title: Breadth of humoral response and antigenic targets of sporozoite-inhibitory antibodies associated with sterile protection induced by controlled human malaria infection.
abstract: The development of an effective malaria vaccine has remained elusive even until today. This is because of our incomplete understanding of the immune mechanisms that confer and/or correlate with protection. Human volunteers have been protected experimentally from a subsequent challenge by immunization with Plasmodium falciparum sporozoites under drug cover. Here, we demonstrate that sera from the protected individuals contain neutralizing antibodies against the pre-erythrocytic stage. To identify the antigen(s) recognized by these antibodies, a newly developed library of P. falciparum antigens was screened with the neutralizing sera. Antibodies from protected individuals recognized a broad antigenic repertoire of which three antigens, PfMAEBL, PfTRAP and PfSEA1 were recognized by most protected individuals. As a proof of principle, we demonstrated that anti-PfMAEBL antibodies block liver stage development in human hepatocytes. Thus, these antigens identified are promising targets for vaccine development against malaria.
authors.affiliation: Laboratory of Pathogen Immunobiology, Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.
authors.forename: Kaitian
authors.initials: K
authors.lastname: Peng
authors.affiliation: Laboratory of Pathogen Immunobiology, Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.
authors.forename: Yun Shan
authors.initials: YS
authors.lastname: Goh
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore.
authors.forename: Anthony
authors.initials: A
authors.lastname: Siau
authors.affiliation: Centre d'Immunologie et de Maladies Infectieuses (CIMI) - Paris, Institut National de la Santé et de la Recherche Médicale (Inserm) U1135 - Centre National de la Recherche Scientifique (CNRS) ERL 8255, F-75013, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, UPMC UMRS CR7, F-75005, Paris, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Franetich
authors.affiliation: Laboratory of Pathogen Immunobiology, Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.|Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Wan Ni
authors.initials: WN
authors.lastname: Chia
authors.affiliation: Laboratory of Pathogen Immunobiology, Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.
authors.forename: Alice Soh Meoy
authors.initials: AS
authors.lastname: Ong
authors.affiliation: Laboratory of Pathogen Immunobiology, Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.
authors.forename: Benoit
authors.initials: B
authors.lastname: Malleret
authors.affiliation: Laboratory of Pathogen Immunobiology, Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.
authors.forename: Ying Ying
authors.initials: YY
authors.lastname: Wu
authors.affiliation: Centre d'Immunologie et de Maladies Infectieuses (CIMI) - Paris, Institut National de la Santé et de la Recherche Médicale (Inserm) U1135 - Centre National de la Recherche Scientifique (CNRS) ERL 8255, F-75013, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, UPMC UMRS CR7, F-75005, Paris, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Snounou
authors.affiliation: Department of Medical Microbiology, Radboud University, Nijmegen Medical Center, Nijmegen, Netherlands.
authors.forename: Cornelus C
authors.initials: CC
authors.lastname: Hermsen
authors.affiliation: Department of Global Health, College of Public Health, University of South Florida, Tampa, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Adams
authors.affiliation: Centre d'Immunologie et de Maladies Infectieuses (CIMI) - Paris, Institut National de la Santé et de la Recherche Médicale (Inserm) U1135 - Centre National de la Recherche Scientifique (CNRS) ERL 8255, F-75013, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, UPMC UMRS CR7, F-75005, Paris, France.|AP HP, Centre Hospitalo-Universitaire Pitié-Salpêtrière, F-75013, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Mazier
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Preiser
authors.affiliation: Department of Medical Microbiology, Radboud University, Nijmegen Medical Center, Nijmegen, Netherlands.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
authors.affiliation: Laboratory of Pathogen Immunobiology, Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.
authors.forename: Anne-Charlotte
authors.initials: AC
authors.lastname: Grüner
authors.affiliation: Laboratory of Pathogen Immunobiology, Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.|Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Laurent
authors.initials: L
authors.lastname: Rénia
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis; D000913:Antibodies, Protozoan / Q000096:biosynthesis*; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D000962:Antimalarials / Q000627:therapeutic use; D002738:Chloroquine / Q000627:therapeutic use; D003429:Cross Reactions; D015870:Gene Expression; D022781:Hepatocytes / Q000187:drug effects / Q000276:immunology / Q000469:parasitology; D006801:Humans; D007106:Immune Sera / Q000737:chemistry; D056724:Immunity, Humoral; D017780:Malaria Vaccines / Q000008:administration & dosage; D016778:Malaria, Falciparum / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D019151:Peptide Library; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D034101:Sporozoites / Q000276:immunology; D014611:Vaccination
chemical_list: D057134:Antibodies, Neutralizing; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000962:Antimalarials; D007106:Immune Sera; C468522:MAEBL protein, Plasmodium falciparum; D017780:Malaria Vaccines; D019151:Peptide Library; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; C000588691:SEA-1 protein, Plasmodium falciparum; C069428:thrombospondin-related adhesive protein, protozoan; D002738:Chloroquine