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

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Srabanti Rakshit, Asma Ahmed, Vasista Adiga, Bharath K Sundararaj, Pravat Nalini Sahoo, John Kenneth, George D'Souza, Wesley Bonam, Christina Johnson, Kees Lmc Franken, Tom Hm Ottenhoff, Greg Finak, Raphael Gottardo, Kenneth D Stuart, Stephen C De Rosa, M Juliana McElrath, Annapurna Vyakarnam

Original languageEnglish
JournalJCI Insight
Early online date19 Nov 2019
Publication statusPublished - 2019

King's Authors


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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