Do successful tuberculosis vaccines need to be immunoregulatory rather than merely Th1-boosting?
Tuberculosis vaccine candidates are entering clinical studies in areas where BCG fails. This is a high-risk strategy. We suggest that geographical variation in the efficacy of BCG is related to the presence in developing countries of a cross-reactive background Th2-like response, probably attributable to exposure of mother and infant to helminths and environmental mycobacteria. Such Th2-like activity can stop Mycobacterium tuberculosis from being pushed into a latent state by the Th1 response, impair bactericidal functions and cause toxicity of TNF-alpha and pulmonary fibrosis. A successful vaccine, rather than driving a Th1 response, might need to suppress this pre-existing subversive Th2-like component.
Rook
Graham A W
GA
Centre for Infectious Disease and International Health, University College London, Windeyer Institute of Medical Sciences, London W1T 4JF, UK. g.rook@ucl.ac.uk
Dheda
Keertan
K
Zumla
Alimuddin
A
D000818:Animals; D001500:BCG Vaccine / Q000276:immunology / Q000494:pharmacology; D003906:Developing Countries; D006801:Humans; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018448:Models, Immunological; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000472:pathogenicity; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D017211:Treatment Failure; D032581:Tuberculosis Vaccines / Q000276:immunology / Q000494:pharmacology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000401:mortality / Q000517:prevention & control
D001500:BCG Vaccine; D032581:Tuberculosis Vaccines; D015847:Interleukin-4