Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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 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.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it


Prices may be subject to local taxes which are calculated during checkout

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.


  1. Wright, P.F. & Wright, P.F. Infectious diseases in early life in industrialized countries. Vaccine 16, 1355–1359 (1998).

    Article  CAS  Google Scholar 

  2. Mulholland, K. Serious infections in young infants in developing countries. Vaccine 16, 1360–1362 (1998).

    Article  CAS  Google Scholar 

  3. Hein, W.R. Sheep as experimental animals for immunological research. The Immunologist 3, 12–18 (1995).

    Google Scholar 

  4. Auphan, N., DiDonato, J.A., Rosette, C., Helmberg, A. & Karin, M. Immunosuppression by glucocorticoids; inhibition of NF-β activity through induction of I β synthesis. Science 270, 286–290 (1995).

    Article  CAS  Google Scholar 

  5. Van Drunen Littel-van den Hurk, S. et al. Immunization of neonates with DNA encoding a bovine herpesvirus glycoprotein is effective in the presence of maternal antibodies. Viral Immunol. 12, 67–77 (1999).

    Article  CAS  Google Scholar 

  6. Donelly, J.J., Ulmer, J.B., Shiver, J.W. & Liu, M.A. DNA vaccines. Annu. Rev. Immunol. 15, 617–648 (1997).

    Article  Google Scholar 

  7. McCluskie, M.J. & Davis, H.L. Novel strategies using DNA for the induction of mucosal immunity. Crit. Rev. Immunol. 19, 303–329 (1999).

    CAS  PubMed  Google Scholar 

  8. Baba, T.W. et al. Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian–human immunodeficiency virus infection. Nature Med. 6, 200–206 (2000).

    Article  CAS  Google Scholar 

  9. Mascola, J.R. et al. Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus by passive fusion of neutralizing antibodies. Nature Med. 6, 207–210 (2000).

    CAS  Google Scholar 

  10. Watts, A.M., Stanley, J.R., Shearer, M.H., Hefty, P.S. & Kennedy, R.C. Fetal immunization of baboons induce a fetal-specific antibody response. Nature Med. 5, 427–430 (1999).

    Article  CAS  Google Scholar 

  11. Gaensler, K.M. et al. Fetal gene transfer by transuterine injection of cationic liposome-DNA complexes. Nature Biotechnol. 17, 1188–1192 (1999).

    Article  CAS  Google Scholar 

  12. Ridge, J.P., Fuchs, E.J. & Matzinger, P. Neonatal tolerance revisited: turning on newborn T cells with dendritic cells. Science 271, 1723–1726 (1996).

    Article  CAS  Google Scholar 

  13. Sarzotti, M., Robbins, D.S. & Hoffman P.M. Induction of protective CTL responses in newborn mice by a murine Retrovirus. Science 271, 1726–1728 (1996).

    Article  CAS  Google Scholar 

  14. Forsthuber, T., Yip, H.C. & Lehmann P.V. Induction of Th1 and Th2 Immunity in neonatal mice. Science 271, 1728–1730 (1996).

    Article  CAS  Google Scholar 

  15. Butts, C., Zubkoff, I., Robbins, D.S., Cao, S. & Sarzotti M. DNA immunization of infants: potential and limitations. Vaccine 16, 1444–1449 (1998).

    Article  CAS  Google Scholar 

  16. Mor, G., et al. Induction of neonatal tolerance by plasmid DNA vaccination of mice. J. Clin. Invest. 98, 2700–2705 (1996).

    Article  CAS  Google Scholar 

  17. Ichino, M. et al. Factors associated with the development of neonatal tolerance after the administration of a plasmid DNA vaccine. J. Immunol. 162, 3814–3818 (1999).

    CAS  PubMed  Google Scholar 

  18. Isshii, K.J., Weiss, W. & Klinman D.M. Prevention of neonatal tolerance by a plasmid encoding granulocyte-macrophage colony stimulating factor. Vaccine 18, 703–710 (2000).

    Article  Google Scholar 

  19. Iwamoto, H.S., Trapnell, B.C., McConnell, C.J., Daugherty, C. & Whitsett, J.A. Pulmonary inflammation associated with repeated, prenatal exposure to an E1, E3-deleted adenoviral vector in sheep. Gene Ther. 6, 98–106 (1999).

    Article  CAS  Google Scholar 

  20. Braun, R.P., Babiuk, L.A. & van Drunen Littel-van den Hurk, S. Enhanced immune response to an intradermally derived DNA vaccine expressing a secreted form of BHV-1 gD. Vaccine Res. 6, 151–164 (1997).

    CAS  Google Scholar 

Download references


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.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Philip J. Griebel.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing