title: Vaccine-induced monoclonal antibodies targeting circumsporozoite protein prevent Plasmodium falciparum infection.
abstract: Malaria, which is the result of Plasmodium falciparum infection, is a global health threat that resulted in 655,000 deaths and 216 million clinical cases in 2010 alone. Recent phase 3 trials with malaria vaccine candidate RTS,S/AS01 (RTS,S) in children has demonstrated modest efficacy against clinical and severe malaria. RTS,S targets the pre-erythrocytic phase of the disease and induces high antibody titers against the P. falciparum circumsporozoite protein (CSP) and a moderate CD4(+) T cell response. The individual contribution of these adaptive immune responses to protection from infection remains unknown. Here, we found that prophylactic administration of anti-CSP mAbs derived from an RTS,S-vaccinated recipient fully protected mice with humanized livers from i.v.- and mosquito bite–delivered P. falciparum sporozoite challenge. Titers of anti-CSP that conveyed full protection were within the range observed in human RTS,S vaccine recipients. Increasing anti-CSP titers resulted in a dose-dependent reduction of the liver parasite burden. These data indicate that RTS,S-induced antibodies are protective and provide sterilizing immunity against P. falciparum infection when reaching or exceeding a critical plasma concentration.
authors.forename: Lander
authors.initials: L
authors.lastname: Foquet
authors.forename: Cornelus C
authors.initials: CC
authors.lastname: Hermsen
authors.forename: Geert-Jan
authors.initials: GJ
authors.lastname: van Gemert
authors.forename: Eva
authors.initials: E
authors.lastname: Van Braeckel
authors.forename: Karin E
authors.initials: KE
authors.lastname: Weening
authors.forename: Robert
authors.initials: R
authors.lastname: Sauerwein
authors.forename: Philip
authors.initials: P
authors.lastname: Meuleman
authors.forename: Geert
authors.initials: G
authors.lastname: Leroux-Roels
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002986:Clinical Trials as Topic; D006801:Humans; D008099:Liver / Q000469:parasitology; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D051379:Mice; D016513:Mice, SCID; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D034101:Sporozoites / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C577001:RTS,S-AS01 vaccine; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan