobulin A
  • Humans
  • HIV-1
  • HIV Seropositivity
  • Female