AI Article Synopsis
- High-dose intravenous (IV) BCG vaccination offers significant protection against infection, leading to insights into immune responses and mechanisms.
- IV BCG is linked to strong T cell immunity and enhanced humoral responses that correlate with effective bacterial control.
- Analysis of immune responses in rhesus macaques indicates that specific antibody responses are crucial for predicting bacterial control and highlight key immune networks involved in protection.
Article Abstract
Altering the route of Bacille Calmette-Guérin (BCG) immunization from low-dose intradermal vaccination to high-dose intravenous (IV) vaccination resulted in a high level of protection against ( ) infection, providing an opportunity to uncover immune correlates and mechanisms of protection. In addition to strong T cell immunity, IV BCG vaccination was associated with a robust expansion of humoral immune responses that tracked with bacterial control. However, given the near complete protection afforded by high-dose IV BCG immunization, a precise correlate of immune 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 IV BCG and aimed to define the correlates of immunity across macaques that experienced immune protection or breakthrough infection following challenge. We show an IV BCG dose-dependent induction of mycobacterial-specific humoral immune responses, both in the plasma and in the airways. Moreover, antibody responses at peak immunogenicity significantly predicted bacterial control following challenge. Multivariate analyses revealed antibody-mediated complement and NK cell activating humoral networks as key functional signatures associated with protective immunity. Collectively, this work extends our understanding of humoral biomarkers and potential mechanisms of IV BCG mediated protection against .
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418074 | PMC |
| http://dx.doi.org/10.1101/2023.07.31.551245 | DOI Listing |
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