Deconvoluting the interplay of innate and adaptive immunity in BCG-induced nonspecific and TB-specific host resistance DOI Open Access
Kerry L. Hilligan, Patricia A. Darrah, Robert A. Seder

и другие.

The Journal of Experimental Medicine, Год журнала: 2025, Номер 222(4)

Опубликована: Фев. 28, 2025

BCG is the oldest vaccine in continuous use. While current intradermal vaccination regimens confer limited protection outside context of pediatric extrapulmonary tuberculosis (TB), promising new data indicate that when administered mucosally or intravenously at a higher dose, can induce sterilizing immunity against pulmonary TB nonhuman primates. also known to promote nonspecific host resistance variety unrelated infections and standard immunotherapy for bladder cancer, suggesting this innate immune function may contribute its protective role TB. Here, we propose both mycobacterial-specific off-target effects depend on interplay adaptive cells cytokines they produce, elucidation interaction should be major strategy development more effective BCG-based vaccines immunotherapies.

Язык: Английский

Intravenous BCG-mediated protection against tuberculosis requires CD4+ T cells and CD8α+ lymphocytes DOI
Andrew Simonson, Joseph J. Zeppa, Allison N. Bucşan

и другие.

The Journal of Experimental Medicine, Год журнала: 2025, Номер 222(4)

Опубликована: Янв. 17, 2025

Tuberculosis (TB) is a major health burden worldwide despite widespread intradermal (ID) BCG vaccination in newborns. We previously demonstrated that changing the route and dose from 5 × 105 CFUs ID to 107 i.v. resulted prevention of Mycobacterium tuberculosis (Mtb) infection TB disease highly susceptible nonhuman primates. Identifying immune mechanisms protection following will facilitate development more effective vaccines against TB. Here, we depleted lymphocyte subsets prior during Mtb challenge BCG-vaccinated macaques identify those necessary for protection. Depletion adaptive CD4 T cells, but not CD8αβ loss with increased burdens dissemination, indicating cells are critical BCG-mediated unconventional CD8α-expressing lymphocytes (NK innate CD4+CD8α+ double-positive cells) abrogated most BCG-immunized macaques, supporting further investigation into which these cell contribute after vaccination.

Язык: Английский

Процитировано

1
Deconvoluting the interplay of innate and adaptive immunity in BCG-induced nonspecific and TB-specific host resistance DOI Open Access
Kerry L. Hilligan, Patricia A. Darrah, Robert A. Seder

и другие.

The Journal of Experimental Medicine, Год журнала: 2025, Номер 222(4)

Опубликована: Фев. 28, 2025

BCG is the oldest vaccine in continuous use. While current intradermal vaccination regimens confer limited protection outside context of pediatric extrapulmonary tuberculosis (TB), promising new data indicate that when administered mucosally or intravenously at a higher dose, can induce sterilizing immunity against pulmonary TB nonhuman primates. also known to promote nonspecific host resistance variety unrelated infections and standard immunotherapy for bladder cancer, suggesting this innate immune function may contribute its protective role TB. Here, we propose both mycobacterial-specific off-target effects depend on interplay adaptive cells cytokines they produce, elucidation interaction should be major strategy development more effective BCG-based vaccines immunotherapies.

Язык: Английский

Процитировано

0