This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hassett, D. E.
Right arrow Articles by Whitton, J. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hassett, D. E.
Right arrow Articles by Whitton, J. L.

 Previous Article  |  Next Article 

J. Virol., 10 1997, 7881-7888, Vol 71, No. 10
Copyright © 1997, American Society for Microbiology

Neonatal DNA immunization with a plasmid encoding an internal viral protein is effective in the presence of maternal antibodies and protects against subsequent viral challenge

DE Hassett, J Zhang and JL Whitton
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA.

Conventional vaccines are remarkably effective in adults but are much less successful in the very young, who are less able to initiate a mature immune response and who may carry maternal antibodies which inactivate standard vaccines. We set out to determine whether DNA immunization might circumvent these problems. We have previously shown that intramuscular injection of plasmid DNA encoding the nucleoprotein (NP) gene of lymphocytic choriomeningitis virus (LCMV) is capable of inducing immune responses and protecting 50% of adult mice against lethal and sublethal challenge with LCMV. Here we demonstrate that mouse pups injected with the same plasmid hours or days after birth produce major histocompatibility complex-restricted, NP-specific cytotoxic T lymphocytes (CTL) that persist into adulthood; 48% of vaccinated pups responded to subsequent sublethal viral challenge by the accelerated production of anti-NP LCMV-specific CTL, indicating that these animals had been successfully immunized by the plasmid DNA. In addition, these mice showed a >95% reduction in splenic viral titers 4 days postinfection compared to control mice, demonstrating a more rapid control of infection in vivo. Furthermore, pups born of and suckled on LCMV-immune dams (and therefore containing passively acquired anti-LCMV antibodies at the time of DNA inoculation) responded to the DNA vaccine in a similar manner, showing that maternally derived anti-LCMV antibodies do not significantly inhibit the generation of protective immune responses following DNA vaccination. These findings suggest that, at least in this model system, DNA immunization circumvents many of the problems associated with neonatal immunization.


This article has been cited by other articles:

  • Plotkin, S. A. (2009). Vaccines: the Fourth Century. CVI 16: 1709-1719 [Abstract] [Full Text]  
  • Capozzo, A. V. E., Cuberos, L., Levine, M. M., Pasetti, M. F. (2004). Mucosally Delivered Salmonella Live Vector Vaccines Elicit Potent Immune Responses against a Foreign Antigen in Neonatal Mice Born to Naive and Immune Mothers. Infect. Immun. 72: 4637-4646 [Abstract] [Full Text]  
  • Stanisic, D. I., Martin, L. B., Gatton, M. L., Good, M. F. (2004). Inhibition of 19-kDa C-Terminal Region of Merozoite Surface Protein-1-Specific Antibody Responses in Neonatal Pups by Maternally Derived 19-kDa C-Terminal Region of Merozoite Surface Protein-1-Specific Antibodies but Not Whole Parasite-Specific Antibodies. J. Immunol. 172: 5570-5581 [Abstract] [Full Text]  
  • Feuer, R., Mena, I., Pagarigan, R. R., Harkins, S., Hassett, D. E., Whitton, J. L. (2003). Coxsackievirus B3 and the Neonatal CNS: The Roles of Stem Cells, Developing Neurons, and Apoptosis in Infection, Viral Dissemination, and Disease. Am. J. Pathol. 163: 1379-1393 [Abstract] [Full Text]  
  • Adkins, B., Bu, Y., Guevara, P. (2002). Murine Neonatal CD4+ Lymph Node Cells Are Highly Deficient in the Development of Antigen-Specific Th1 Function in Adoptive Adult Hosts. J. Immunol. 169: 4998-5004 [Abstract] [Full Text]  
  • Zhang, J., Silvestri, N., Whitton, J. L., Hassett, D. E. (2002). Neonates Mount Robust and Protective Adult-Like CD8+-T-Cell Responses to DNA Vaccines. J. Virol. 76: 11911-11919 [Abstract] [Full Text]  
  • Fennewald, S. M., Aronson, J. F., Zhang, L., Herzog, N. K. (2002). Alterations in NF-{kappa}B and RBP-J{kappa} by Arenavirus Infection of Macrophages In Vitro and In Vivo. J. Virol. 76: 1154-1162 [Abstract] [Full Text]  
  • Pertmer, T. M., Oran, A. E., Moser, J. M., Madorin, C. A., Robinson, H. L. (2000). DNA Vaccines for Influenza Virus: Differential Effects of Maternal Antibody on Immune Responses to Hemagglutinin and Nucleoprotein. J. Virol. 74: 7787-7793 [Abstract] [Full Text]  
  • Schlereth, B., Germann,, P.-G., ter Meulen, V., Niewiesk, S. (2000). DNA vaccination with both the haemagglutinin and fusion proteins but not the nucleocapsid protein protects against experimental measles virus infection. J. Gen. Virol. 81: 1321-1325 [Abstract] [Full Text]  
  • Hassett, D. E., Zhang, J., Slifka, M., Whitton, J. L. (2000). Immune Responses following Neonatal DNA Vaccination Are Long-Lived, Abundant, and Qualitatively Similar to Those Induced by Conventional Immunization. J. Virol. 74: 2620-2627 [Abstract] [Full Text]  
  • Lewis, P. J., van Drunen Littel-van den Hurk, S., Babiuk, L. A. (1999). Induction of immune responses to bovine herpesvirus type 1 gD in passively immune mice after immunization with a DNA-based vaccine. J. Gen. Virol. 80: 2829-2837 [Abstract] [Full Text]  
  • Millan, C. L. B., Weeratna, R., Krieg, A. M., Siegrist, C.-A., Davis, H. L. (1998). CpG DNA can induce strong Th1 humoral and cell-mediated immune responses against hepatitis B surface antigen in young mice. Proc. Natl. Acad. Sci. USA 95: 15553-15558 [Abstract] [Full Text]  
  • Rodriguez, F., An, L. L., Harkins, S., Zhang, J., Yokoyama, M., Widera, G., Fuller, J. T., Kincaid, C., Campbell, I. L., Whitton, J. L. (1998). DNA Immunization with Minigenes: Low Frequency of Memory Cytotoxic T Lymphocytes and Inefficient Antiviral Protection Are Rectified by Ubiquitination. J. Virol. 72: 5174-5181 [Abstract] [Full Text]  
  • Wang, Y., Xiang, Z., Pasquini, S., Ertl, H. C. J. (1998). Effect of Passive Immunization or Maternally Transferred Immunity on the Antibody Response to a Genetic Vaccine to Rabies Virus. J. Virol. 72: 1790-1796 [Abstract] [Full Text]