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

Publication ,  Journal Article
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 ...
Published in: Sci Immunol
July 22, 2022

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.

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Published In

Sci Immunol

DOI

EISSN

2470-9468

Publication Date

July 22, 2022

Volume

7

Issue

73

Start / End Page

eabl4102

Location

United States

Related Subject Headings

  • Vaccinia virus
  • Tumor Necrosis Factor-alpha
  • T-Lymphocytes, Helper-Inducer
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Macaca mulatta
  • Immunoglobulin G
  • HIV-1
  • Glycosylation
  • CD8-Positive T-Lymphocytes
 

Citation

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ICMJE
MLA
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Sahoo, A., Jones, A. T., Cheedarla, N., Gangadhara, S., Roy, V., Styles, T. M., … Amara, R. R. (2022). A clade C HIV-1 vaccine protects against heterologous SHIV infection by modulating IgG glycosylation and T helper response in macaques. Sci Immunol, 7(73), eabl4102. https://doi.org/10.1126/sciimmunol.abl4102
Sahoo, Anusmita, Andrew T. Jones, Narayanaiah Cheedarla, Sailaja Gangadhara, Vicky Roy, Tiffany M. Styles, Ayalnesh Shiferaw, et al. “A clade C HIV-1 vaccine protects against heterologous SHIV infection by modulating IgG glycosylation and T helper response in macaques.Sci Immunol 7, no. 73 (July 22, 2022): eabl4102. https://doi.org/10.1126/sciimmunol.abl4102.
Sahoo A, Jones AT, Cheedarla N, Gangadhara S, Roy V, Styles TM, et al. A clade C HIV-1 vaccine protects against heterologous SHIV infection by modulating IgG glycosylation and T helper response in macaques. Sci Immunol. 2022 Jul 22;7(73):eabl4102.
Sahoo, Anusmita, et al. “A clade C HIV-1 vaccine protects against heterologous SHIV infection by modulating IgG glycosylation and T helper response in macaques.Sci Immunol, vol. 7, no. 73, July 2022, p. eabl4102. Pubmed, doi:10.1126/sciimmunol.abl4102.
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. A clade C HIV-1 vaccine protects against heterologous SHIV infection by modulating IgG glycosylation and T helper response in macaques. Sci Immunol. 2022 Jul 22;7(73):eabl4102.

Published In

Sci Immunol

DOI

EISSN

2470-9468

Publication Date

July 22, 2022

Volume

7

Issue

73

Start / End Page

eabl4102

Location

United States

Related Subject Headings

  • Vaccinia virus
  • Tumor Necrosis Factor-alpha
  • T-Lymphocytes, Helper-Inducer
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Macaca mulatta
  • Immunoglobulin G
  • HIV-1
  • Glycosylation
  • CD8-Positive T-Lymphocytes