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

• DOI: 10.1126/science.1211548
• Publication Date: 2011-09-09T13:30:14Z
• Authors: 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; S. L. Hoffman
• Keywords: Cell mediated immunity; Attenuated vaccine

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 induce such protection humans. Such thought be mediated CD8(+) T cells liver secrete interferon-γ (IFN-γ). We report purified irradiated PfSPZ 80 volunteers needle inoculation skin was safe, but suboptimally immunogenic and protective. Animal studies demonstrated intravenous immunization critical for inducing high frequency PfSPZ-specific CD8(+), IFN-γ-producing (nonhuman primates, mice) conferring (mice). results suggest administration this will lead prevention infection with malaria.