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Rakshit, S.; Ahmed, A.; Adiga, V.; Sundararaj, B.K.; Sahoo, P.N.; Kenneth, J.; ... ; Vyakarnam, A. (2019)

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

Article / Letter to editor
BACKGROUND. Bacille Calmette-Guerin (BCG) vaccine is protective against Tuberculosis (TB) 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. Two hundred healthy adults, BCG vaccinated at birth, were tested for their IFN-gamma release assay (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-color flow cytometry over 34 weeks.RESULTS. IFN-gamma 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 with IGRA- vaccinees. Polyfunctional Ag85A, BCG, and mycobacterium tuberculosis (Mtb) latency Ag-specific (LTAg-specific) CD4(+) T cells expressing up to 8 cytokines were also...Show moreBACKGROUND. Bacille Calmette-Guerin (BCG) vaccine is protective against Tuberculosis (TB) 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. Two hundred healthy adults, BCG vaccinated at birth, were tested for their IFN-gamma release assay (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-color flow cytometry over 34 weeks.RESULTS. IFN-gamma 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 with IGRA- vaccinees. Polyfunctional Ag85A, BCG, and mycobacterium tuberculosis (Mtb) latency Ag-specific (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 focused 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-gamma(+) NK/gamma delta/NKT cell responses were higher in both IGRA(+) and IGRA- vaccinees compared with controls. This is the first evidence to our knowledge that BCG revaccination significantly boosts antimycobacterial Th1/Th17 responses in IGRA(+) and IGRA- subjects.CONCLUSION. These data show that BCG revaccination is immunogenic in IGRA- and IGRA(+) subjects, implying that Mtb preinfection in IGRA(+) subjects does not impact immunogenicity. This has implications for public health and vaccine development strategies.Show less
All authors
Rakshit, S.; Ahmed, A.; Adiga, V.; Sundararaj, B.K.; Sahoo, P.N.; Kenneth, J.; D'Souza, G.; Bonam, W.; Johnson, C.; Franken, K.L.M.C.; Ottenhoff, T.H.M.; Finak, G.; Gottardo, R.; Stuart, K.D.; Rosa, S.C. de; McElrath, M.J.; Vyakarnam, A.
Date
2019-12-19
Journal
JCI Insight
Volume
4
Issue
24
DOI
doi:10.1172/jci.insight.130540