Sahoo, A and Jones, AT and Cheedarla, N and Gangadhara, S and Roy, V and Styles, TM and Shiferaw, A and Walter, KL and Williams, LD and Shen, X and Ozorowski, G and Lee, W-H and Burton, S and Yi, L and Song, X and Qin, ZS and Derdeyn, CA and Ward, AB and Clements, JD and Varadarajan, R and Tomaras, GD and Kozlowski, PA and Alter, G and Amara, RR (2022) A clade C HIV-1 vaccine protects against heterologous SHIV infection by modulating IgG glycosylation and T helper response in macaques. In: Science immunology, 7 (73). eabl4102.
Full text not available from this repository.Abstract
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.
| Item Type: | Journal Article |
|---|---|
| Publication: | Science immunology |
| Publisher: | NLM (Medline) |
| Additional Information: | The copyright for this article belongs to the NLM (Medline). |
| Keywords: | Human immunodeficiency virus vaccine; immunoglobulin G; tumor necrosis factor, animal; CD8+ T lymphocyte; glycosylation; Human immunodeficiency virus 1; rhesus monkey; Simian immunodeficiency virus; Vaccinia virus, AIDS Vaccines; Animals; CD8-Positive T-Lymphocytes; Glycosylation; HIV-1; Immunoglobulin G; Macaca mulatta; Simian Immunodeficiency Virus; Tumor Necrosis Factor-alpha; Vaccinia virus |
| Department/Centre: | Division of Biological Sciences > Molecular Biophysics Unit |
| Date Deposited: | 23 Aug 2022 05:11 |
| Last Modified: | 23 Aug 2022 05:11 |
| URI: | https://eprints.iisc.ac.in/id/eprint/76153 |
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