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

Rakshit, Srabanti and Ahmed, Asma and Adiga, Vasista and Sundararaj, Bharath K and Sahoo, Pravat Nalini and Kenneth, John and D'Souza, George and Bonam, Wesley and Johnson, Christina and Franken, Kees L M C and Ottenhoff, Tom H M and Finak, Greg and Gottardo, Raphael and Stuart, Kenneth D and De Rosa, Stephen C and McElrath, M Juliana and Vyakarnam, Annapurna (2019) BCG revaccination boosts adaptive polyfunctional Th1/Th17 and innate effectors in IGRA(+) and IGRA(-) Indian adults. In: JCI INSIGHT, 4 (24).

Preview	PDF jic_ini_4-24_2019.pdf - Published Version Download (6MB) | Preview
Preview	PDF jci.insight.130540.sdcm.pdf - Published Supplemental Material Download (417kB) | Preview
Preview	PDF jci.insight.130540.sd.pdf - Published Supplemental Material Download (2MB) | Preview
	Microsoft Excel jci.insight.130540.sdd1.xlsx - Published Supplemental Material Download (18kB)

Abstract

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 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.

Item Type:	Journal Article
Publication:	JCI INSIGHT
Publisher:	AMER SOC CLINICAL INVESTIGATION INC
Additional Information:	Copyright of this article belongs to AMER SOC CLINICAL INVESTIGATION INC
Keywords:	MYCOBACTERIUM-TUBERCULOSIS INFECTION; CALMETTE-GUERIN REVACCINATION; SCHOOL-AGED CHILDREN; T-CELLS; NONTUBERCULOUS MYCOBACTERIA; IMMUNE-RESPONSES; DOUBLE-BLIND; VACCINE; PREVENTION; EFFICACY
Department/Centre:	Division of Biological Sciences > Centre for Infectious Disease Research
Date Deposited:	31 Jan 2020 10:42
Last Modified:	31 Jan 2020 10:42
URI:	http://eprints.iisc.ac.in/id/eprint/64331

Actions (login required)

View Item