iScience (Dec 2024)

Humoral correlates of protection against Mycobacterium tuberculosis following intravenous BCG vaccination in rhesus macaques

  • Edward B. Irvine,
  • Patricia A. Darrah,
  • Shu Wang,
  • Chuangqi Wang,
  • Ryan P. McNamara,
  • Mario Roederer,
  • Robert A. Seder,
  • Douglas A. Lauffenburger,
  • JoAnne L. Flynn,
  • Sarah M. Fortune,
  • Galit Alter

Journal volume & issue
Vol. 27, no. 12
p. 111128

Abstract

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Summary: Altering Bacille Calmette-Guérin (BCG) immunization from low-dose intradermal (i.d.) to high-dose intravenous (i.v.) vaccination provides a high level of protection against Mycobacterium tuberculosis (Mtb). In addition to strong T cell immunity, i.v. BCG drives robust humoral immune responses that track with bacterial control. However, given the near-complete protection afforded by high-dose i.v. BCG immunization, a precise correlate of protection was difficult to define. Here we leveraged plasma and bronchoalveolar lavage fluid (BAL) from a cohort of rhesus macaques that received decreasing doses of i.v. BCG and aimed to define correlates of immunity following Mtb challenge. We show an i.v. BCG dose-dependent induction of mycobacterial-specific humoral immune responses. Antibody responses at peak immunogenicity predicted bacterial control post-challenge. Multivariate analyses revealed antibody-mediated complement and natural killer (NK) cell-activating humoral networks as key signatures of protective immunity. This work extends our understanding of humoral biomarkers and potential mechanisms of i.v. BCG-mediated protection against Mtb.

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