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

Détails

ID Serval
serval:BIB_912C7148B907
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
BCG revaccination boosts adaptive polyfunctional Th1/Th17 and innate effectors in IGRA+ and IGRA- Indian adults.
Périodique
JCI insight
Auteur⸱e⸱s
Rakshit S., Ahmed A., Adiga V., Sundararaj B.K., Sahoo P.N., Kenneth J., D'Souza G., Bonam W., Johnson C., Franken K.L., Ottenhoff T.H., Finak G., Gottardo R., Stuart K.D., De Rosa S.C., McElrath M.J., Vyakarnam A.
ISSN
2379-3708 (Electronic)
ISSN-L
2379-3708
Statut éditorial
Publié
Date de publication
19/12/2019
Peer-reviewed
Oui
Volume
4
Numéro
24
Langue
anglais
Notes
Publication types: Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
BACKGROUNDBacille Calmette-Guérin (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.METHODSTwo hundred healthy adults, BCG vaccinated at birth, were tested for their IFN-γ 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.RESULTSIFN-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 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-γ+ NK/γδ/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.CONCLUSIONThese 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.FUNDINGThis work was funded principally by DBT-NIH (BT/MB/Indo-US/HIPC/2013).
Mots-clé
Adolescent, Adult, Antigens, Bacterial/administration & dosage, Antigens, Bacterial/immunology, BCG Vaccine/administration & dosage, BCG Vaccine/immunology, Endemic Diseases/prevention & control, Female, Healthy Volunteers, Humans, Immunity, Innate, Immunization, Secondary, Immunogenicity, Vaccine, India, Interferon-gamma Release Tests/statistics & numerical data, Mycobacterium tuberculosis/immunology, Prospective Studies, Th1 Cells/immunology, Th17 Cells/immunology, Treatment Outcome, Tuberculosis/immunology, Tuberculosis/microbiology, Tuberculosis/prevention & control, Young Adult, Adaptive immunity, Immunology, Infectious disease, Innate immunity, Tuberculosis
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/02/2022 11:45
Dernière modification de la notice
23/03/2024 7:24
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