{"doi":"10.3389/fimmu.2022.983313","title":"Multi-trial analysis of HIV-1 envelope gp41-reactive antibodies among global recipients of candidate HIV-1 vaccines","abstract":"Many participants in HIV-1 vaccine trials, who have not previously been exposed to or vaccinated against HIV-1, display serum immunoglobulin antibodies that bind the gp41 region of HIV-1 envelope prior to vaccination. Previous studies have hypothesized that these pre-existing antibodies may be cross-reactive and may skew future vaccine responses. In 12 large studies conducted by the HIV Vaccine Trial Network (HVTN) (n=1470 individuals), we find wide variation among participants in the pre-vaccine levels of gp41-reactive antibodies as measured by the binding antibody multiplex assay (BAMA). In the absence of exposure to the gp41 immunogen, anti-gp41 IgG levels were temporally stable over 26-52 weeks in repeated measures of placebo recipients. The analysis revealed that the geometric mean of pre-vaccine anti-gp41 IgG response was greater among participants in South Africa compared with participants in the United States. With gene-level metagenomic sequencing of pre-vaccination fecal samples collected from participants in one trial (HVTN 106), we detected positive associations between pre-vaccine anti-gp41 IgG and abundance of genes from multiple taxa in the Eubacteriales order. The genes most strongly associated with higher baseline anti-gp41 IgG mapped to a clade containing Blautia wexlerae and closely related strains. In trials with vaccine products containing the full or partial portion of gp41 immunogen alongside a gp120 immunogen, we did not find evidence that individuals with higher baseline anti-gp41 IgG had different levels of anti-gp120 IgG after vaccination compared to individuals with lower pre-vaccine anti-gp41 levels (pooled estimate of standardized mean difference -0.01 with a 95% CI [-0.37; 0.34]).","journal":"Frontiers in Immunology","year":2022,"id":284129,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9573,"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":961404,"name":"Andrew M. Johnson","orcid":"0000-0002-7269-3016","position":1,"is_corresponding":false},{"id":961405,"name":"Nicole Potchen","orcid":"0000-0003-0699-8863","position":2,"is_corresponding":false},{"id":961880,"name":"Simon S. Minot","orcid":null,"position":3,"is_corresponding":false},{"id":420013,"name":"Jack Heptinstall","orcid":"0000-0002-3401-5935","position":4,"is_corresponding":false},{"id":300922,"name":"Kelly E. Seaton","orcid":"0000-0002-2009-3270","position":5,"is_corresponding":false},{"id":258348,"name":"Sheetal Sawant","orcid":"0000-0002-1109-7907","position":6,"is_corresponding":false},{"id":332540,"name":"Xiaoying Shen","orcid":"0000-0002-8387-3952","position":7,"is_corresponding":false},{"id":258351,"name":"Georgia D. Tomaras","orcid":"0000-0001-8076-1931","position":8,"is_corresponding":false},{"id":302714,"name":"Andrew Fioré-Gartland","orcid":"0000-0001-7627-2166","position":9,"is_corresponding":false},{"id":288612,"name":"James G. Kublin","orcid":"0000-0003-1279-3741","position":10,"is_corresponding":false},{"id":382631,"name":"Koshlan Mayer-Blackwell","orcid":"0000-0002-1652-4023","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-19T00:29:32.702533Z","pmid":"36311720","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":[]}