141 ISSN 1750-743X 10.2217/1750-743X.1.1.141 © 2009 Future Medicine Ltd Immunotherapy (2009) 1(1), 141–156 Review Maternal immunization to modulate the development of allergic response and pathogen infections Impact of prenatal & postnatal allergen exposure on neonate sensitization The prevalence of atopic disease, such as asthma, atopic dermatitis, eczema and food allergies, has increased considerably in the last few decades [1,2] . Familiar history of atopy and frequent exposure to a given allergen in childhood are high-risk fac- tors for the development of allergic symptoms. Allergy development could have very precocious origins, most likely within the initial months of life [3,4] . The hypothesis that early events occur- ring during fetal development and/or in child- hood could determine allergic disease in adult- hood is sustained by clinical and epidemiological observations [5–7] . Cross-sectional and longitudi- nal studies indicate a stronger influence in relation to maternal atopy, a factor that might be related to genetic and/or environmental factors [7,8] . A cohort study has described that maternal, but not paternal, atopy has a significant impact on the elevation of cord blood IgE levels [9] . Elevation of IgE has been demonstrated to be a risk predic- tor for development of aeroallergen sensitization [10] and for the later development of childhood asthma [11] . Gene–environment interactions of CTLA-4 gene polymorphism [12] , and IL-13 and CD14 gene polymorphism with pet exposure [13] , have been demonstrated to affect antenatal IgE production and specific allergy sensitization. The predominance of a physiological pattern of maternal Th2 cytokines can strongly influ- ence atopy development during pregnancy in prone individuals. Fetal development occurs in a Th2 cytokine environment in order to provide conception survival, whereas IFN-γ is required for embryo implantation, but increased levels should be deleterious to the fetus [14–16] . Children of mothers sensitized with aeroaller- gens showed an early increase in Th2 cytokines and diminished IFN- γ secretions, suggesting that maternal cytokine and allergen sensitiza- tion can directly influence the profile of infant cytokine secretions that favor allergy develop- ment [17–19] . A murine model of allergic sensi- tization during pregnancy demonstrated that maternal ovalbumin (OVA)-specific Th2 cells exerted a critical role on the development of allergic response in early life [20] . Maternal transference of an allergen can sensi- tize the fetal immune system and promote immu- nity or tolerance to the transferred antigen. This implies that the fetus absorbs the macromolecules of the amniotic fluid by direct exposure through the skin, respiratory and GI tracts. The intestine is the principal route of fetus sensitization, since an allergen in the amniotic fluid can reach the gut-associated lymphoid tissue (GALT) where lymphoid structures, such as lymphoid follicles, Peyer’s patch and M cells, are structurally mature after week 19 of pregnancy [21]. Airborne allergens, such as Der p from the dust mite Dermatophagoides pteronyssinus, are detectable in maternal serum (21% of analyzed samples), amniotic liquid (56%) and full-term fetal serum, showing the transamniotic and placentary contributions of This article reviews recent experimental approaches of preventive strategies regarding allergy and infections by pathogens, particularly in early childhood, by targeting maternal immunomodulation. Basic research is essential to understand maternal vaccination as a strategy to control allergic disease and bacterial and viral infections; thus, providing support for future translational research. The environmental stimuli and host genetic factors, along with maternal influences in early life when immune systems are developing and during postnatal life, are essential for the decision between tolerance induction or allergen sensitization. Maternal immunomodulation strategies should serve as a challenge when attempting to halt the spread of allergy responses and viral infections, until the innate and adaptive arms of the immune system of the neonates are competent. KEYWORDS: allergy n breastfeeding n DNA vaccines n immunotherapy n infections n maternal antibodies n maternal immunomodulation n neonatal intervention n pregnancy Paula Ordonhez Rigato, Ana Elisa Fusaro, Jeferson Russo Victor & Maria Notomi Sato † † Author for correspondence: Laboratório de Dermatologia e Imunodeiciências – LIM56, Faculdade de Medicina da Universidade de São Paulo, Insituto de Medicina Tropical – Prédio II, Av Dr Enéas de Carvalho Aguiar, 500, 3º andar, 05403-05000, São Paulo, Brazil Tel.: +55 11 3061 7499 Fax: +55 11 3081 7190 marisato@usp.br For reprint orders, please contact: reprints@futuremedicine.com