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
Institution
Titre
BCG revaccination boosts adaptive polyfunctional Th1/Th17 and innate effectors in IGRA+ and IGRA- Indian adults.
Périodique
JCI insight
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
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