BCG vaccination recalibrates innate immunity in ART-treated people with HIV
- 1University Hospital Zurich
Abstract
Despite suppressive antiretroviral therapy, many people with HIV (PWH) retain chronic interferon-associated immune dysregulation. Observational data from the Swiss HIV Cohort Study linked asymptomatic mycobacterial exposure to lower viral set points, reduced interferon-associated activity, and attenuated HIV-specific antibody responses, a pattern sharing features with HIV elite controllers and natural hosts of primate lentiviruses. We therefore examined whether Bacillus Calmette-Guerin (BCG) vaccination could induce a related immune configuration in ART-treated PWH. Using longitudinal systems-level profiling within the BELIEVE trial, we found that BCG reduced constitutive NK cell IFN-{gamma} production and PBMC-mediated direct cytotoxicity without impairing inducible cytokine responses or antibody-dependent cellular cytotoxicity. Multiomic and proteomic analyses showed reduced interferon- and activation-associated programs, while adaptive immune parameters remained largely stable and follow-up revealed no obvious adverse clinical pattern. This configuration, reduced baseline interferon activity coexisting with preserved Fc-dependent effector function, shares selected features with immune states described in natural lentiviral control and provides a rationale for testing BCG in combination with antibody-based HIV interventions.
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BibTeX
@misc{dolle2026vaccination,
title = {{BCG vaccination recalibrates innate immunity in ART-treated people with HIV}},
author = {C. Dolle and T. K. Tutumlu and L. Bartl and B. Depouilly and D. Russenberger and M. Zeeb and K. Kusejko and E. West and D. L. Braun and M. Schwarzmüller and B. Elie and A. Trkola and H. F. Günthard and J. Nemeth},
howpublished = {medRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.28.26361620},
url = {https://www.medrxiv.org/content/10.64898/2026.08.28.26361620v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - BCG vaccination recalibrates innate immunity in ART-treated people with HIV
AU - C. Dolle
AU - T. K. Tutumlu
AU - L. Bartl
AU - B. Depouilly
AU - D. Russenberger
AU - M. Zeeb
AU - K. Kusejko
AU - E. West
AU - D. L. Braun
AU - M. Schwarzmüller
AU - B. Elie
AU - A. Trkola
AU - H. F. Günthard
AU - J. Nemeth
PY - 2026
DA - 2026/08/28
PB - medRxiv
DO - 10.64898/2026.08.28.26361620
UR - https://www.medrxiv.org/content/10.64898/2026.08.28.26361620v1
AB - Despite suppressive antiretroviral therapy, many people with HIV (PWH) retain chronic interferon-associated immune dysregulation. Observational data from the Swiss HIV Cohort Study linked asymptomatic mycobacterial exposure to lower viral set points, reduced interferon-associated activity, and attenuated HIV-specific antibody responses, a pattern sharing features with HIV elite controllers and natural hosts of primate lentiviruses. We therefore examined whether Bacillus Calmette-Guerin (BCG) vaccination could induce a related immune configuration in ART-treated PWH. Using longitudinal systems-level profiling within the BELIEVE trial, we found that BCG reduced constitutive NK cell IFN-{gamma} production and PBMC-mediated direct cytotoxicity without impairing inducible cytokine responses or antibody-dependent cellular cytotoxicity. Multiomic and proteomic analyses showed reduced interferon- and activation-associated programs, while adaptive immune parameters remained largely stable and follow-up revealed no obvious adverse clinical pattern. This configuration, reduced baseline interferon activity coexisting with preserved Fc-dependent effector function, shares selected features with immune states described in natural lentiviral control and provides a rationale for testing BCG in combination with antibody-based HIV interventions.
ER -