Fetal immunization by a DNA vaccine delivered into the oral cavity

Infectious diseases are the main cause of neonatal morbidity and mortality in humans. The World Health Organization estimated that in 1995 approximate ly 8 million infants died within the first year of life from infectious dis eases, including 5 million during the first week of life. Some of the salie nt pathogens involved include herpes simplex virus, human immunodeficiency virus, hepatitis B virus, human cytomegalovirus, group B streptococcus, hem ophilus and chlamydia(1,2). Infection with these pathogens usually occurs a t the end of pregnancy, during birth or by breastfeeding. To reduce the ris k of disease transmission, caesarian sections, prophylactic treatment with antibiotics or maternal antiviral therapy during the last trimester are use d where available, together with improved neonatal care. None of these appr oaches, however, completely eliminates the risk of neonatal infection. Ther efore, active or passive immunization of the fetus might represent an effec tive approach to reduce the high risk of neonatal diseases. Here, we demons trate that a single immunization with a DNA vaccine delivered into the amni otic fluid in the oral cavity induces high serum antibody titers and a cell -mediated immune response, combined with induction of local immunity in the oral cavities of fetal lambs.