Immunotherapy of Asthma: Prospects for a Vaccine?
Recent animal experiments using live bacteria, bacterial components, or DNA give rise to the hope that it may be possible to develop novel vaccines protecting atopic-prone humans from developing asthma in their lifetime. The basis of these vaccinations is to induce Th1 immune responses leading to the production of interferon-g (IFN-g), IL-12, and IL-18. The presence of these cytokines during Th cell development have been shown to inhibit the development of allergen-speci¢c Th2 cells both in vitro and in vivo (3,4). Two approaches may prove successful. First, it has been suggested that the neonatal immune response of non-atopics is biased toward Th2 responses, which subsequently shift toward Th1 responses during the ¢rst few years of life. Children who become atopic do not lose the tendency to develop Th2 responses, thus developing allergenspeci¢c Th2 cells after being exposed to inhaled allergens (this process is called the atopic march). The idea is to treat children at an early age with reagents that cause a shift from the residual neonatal Th2 response to a more Th1-biased immune status. This could be achieved by unspeci¢c immunizations inducing local or systemic Th1 immune responses. It is hoped that this would protect children from developing allergen-speci¢c Th2-type cells during the ¢rst months and years of life. A second approach is based on the hypothesis that non-atopic individuals are protected from the development of asthma because they have developed allergen-speci¢c Th1 responses. The secretion of IFN-g by Th1 cells during the encounter with allergen is su⁄cient to suppress allergen-speci¢c Th2 cell development and thus the development of asthma, without causing any major immunopathology usually associated with Th1 immune responses directed against, for example, viruses or bacteria. The proposed vaccination regimes are aimed at establishing allergen-speci¢c Th1 memory immune responses against certain allergens. This could be achieved by immunizing children with allergens in conjunction with adjuvants or DNA vaccines inducing strong Th1 responses. This chapter focuses on the possible future use of attenuated live or killed bacteria, CpG oligonucleotides, and plasmid DNA as vaccines (or vaccine adjuvants) protecting against asthma in humans. Alternative methods are also brie£y reviewed. Furthermore, possible side e¡ects of the proposed vaccination strategies will also be discussed.