Live attenuated malaria vaccine designed to protect through hepatic CD8+ T cell immunity

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

Research output: Contribution to journalArticlepeer-review

392 Scopus citations


Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in ≥80% of recipients. Pf sporozoites (Pf SPZ) 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-specific 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.

Original languageEnglish (US)
Pages (from-to)475-480
Number of pages6
Issue number6055
StatePublished - Oct 28 2011
Externally publishedYes

ASJC Scopus subject areas

  • General


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