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DNA Vaccines pp 239-251 | Cite as

Immunological Responses of Neonates and Infants to DNA Vaccines

  • Martha Sedegah
  • Stephen L. Hoffman
Part of the Methods in Molecular Medicine™ book series (MIMM, volume 127)

Abstract

In some parts of sub-Saharan Africa, it is believed that most of the deaths attributed to malaria occur in infants. For this and other logistical reasons, if a malaria vaccine is developed and licensed, it will have to be administered to neonates or young infants, when they have maternally acquired antibodies against malaria parasite proteins. Pre-erythrocytic malaria vaccines in development rely on CD8+ T cells as immune effectors, yet some studies indicate that neonates do not mount optimal CD8+ T-cell responses. We report that BALB/c mice first immunized as neonates (7 d) with a Plasmodium yoelii circumsporozoite protein (PyCSP) DNA vaccine mixed with a plasmid expressing murine granulocyte macrophage-colony stimulating factor (DG) and boosted at 28 d with pox virus expressing PyCSP were protected (93%) as well as mice immunized entirely as adults (70%). Like adults, protection was dependent on CD8+ T cells and accompanied by excellent anti-PyCSP interferon-γ and cytotoxic T-lymphocyte responses. Mice born of immune mothers (previously exposed to P. yoelii parasites or immunized with the same vaccine given to the neonates) were also protected and had excellent T-cell responses. These data support assessment of this immunization strategy in neonates/young infants in areas where malaria exacts the greatest toll.

Key Words

Rodent CD8+ T-cell responses malaria maternal antibodies DNA vaccination 

References

  1. 1.
    Hoffman, S. L. (2004) Save the children. Nature 430, 940–941.CrossRefPubMedGoogle Scholar
  2. 2.
    Binka, F. N., Morris, S. S., Ross, D. A., Arthur, P., and Aryeetey, M. E. (1994) Patterns of malaria morbidity and mortality in children in northern Ghana. Trans. R. Soc. Trop. Med. Hyg. 88, 381–385.CrossRefPubMedGoogle Scholar
  3. 3.
    Albrecht, P., Ennis, F. A., and Saltzman, E. J. (1977) Persistence of maternal antibody in infants beyond 12 months: mechanisms of measles vaccine failure. J. Pediatr. 91, 715–718.CrossRefPubMedGoogle Scholar
  4. 4.
    Murphy, B. R., Olmsted, R. A., Collins, P. L., Chanock, R. M., and Prince, G. A. (1988) Passive transfer of respiratory syncytial virus (RSV) antiserum suppresses the immune response to the RSV fusion (F) and large (G) glycoproteins expressed by recombinant vaccinia viruses. J. Virol. 62, 3907–3910.PubMedGoogle Scholar
  5. 5.
    Van Maanen, C., Bruin, G., and deBoer-Liutzje, E. (1992) Interference of maternal antibodies with the immune response of foals after vaccination against equine influenza. Vet. Q. 14, 13–17.PubMedGoogle Scholar
  6. 6.
    Siegrist, C. A., Barrios, C., Martinez, X., et al. (1998) Influence of maternal antibodies on vaccine responses: inhibition of antibody but not T cell responses allows successful early prime-boost strategies in mice. Eur. J. Immunol. 28, 4138–4148.CrossRefPubMedGoogle Scholar
  7. 7.
    Mor, G., Yamshchiov, G., Sedegah, M., et al. (1996) Induction of neonatal tolerance by plasmid DNA vaccination of mice. J. Clin. Invest. 98, 2700–2705.CrossRefPubMedGoogle Scholar
  8. 8.
    Sedegah, M., Hedstrom, R., Hobart, P., and Hoffman, S. L. (1994) Protection against malaria by immunization with plasmid DNA encoding circumsporozoite protein. Proc. Natl. Acad. Sci. USA 91, 9866–9870.CrossRefPubMedGoogle Scholar
  9. 9.
    Wang, R., Doolan, D. L., Le, T. P., et al. (1998) Induction of antigen-specific cytotoxic T lymphocytes in humans by a malaria DNA vaccine. Science 282, 476–479.CrossRefPubMedGoogle Scholar
  10. 10.
    Le, T. P., Coonan, K. M., Hedstrom, R. C., et al. (2000) Safety, tolerability and humoral immune responses after intramuscular administration of malaria DNA vaccine to healthy adult volunteers. Vaccine 18, 1893–1901.CrossRefPubMedGoogle Scholar
  11. 11.
    Siegrist, C. A. (2001) Neonatal and early life vaccinology. Vaccine 19, 3331–3346.CrossRefPubMedGoogle Scholar
  12. 12.
    Manickan, E., Yu, Z., and Rouse, B. T. (1997) DNA Immunization of neonates induces immunity despite the presence of maternal antibody. J. Clin. Invest. 100, 2371–2375.CrossRefPubMedGoogle Scholar
  13. 13.
    Brazolot-Millan C. L. and Davis, H. L. (2000) DNA-based immunization of neonatal mice. In: DNA Vaccines: Methods and Protocols, Methods in Molocular Medicine, vol 29, (Lowrie, D. B., and Whalen, R. G., eds.), Humana Press Inc., Totowa, NJ, pp. 95–98.Google Scholar
  14. 14.
    Sedegah, M., Weiss, W., Sacci, J. B., et al. (2000) Improving protective immunity induced by DNA-based immunization: priming with antigen and GM-CSF encoding plasmid DNA and boosting with antigen expressing recombinant poxvirus. J. Immunol. 164, 5905–5912.PubMedGoogle Scholar
  15. 15.
    Sedegah, M., Jones, T. R., Kaur, M., et al. (1998) Boosting with recombinant vaccinia increases immunogenecity and protective efficacy of malaria. Proc. Natl. Acad. Sci. USA 95, 7648–7653.CrossRefPubMedGoogle Scholar
  16. 16.
    Weiss, W. R., Ishii, K. J., Hedstrom, R. C., et al. (1998) A plasmid encoding murine granulocyte-macrophage colony-stimulating factor increases protection conferred by a malaria DNA vaccine. J. Immunol. 161, 2325–2332.PubMedGoogle Scholar
  17. 17.
    Sedegah, M., Belmonte, M., Epstein, J. E., et al. (2003) Successful induction of CD8 T cell-dependent protection against malaria by sequential immunization with DNA and recombinant poxvirus of neonatal mice born to immune mothers. J. Immunology 171, 3148–3153.Google Scholar

Copyright information

© Humana Press Inc. 2006

Authors and Affiliations

  • Martha Sedegah
    • 1
  • Stephen L. Hoffman
    • 2
  1. 1.Malaria ProgramNaval Medical Research CenterSilver Spring
  2. 2.Samaria Inc.Rockville

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