Enhanced efficacy of BCG vaccine formulated in adjuvant is dependent on IL-17A expression - 05/09/24
Abstract |
A new, more effective vaccine against tuberculosis (TB) is urgently needed to curtail the current TB problem. The only licensed vaccine, BCG, has been shown to have highly variable protective efficacy in several clinical trials ranging from zero to 80 % against TB disease. We have previously reported that BCG formulated in dimethyl dioctadecyl-ammonium bromide (DDA) with D-(+)-Trehalose 6,6′-Dibehenate (TDB) adjuvant (BCG + Adj) is significantly more protective than BCG alone following murine aerosol Mycobacterium tuberculosis infection. Here we investigate the immunological basis for this improved efficacy by examining expression of different immune markers and cytokines in the lungs of vaccinated mice after M. tuberculosis aerosol challenge. We found significantly greater numbers of pulmonary IL-17A-expressing CD4+ T cells in mice immunized with BCG+Adj as compared to nonvaccinated and BCG-immunized mice at one-month post-challenge and that the enhanced protection was abrogated in IL-17A-deficient mice. Furthermore, we found significantly higher levels of IL-17A, IL-12p40 and IL-33 expression in the lungs of BCG + Adj immunized animals relative to nonvaccinated mice after M. tuberculosis challenge. These results demonstrate that the DDA/TDB adjuvant increases expression of IL-17A in response to the BCG vaccine and that these augmented IL-17A levels enhance control of M. tuberculosis infection.
Le texte complet de cet article est disponible en PDF.Highlights |
• | BCG formulated in DDA + TDB adjuvant is significantly more protective in mice against M. tuberculosis than BCG alone. |
• | BCG+Adj induces significantly greater numbers of lung CD4+ T cells expressing IL-17A post-infection than BCG alone. |
• | Enhanced protection provided by BCG+Adj is absent in IL-17A deficient mice, but the efficacy of BCG alone is unaffected. |
• | Post-challenge pulmonary IL-17A, IL-12p40 and IL-33 levels are significantly greater in the BCG+Adj group versus controls. |
Keywords : BCG, Adjuvant, Tuberculosis, Interleukin-17, Interleukin-33
Plan
Vol 148
Article 102540- septembre 2024 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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