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1. Live Attenuated Malaria Vaccine Designed to Protect Through Hepatic CD8⁺ T Cell Immunity

Author

Epstein, J. E., Tewari, K., Lyke, K. E., Sim, B. K. L., Billingsley, P. F., Laurens, M. B., Gunasekera, A., Chakravarty, S., James, E. R., Sedegah, M., Richman, A., Velmurugan, S., Reyes, S., Li, M., Tucker, K., Ahumada, A., Ruben, A. J., Li, T., Stafford, R., Eappen, A. G., Tamminga, C., Bennett, J. W., Ockenhouse, C. F., Murphy, J. R., Komisar, J., Thomas, N., Loyevsky, M., Birkett, A., Plowe, C. V., Loucq, C., Edelman, R., Richie, T. L., Seder, R. A., and Hoffman, S. L.

Published
2011

2. Live Attenuated Malaria Vaccine Designed to Protect Through Hepatic CD8+ T Cell Immunity.

Author

Epstein, J. E., Tewari, K., Lyke, K. E., Sim, B. K. L., Billingsley, P. F., Laurens, M. B., Gunasekera, A., Chakravarty, S., James, E. R., Sedegah, M., Richman, A., Velmurugan, S., Reyes, S., Li, M., Tucker, K., Ahumada, A., Ruben, A. J., Li, T., Stafford, R., and Eappen, A. G.

Subjects
*IMMUNOLOGY, *MALARIA vaccines, *PLASMODIUM falciparum, *DRUG delivery systems, *INTRAVENOUS injections, *MALARIA prevention, *MOSQUITO vectors, *ANIMAL models in research, *HUMAN experimentation
Abstract

Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in ≥80% of recipients. Pf sporozoites (PfSPZ) administered by mosquito bites are the only immunogens shown to induce such protection in humans. Such protection is thought to be mediated by CD8+ T cells in the liver that secrete interferon-γ (IFN-γ). We report that purified irradiated PfSPZ administered to 80 volunteers by needle inoculation in the skin was safe, but suboptimally immunogenic and protective. Animal studies demonstrated that intravenous immunization was critical for inducing a high frequency of PfSPZ-speciflc CD8+ IFN-γ-producing T cells in the liver (nonhuman primates, mice) and conferring protection (mice). Our results suggest that intravenous administration of this vaccine will lead to the prevention of infection with Pf malaria. [ABSTRACT FROM AUTHOR]

Published
2011
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