title: Immunization with genetically attenuated P. falciparum parasites induces long-lived antibodies that efficiently block hepatocyte invasion by sporozoites.
abstract: Whole-parasite malaria vaccines have shown promise in clinical trials. We recently reported the first human trial of a malaria vaccine based on Plasmodium falciparum genetically attenuated parasites (PfGAP). Herein we report for the first time that PfGAP induces prolonged functional humoral responses in humans. Six volunteers were exposed to 5 bites of PfGAP-infected mosquitoes followed by approximately 200 bites. Plasma collected from all volunteers 3 months after the last exposure efficiently inhibits invasion of hepatocytes by P. falciparum sporozoites. The level of inhibition observed is comparable to that attained using plasma collected after 4-5 intravenously administrations of high numbers of irradiated sporozoites, validating the potential of PfGAP malaria vaccines. Our data highlight the role of antibody responses in pre-erythrocytic stages of human malaria, and suggests that to be protective, malaria vaccines might need to elicit long-lasting functional antibodies in addition to cellular responses.
authors.affiliation: Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA, 98109, USA.
authors.forename: Olivia C
authors.initials: OC
authors.lastname: Finney
authors.affiliation: Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA, 98109, USA.
authors.forename: Gladys J
authors.initials: GJ
authors.lastname: Keitany
authors.affiliation: Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA, 98109, USA.
authors.forename: Hannah
authors.initials: H
authors.lastname: Smithers
authors.affiliation: Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA, 98109, USA.
authors.forename: Alexis
authors.initials: A
authors.lastname: Kaushansky
authors.affiliation: Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA, 98109, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kappe
authors.affiliation: Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA, 98109, USA. Electronic address: ruobing.wang@seattlebiomed.org.
authors.forename: Ruobing
authors.initials: R
authors.lastname: Wang
mesh_terms: D000913:Antibodies, Protozoan / Q000097:blood*; D002460:Cell Line; D022781:Hepatocytes / Q000469:parasitology*; D006801:Humans; D056724:Immunity, Humoral; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D010963:Plasmodium falciparum / Q000235:genetics; D034101:Sporozoites / Q000276:immunology; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D014613:Vaccines, Attenuated
keywords: ISI; Malaria; PfGAP; Vaccines; Whole-parasite immunization