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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\n            <jats:sup>+<\/jats:sup>\n            T cells did not express CCR5 and \u03b14\u03b27, 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-\u03b1\n            <jats:sup>+<\/jats:sup>\n            IFN-\u03b3\n            <jats:sup>+<\/jats:sup>\n            CD8\n            <jats:sup>+<\/jats:sup>\n            T cells and TNF-\u03b1\n            <jats:sup>+<\/jats:sup>\n            CD4\n            <jats:sup>+<\/jats:sup>\n            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.\n          <\/jats:p>","DOI":"10.1126\/sciimmunol.abl4102","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T17:58:33Z","timestamp":1658512713000},"source":"Crossref","is-referenced-by-count":11,"title":["A clade C HIV-1 vaccine protects against heterologous SHIV infection by modulating IgG glycosylation and T helper response in macaques"],"prefix":"10.1126","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6903-969X","authenticated-orcid":true,"given":"Anusmita","family":"Sahoo","sequence":"first","affiliation":[{"name":"Emory Vaccine Center, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, 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