Could the Risk of Asthma and Atopy Be Reduced by a Vaccine That Induces a Strong T-helper Type 1 Response?

A serious concern has been raised in the western world over the substantial increase in asthma and atopy prevalence over the last few decades. Changes in diagnostic procedures, genetic composition, or exposure to the conventional etiologic factors of asthma and atopy appear to be unable to explain most of this increase (1‐3). Several lines of evidence point to childhood infections providing significant protection from atopy (4‐7); the lack of microbial stimulation of sufficient intensity in early life may, paradoxically, affect the maturation of the immune system, leading to the predominance of a biased T-helper (Th)2 cell subtype in genetically susceptible individuals (8‐10). Intense childhood infections in western societies have become uncommon, and therefore the immune system may remain relatively unoccupied, a situation that may result in increased susceptibility to sensitization with otherwise harmless allergens in the environment (11). In contrast to certain natural infections, Calmette‐Guerin bacillus (BCG) vaccination has not had any effect on the subsequent development of asthma or atopy either in genetically predisposed (12) or in unselected Swedish (13) children. Probably only those infections that are able to mount a strong cell-mediated immune response and a long-living memory immunity may play a role here. Such infections are able to mobilize and activate tissue macrophages that migrate to regional lymph nodes and secrete cytokines that inhibit Th2 cell differentiation (10). On the basis of evidence obtained from humans (5‐7) and animal models (14, 15), we hypothesize that a vaccine that induces a strong Th1 immune response and a long-living memory immunity might in early life prevent the establishment of a biased Th2 cytokine milieu in the lungs of genetically predisposed children. This article briefly outlines the theoretical basis of the hypothesis and the possible role of mycobacterial vaccines in this immunomodulation. Background