Science        
28 October 2011 vol 334, issue 6055, pages 421-552
http://www.sciencemag.org/current.dtl

Research Articles
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. Eappen, C. 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, and S. L. Hoffman
Science 28 October 2011: 475-480.
Published online 8 September 2011 [DOI:10.1126/science.1211548]
The efficacy of a sporozoite-based malaria vaccine is tested in humans, nonhuman primates, and mice.

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-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.