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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Epstein, JE; Tewari, K; Lyke, KE; Sim, BKL; Billingsley, PF; Laurens, MB; Gunasekera, A; Chakravarty, S; James, ER; Sedegah, M; Richman, A; Velmurugan, S; Reyes, S; Li, M; Tucker, K; Ahumada, A; Ruben, AJ; Li, T; Stafford, R; Eappen, AG; Tamminga, C; Bennett, JW; Ockenhouse, CF; Murphy, JR; Komisar, J; Thomas, N; Loyevsky, M; Birkett, A; Plowe, CV; Loucq, C; Edelman, R; Richie, TL; Seder, RA; Hoffman, SL

Published Date

  • October 28, 2011

Published In

Volume / Issue

  • 334 / 6055

Start / End Page

  • 475 - 480

PubMed ID

  • 21903775

Pubmed Central ID

  • 21903775

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.1211548

Language

  • eng

Conference Location

  • United States