A clade C HIV-1 vaccine protects against heterologous SHIV infection by modulating IgG glycosylation and T helper response in macaques.

Journal Article (Journal Article)

The rising global HIV-1 burden urgently requires vaccines capable of providing heterologous protection. Here, we developed a clade C HIV-1 vaccine consisting of priming with modified vaccinia Ankara (MVA) and boosting with cyclically permuted trimeric gp120 (CycP-gp120) protein, delivered either orally using a needle-free injector or through parenteral injection. We tested protective efficacy of the vaccine against intrarectal challenges with a pathogenic heterologous clade C SHIV infection in rhesus macaques. Both routes of vaccination induced a strong envelope-specific IgG in serum and rectal secretions directed against V1V2 scaffolds from a global panel of viruses with polyfunctional activities. Envelope-specific IgG showed lower fucosylation compared with total IgG at baseline, and most of the vaccine-induced proliferating blood CD4+ T cells did not express CCR5 and α4β7, markers associated with HIV target cells. After SHIV challenge, both routes of vaccination conferred significant and equivalent protection, with 40% of animals remaining uninfected at the end of six weekly repeated challenges with an estimated efficacy of 68% per exposure. Induction of envelope-specific IgG correlated positively with G1FB glycosylation, and G2S2F glycosylation correlated negatively with protection. Vaccine-induced TNF-α+ IFN-γ+ CD8+ T cells and TNF-α+ CD4+ T cells expressing low levels of CCR5 in the rectum at prechallenge were associated with decreased risk of SHIV acquisition. These results demonstrate that the clade C MVA/CycP-gp120 vaccine provides heterologous protection against a tier2 SHIV rectal challenge by inducing a polyfunctional antibody response with distinct Fc glycosylation profile, as well as cytotoxic CD8 T cell response and CCR5-negative T helper response in the rectum.

Full Text

Duke Authors

Cited Authors

  • Sahoo, A; Jones, AT; Cheedarla, N; Gangadhara, S; Roy, V; Styles, TM; Shiferaw, A; Walter, KL; Williams, LD; Shen, X; Ozorowski, G; Lee, W-H; Burton, S; Yi, L; Song, X; Qin, ZS; Derdeyn, CA; Ward, AB; Clements, JD; Varadarajan, R; Tomaras, GD; Kozlowski, PA; Alter, G; Amara, RR

Published Date

  • July 22, 2022

Published In

Volume / Issue

  • 7 / 73

Start / End Page

  • eabl4102 -

PubMed ID

  • 35867800

Pubmed Central ID

  • PMC9410801

Electronic International Standard Serial Number (EISSN)

  • 2470-9468

Digital Object Identifier (DOI)

  • 10.1126/sciimmunol.abl4102

Language

  • eng

Conference Location

  • United States