title: Live attenuated malaria vaccine designed to protect through hepatic CD8⁺ T cell immunity.
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.
authors: U.S. Military Malaria Vaccine Program, Naval Medical Research Center, Silver Spring, MD 20910, USA.
authors: J E
authors: JE
authors: Epstein
authors: K
authors: K
authors: Tewari
authors: K E
authors: KE
authors: Lyke
authors: B K L
authors: BK
authors: Sim
authors: P F
authors: PF
authors: Billingsley
authors: M B
authors: MB
authors: Laurens
authors: A
authors: A
authors: Gunasekera
authors: S
authors: S
authors: Chakravarty
authors: E R
authors: ER
authors: James
authors: M
authors: M
authors: Sedegah
authors: A
authors: A
authors: Richman
authors: S
authors: S
authors: Velmurugan
authors: S
authors: S
authors: Reyes
authors: M
authors: M
authors: Li
authors: K
authors: K
authors: Tucker
authors: A
authors: A
authors: Ahumada
authors: A J
authors: AJ
authors: Ruben
authors: T
authors: T
authors: Li
authors: R
authors: R
authors: Stafford
authors: A G
authors: AG
authors: Eappen
authors: C
authors: C
authors: Tamminga
authors: J W
authors: JW
authors: Bennett
authors: C F
authors: CF
authors: Ockenhouse
authors: J R
authors: JR
authors: Murphy
authors: J
authors: J
authors: Komisar
authors: N
authors: N
authors: Thomas
authors: M
authors: M
authors: Loyevsky
authors: A
authors: A
authors: Birkett
authors: C V
authors: CV
authors: Plowe
authors: C
authors: C
authors: Loucq
authors: R
authors: R
authors: Edelman
authors: T L
authors: TL
authors: Richie
authors: R A
authors: RA
authors: Seder
authors: S L
authors: SL
authors: Hoffman
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008099:Liver / Q000276:immunology*; D008253:Macaca mulatta; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D051379:Mice; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000276:immunology*; D011817:Rabbits; D034101:Sporozoites / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D014613:Vaccines, Attenuated; D007371:Interferon-gamma