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- Title
Antibody-mediated prevention of vaginal HIV transmission is dictated by IgG subclass in humanized mice.
- Authors
Brady, Jacqueline M.; Phelps, Meredith; MacDonald, Scott W.; Lam, Evan C.; Nitido, Adam; Parsons, Dylan; Boutros, Christine L.; Deal, Cailin E.; Garcia-Beltran, Wilfredo F.; Tanno, Serah; Natarajan, Harini; Ackerman, Margaret E.; Vrbanac, Vladimir D.; Balazs, Alejandro B.
- 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. Characterizing classes: Understanding the role of IgG subclasses in protecting against HIV infection is essential for developing the most effective antibody therapeutics. Here, Brady et al. tested the impact of changing IgG subclasses on protection conferred by the broadly neutralizing antibody, VRC07. VRC07 IgG2 exhibited reduced protection as compared to other IgG subclasses, whereas even low concentrations of VRC07 IgG1 conferred protection against vaginal challenge with HIV in humanized mice. These results suggest that, for some broadly neutralizing antibodies, IgG subclass considerably influences protection.
- Subjects
HIV infection transmission; HIV prevention; HIV infections; IMMUNOGLOBULIN G; NATURAL immunity; MATERNAL-fetal exchange; IMMUNE response
- Publication
Science Translational Medicine, 2022, Vol 14, Issue 655, p1
- ISSN
1946-6234
- Publication type
Article
- DOI
10.1126/scitranslmed.abn9662