Cervicovaginal Microbiome Diversity Does Not Alter Mucosal Pharmacokinetics of Systemically Delivered HIV Broadly Neutralizing Antibodies

Background: Broadly neutralizing antibodies (bNAbs) are a promising HIV prevention strategy due to their potent antiviral activity and potential for long-acting protection. While the vaginal microbiome can influence mucosal immunity and the efficacy of topical interventions, its effect on the pharmacokinetics of systemically administered bNAbs remains unclear. Methods: Forty-two women were included in a retrospective analysis of the CAPRISA 012B clinical trial evaluating passive immunization for HIV prevention. Vaginal microbiota were profiled using 16S rRNA gene sequencing and classified into three community state types (CSTs): CST I (Lactobacillus crispatus-dominated), CST III (Lactobacillus iners-dominated), and CST IV (diverse, non-Lactobacillus-dominated). Mucosal concentrations of CAP256V2LS were measured from Soft-cup cervicovaginal fluid using the Meso Scale Discovery (MSD) platform with electrochemiluminescence (ECL) detection. Longitudinal analyses assessed CST stability, transitions, and associations with mucosal antibody pharmacokinetics.