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<p>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. 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 16&#xa0;S rRNA gene sequencing and classified into three community state types (CSTs): CST I (<i>Lactobacillus crispatus</i>-dominated), CST III (<i>Lactobacillus iners</i>-dominated), and CST IV (diverse, non-<i>Lactobacillus</i>-dominated). Mucosal concentrations of CAP256V2LS were measured from Soft-cup<sup>®</sup> 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. <i>Lactobacillus</i>-dominated CSTs were most frequent (CST I, 5.3%; CST III, 57.9%), whereas BV-associated CST IV subtypes were less common (CST IV-A, 2.6%; CST IV-B, 34.2%). <i>Lactobacillus</i>-dominated communities were generally stable, while high-diversity CST IV communities were more dynamic, with transitions toward <i>Lactobacillus</i>-dominated states observed over time. Despite these microbial shifts, mucosal bNAb kinetic patterns appeared broadly similar across CSTs. Within the limits of this exploratory analysis, we did not observe clear evidence of an association between CST composition and the timing or magnitude of mucosal bNAb accumulation. These observations were descriptive and not derived from inferential statistical or pharmacokinetic modelling analyses. In this exploratory sub-analysis, cervicovaginal microbiome composition was not clearly associated with differences in mucosal concentrations of systemically administered bNAbs. These findings suggest that systemic bNAb delivery may achieve measurable genital tract exposure across diverse vaginal microbial communities; however, larger studies incorporating inferential pharmacokinetic and immunological analyses are needed to confirm these observations and exclude subtle microbiome-associated effects.</p>

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Cervicovaginal microbiome diversity was not associated with mucosal pharmacokinetics of systemically delivered HIV broadly neutralizing antibodies

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月19日

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  • Andile Mtshali,
  • Amadou Hamidou Togo,
  • Asavela Kama,
  • Marothi Letsoalo,
  • Gugulethu Mzobe,
  • Aida Sivro,
  • Nigel Garrett,
  • Nomusa Zondo,
  • Sharana Mahomed,
  • Derseree Archary,
  • Sinaye Ngcapu

摘要

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. 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 16 S 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. Lactobacillus-dominated CSTs were most frequent (CST I, 5.3%; CST III, 57.9%), whereas BV-associated CST IV subtypes were less common (CST IV-A, 2.6%; CST IV-B, 34.2%). Lactobacillus-dominated communities were generally stable, while high-diversity CST IV communities were more dynamic, with transitions toward Lactobacillus-dominated states observed over time. Despite these microbial shifts, mucosal bNAb kinetic patterns appeared broadly similar across CSTs. Within the limits of this exploratory analysis, we did not observe clear evidence of an association between CST composition and the timing or magnitude of mucosal bNAb accumulation. These observations were descriptive and not derived from inferential statistical or pharmacokinetic modelling analyses. In this exploratory sub-analysis, cervicovaginal microbiome composition was not clearly associated with differences in mucosal concentrations of systemically administered bNAbs. These findings suggest that systemic bNAb delivery may achieve measurable genital tract exposure across diverse vaginal microbial communities; however, larger studies incorporating inferential pharmacokinetic and immunological analyses are needed to confirm these observations and exclude subtle microbiome-associated effects.