PREVENTION OF TH2-MEDIATED MURINE ALLERGIC AIRWAYS DISEASE BY SOLUBLE-ANTIGEN ADMINISTRATION IN THE NEONATE

It has been demonstrated recently that neonatal antigen administration in the mouse can lead to priming for Th2-mediated immune responses. T his observation has important implications for the development of vacc ination strategies in humans, particularly for individuals who may be predisposed to atopy or asthma. In this paper it is shown that althoug h i.p. administration of antigen (100 mu g) in adjuvant to the neonate does indeed prime for Th2-mediated disease in mice [allergic airways disease (AAD)], when the same relatively low dose of antigen is given in soluble form no priming occurs. Further, administration of a larger dose of soluble antigen (1 mg) actually prevents the ability to prime for a Th2 response subsequently and so prevents the induction of AAD. Protection from disease was associated with evidence of functional in activation of both Th1 and Th2 ovalbumin-specific T cells. In contrast , administration of a very low dose of antigen (10 mu g) primed for a Th2 response in a similar fashion to antigen in adjuvant. We suggest t hat the adjuvant lowers the ''effective'' dose of antigen administered in the neonate and thereby primes for Th2-type immune responses. Thes e findings demonstrate that neonatal antigen administration can inhibi t Th2-mediated diseases, such as AAD, but the dose of antigen may be c ritical to avoid predisposition to disease.