Immunological Responses of Neonates and Infants to DNA Vaccines
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 WordsRodent CD8+ T-cell responses malaria maternal antibodies DNA vaccination
- 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
- 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
- 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