Exceptionally broad HIV-1 neutralization via bispecific antibody-mediated prepositioning.

ABSTRACT: Antibodies that recognize the conserved prehairpin intermediate (PHI) of class I viral membrane-fusion proteins typically show limited neutralization and have not been considered promising therapeutic agents. We previously developed a bispecific antibody (bsAb), iMab/D5_AR, directed toward both the gp41 N-heptad repeat (NHR) that is exposed within the HIV-1 PHI and toward CD4, the HIV-1 receptor on T cells. CD4-binding led to prepositioning of the bsAb at the site of viral fusion, enhancing its neutralization potency and achieving 95% breadth (IC80 < 5 μg/mL) against a panel of 119 pseudotyped, multiclade HIV-1 viruses. In the current study, we engineered a bsAb against NHR that also targets CCR5, one of two HIV-1 coreceptors on T cells. This optimized bsAb design further improves neutrali

SUBMITTER: Kim S 

PROVIDER: S-EPMC12519190 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature