BCG revaccination boosts adaptive polyfunctional Th1/Th17 and innate effectors in IGRA⁺ and IGRA^- Indian adults

Background: Bacille Calmette-Guérin (BCG) vaccine is protective in children but its efficacy wanes with age. Consequently, determining if BCG revaccination augments anti-TB immunity in young adults in TB endemic regions is vital.

Methods: 200 healthy adults, BCG vaccinated at birth were tested for their IGRA status. Of these, 28 IGRA⁺ and 30 IGRA^- were BCG revaccinated and 24 IGRA⁺ and 23 IGRA^- subjects served as unvaccinated controls. T and innate cell responses to mycobacterial antigens were analyzed by 14-colour flow cytometry over 34 weeks.

Results: IFN-γ and/or IL-2 Ag85A and BCG-specific CD4⁺ and CD8⁺ T-cell responses were boosted by revacciantion at 4 and 34 weeks respectively and were >2-fold higher in IGRA⁺ compared to IGRA^- vaccinees. Polyfunctional Ag85A, BCG and Mtb latency Ag (LTAg)-specific CD4⁺ T-cells expressing up to 8 cytokines were also significantly enhanced in both IGRA⁺ and IGRA^- vaccinees relative to unvaccinated controls, most markedly in IGRA⁺ vaccinees. A focussed analysis of Th17 responses revealed expansion of Ag85A, BCG and LTAg-specific total IL-17A⁺IL-17F⁺IL-22⁺ and IL-10⁺ CD4⁺ T-cell effectors in both IGRA⁺ and IGRA^- subjects. Also, innate IFN-γ⁺ NK/γδ/NKT responses were higher in both IGRA⁺ and IGRA^- vaccinees compared to controls. This is the first evidence that BCG revaccination significantly boosts anti-mycobacterial Th1/Th17 responses in IGRA⁺ and IGRA^- subjects.

Summary: These data show that BCG revaccination is immunogenic in IGRA^- and IGRA⁺ subjects implying that Mtb pre-infection in IGRA⁺ subjects does not impact immunogenicity. This has implications for public health and vaccine development strategies.

Funding: This work was funded principally by DBT-NIH (BT/MB/Indo-US/HIPC/2013).

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