Preventive vaccination against allergy: the effect in offspring of maternal allergen exposure and immune response

Allergy-related diseases affect in the order of 30% of the population, and represent one of the most common health problems caused by environmental factors in interplay with genetically and epigenetically determined susceptibility of the individual. The causes for allergy are largely unknown, and no effective prevention for this disease of the immune system is known. We have in a mouse model found preventive vaccination of the mother with allergen highly effective in reducing the allergic immune respons e in the offspring (Melkild et al., 2002). We ask for funding to develop this concept further in mouse and rat models, with the ultimate aim of use in humans. The overall goal of the project is to determine the effect on allergy in the offspring from mat ernal exposure and immune response to allergen before and during pregnancy and lactation. Apart from vaccination, the findings will have relevance for the understanding of the role of maternal allergen exposure in general (via food, skin and inhalation) f or allergy in the offspring. The project has three major goals: i) a better characterization of the existing model, which is based on subcutaneous immunization of the pregnant mother with the allergen ovalbumin. The model will be characterized in terms of optimal conditions for vaccination, and duration and optimal requirements for protection in the offspring ii) extending the model with alternative routes of vaccination, specifically epicutaneous, intranasal and peroral vaccination, and with food and respiratory allergens, and in an other species,the rat iii) better understanding of immunological and epigenetic mechanisms. In addition to the importance of the research goals, the project will serve as a post-doc-project with international training in laboratories in The Netherlands and England. However, most important, the project will pave a hitherto virtually unexplored road of harnessing epigenetic mechanisms to achieve allergy prevention.