{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Brady JM"],"funding":["NIDA NIH HHS","NIAID NIH HHS"],"pagination":["eabn9662"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9507259"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(655)"],"pubmed_abstract":["HIV broadly neutralizing antibodies (bNAbs) are capable of both blocking viral entry and driving innate immune responses against HIV-infected cells through their Fc region. Vaccination or productive infection results in a polyclonal mixture of class-switched immunoglobulin G (IgG) antibodies composed of four subclasses, each encoding distinct Fc regions that differentially engage innate immune functions. Despite evidence that innate immunity contributes to protection, the relative contribution of individual IgG subclasses is unknown. Here, we used vectored immunoprophylaxis in humanized mice to interrogate the efficacy of individual IgG subclasses during prevention of vaginal HIV transmission by VRC07, a potent CD4-binding site-directed bNAb. We find that VRC07 IgG2, which lacks Fc-mediated functionality, exhibited substantially reduced protection in vivo relative to other subclasses. Low concentrations of highly functional VRC07 IgG1 yielded substantial protection against vaginal challenge, suggesting that interventions capable of eliciting modest titers of functional IgG subclasses may provide meaningful benefit against infection."],"journal":["Science translational medicine"],"pubmed_title":["Antibody-mediated prevention of vaginal HIV transmission is dictated by IgG subclass in humanized mice."],"pmcid":["PMC9507259"],"funding_grant_id":["DP2 DA040254","R01 AI131975","F31 AI131747","K22 AI102769"],"pubmed_authors":["Tanno S","Phelps M","Garcia-Beltran WF","Ackerman ME","Nitido A","Parsons D","Boutros CL","Brady JM","Natarajan H","Vrbanac VD","Balazs AB","MacDonald SW","Lam EC","Deal CE"],"additional_accession":[]},"is_claimable":false,"name":"Antibody-mediated prevention of vaginal HIV transmission is dictated by IgG subclass in humanized mice.","description":"HIV broadly neutralizing antibodies (bNAbs) are capable of both blocking viral entry and driving innate immune responses against HIV-infected cells through their Fc region. Vaccination or productive infection results in a polyclonal mixture of class-switched immunoglobulin G (IgG) antibodies composed of four subclasses, each encoding distinct Fc regions that differentially engage innate immune functions. Despite evidence that innate immunity contributes to protection, the relative contribution of individual IgG subclasses is unknown. Here, we used vectored immunoprophylaxis in humanized mice to interrogate the efficacy of individual IgG subclasses during prevention of vaginal HIV transmission by VRC07, a potent CD4-binding site-directed bNAb. We find that VRC07 IgG2, which lacks Fc-mediated functionality, exhibited substantially reduced protection in vivo relative to other subclasses. Low concentrations of highly functional VRC07 IgG1 yielded substantial protection against vaginal challenge, suggesting that interventions capable of eliciting modest titers of functional IgG subclasses may provide meaningful benefit against infection.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jul","modification":"2025-04-22T05:09:43.234Z","creation":"2025-02-19T00:41:58.769Z"},"accession":"S-EPMC9507259","cross_references":{"pubmed":["35895834"],"doi":["10.1126/scitranslmed.abn9662"]}}