{"doi":"10.1126/sciimmunol.abl4102","title":"A clade C HIV-1 vaccine protects against heterologous SHIV infection by modulating IgG glycosylation and T helper response in macaques","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.","journal":"Science Immunology","year":2022,"id":274217,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.956,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":364798,"name":"Andrew Jones","orcid":"0000-0002-3739-2322","position":1,"is_corresponding":false},{"id":558767,"name":"Narayanaiah Cheedarla","orcid":"0000-0001-6072-4383","position":2,"is_corresponding":false},{"id":253811,"name":"Sailaja Gangadhara","orcid":"0000-0001-8603-628X","position":3,"is_corresponding":false},{"id":320206,"name":"Vicky Roy","orcid":"0000-0002-5064-1098","position":4,"is_corresponding":false},{"id":253812,"name":"Tiffany M. Styles","orcid":"0000-0002-0102-6566","position":5,"is_corresponding":false},{"id":559777,"name":"Ayalnesh Shiferaw","orcid":null,"position":6,"is_corresponding":false},{"id":253813,"name":"Korey A. Walter","orcid":"0000-0001-6353-5422","position":7,"is_corresponding":false},{"id":392397,"name":"LaTonya D. Williams","orcid":"0000-0001-8064-8533","position":8,"is_corresponding":false},{"id":332540,"name":"Xiaoying Shen","orcid":"0000-0002-8387-3952","position":9,"is_corresponding":false},{"id":230741,"name":"Gabriel Ozorowski","orcid":"0000-0002-9695-8138","position":10,"is_corresponding":false},{"id":285901,"name":"Wen-Hsin Lee","orcid":"0000-0001-9445-6671","position":11,"is_corresponding":false},{"id":256758,"name":"Samantha L. Burton","orcid":null,"position":12,"is_corresponding":false},{"id":434512,"name":"Yi Lasanajak","orcid":"0000-0003-1450-8107","position":13,"is_corresponding":false},{"id":373260,"name":"Xuezheng Song","orcid":"0000-0003-1751-2785","position":14,"is_corresponding":false},{"id":297202,"name":"Zhaohui Qin","orcid":"0000-0002-1583-146X","position":15,"is_corresponding":false},{"id":247224,"name":"Cynthia A. Derdeyn","orcid":"0000-0002-1220-513X","position":16,"is_corresponding":false},{"id":230082,"name":"Andrew B. Ward","orcid":"0000-0001-7153-3769","position":17,"is_corresponding":false},{"id":942291,"name":"John D. Clements","orcid":"0000-0001-5744-3249","position":18,"is_corresponding":false},{"id":424728,"name":"Raghavan Varadarajan","orcid":"0000-0002-0823-7577","position":19,"is_corresponding":false},{"id":258351,"name":"Georgia D. Tomaras","orcid":"0000-0001-8076-1931","position":20,"is_corresponding":false},{"id":253822,"name":"Pamela A. Kozlowski","orcid":"0000-0001-9906-6234","position":21,"is_corresponding":false},{"id":106757,"name":"Galit Alter","orcid":"0000-0002-7680-9215","position":22,"is_corresponding":false},{"id":253824,"name":"Rama Rao Amara","orcid":"0000-0002-6309-6797","position":23,"is_corresponding":false},{"id":558768,"name":"Anusmita Sahoo","orcid":"0000-0001-6903-969X","position":0,"is_corresponding":true}],"reference_count":97,"raw_metadata":null,"created_at":"2026-07-19T00:28:07.776043Z","pmid":"35867800","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}