Broad heparin-binding haemagglutinin-specific cytokine and chemokine response in infants following Mycobacterium bovis BCG vaccination.
Heparin-binding haemagglutinin (HBHA)-specific immune responses have been linked to protection against tuberculosis (TB). We investigated the hypothesis that BCG vaccination of human infants primes an HBHA-specific response, using multiplex to measure secreted cytokines and chemokines following HBHA and Mycobacterium tuberculosis purified protein derivative (PPD) stimulation of diluted whole blood samples from BCG-vaccinated or -unvaccinated infants. Of 42 analytes measured, 24 and 32 significant, BCG-associated increases were detected in response to HBHA and PPD, respectively. Both response profiles included Th-1, Th-2, Th-17 and inflammatory cytokines and chemokines (e.g. IFN-γ, TNF-α, IL-5, IL-10, IL-13, IL-17, MIP-1α and MIP-1β). We also found that six of the seven responses most closely correlated with IFN-γ were common to both HBHA and PPD. Notably, all HBHA-specific secretion of cytokines and chemokines from infant samples was dependent on previous BCG vaccination. Also, long-term persistence of HBHA-specific responses was found in adolescents with evidence of infant BCG vaccination. This study demonstrates for the first time BCG priming of an HBHA-specific immune response in infants that is characterised by a broad cytokine and chemokine signature. It also suggests a number of BCG vaccination associated, HBHA-induced responses that should be useful for future studies of biomarkers of protection against TB.
Faculty of Infectious and Tropical Diseases, Department of Immunology and Infection, London School of Hygiene & Tropical Medicine, London, UK. steven.smith@lshtm.ac.uk
Steven G
SG
Smith
Sophie
S
Lecher
Rose
R
Blitz
Camille
C
Locht
Hazel M
HM
Dockrell
D000293:Adolescent; D000907:Antibodies, Bacterial / Q000276:immunology; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D054405:Chemokine CCL3 / Q000276:immunology; D054407:Chemokine CCL4 / Q000276:immunology; D018925:Chemokines / Q000276:immunology*; D015331:Cohort Studies; D006493:Heparin / Q000276:immunology*; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000276:immunology; D007378:Interleukins / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology*; D009163:Mycobacterium bovis / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology; D014373:Tuberculin / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000907:Antibodies, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines; C440647:HbhA protein, Mycobacterium tuberculosis; D007378:Interleukins; D008565:Membrane Proteins; D014373:Tuberculin; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D006493:Heparin