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Fetal immunization by a DNA vaccine delivered into the oral cavity

Abstract

Infectious diseases are the main cause of neonatal morbidity and mortality in humans. The World Health Organization estimated that in 1995 approximately 8 million infants died within the first year of life from infectious diseases, including 5 million during the first week of life. Some of the salient pathogens involved include herpes simplex virus, human immunodeficiency virus, hepatitis B virus, human cytomegalovirus, group B streptococcus, hemophilus and chlamydia1,2. Infection with these pathogens usually occurs at the end of pregnancy, during birth or by breastfeeding. To reduce the risk of disease transmission, caesarian sections, prophylactic treatment with antibiotics or maternal antiviral therapy during the last trimester are used where available, together with improved neonatal care. None of these approaches, however, completely eliminates the risk of neonatal infection. Therefore, active or passive immunization of the fetus might represent an effective approach to reduce the high risk of neonatal diseases. Here, we demonstrate that a single immunization with a DNA vaccine delivered into the amniotic 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.

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Figure 1: Lymphoproliferative responses of fetal peripheral blood mononuclear cells and cells from the medial retropharyngeal lymph node.
Figure 2: Detection of gD-specific antibody-secreting cells in various lymph nodes.

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Acknowledgements

We thank D. Wilson, B. Carroll, C. Olson, J. Mamer, T. Bruneau and B. Evans for their help with housing the animals and with surgery; D. Dixon (Department of Animal and Poultry Science, University of Saskatchewan, Canada) for establishing a breeding program and providing pregnant ewes; and L. Polley for critically reviewing the manuscript. V.G. is funded by the Deutsche Forschungsgemeinschaft (DFG, Ge 1039/1-2). Research funding was provided by the Medical Research Council of Canada and Alberta Agriculture Research Institute. This article is published with permission of the Director of Veterinary Infectious Disease Organization as article number 278.

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Correspondence to Philip J. Griebel.

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Gerdts, V., Babiuk, L., van Drunen Littel-van den Hurk, S. et al. Fetal immunization by a DNA vaccine delivered into the oral cavity. Nat Med 6, 929–932 (2000). https://doi.org/10.1038/78699

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