title: Antibodies to PfSEA-1 block parasite egress from RBCs and protect against malaria infection.
abstract: Novel vaccines are urgently needed to reduce the burden of severe malaria. Using a differential whole-proteome screening method, we identified Plasmodium falciparum schizont egress antigen-1 (PfSEA-1), a 244-kilodalton parasite antigen expressed in schizont-infected red blood cells (RBCs). Antibodies to PfSEA-1 decreased parasite replication by arresting schizont rupture, and conditional disruption of PfSEA-1 resulted in a profound parasite replication defect. Vaccination of mice with recombinant Plasmodium berghei PbSEA-1 significantly reduced parasitemia and delayed mortality after lethal challenge with the Plasmodium berghei strain ANKA. Tanzanian children with antibodies to recombinant PfSEA-1A (rPfSEA-1A) did not experience severe malaria, and Kenyan adolescents and adults with antibodies to rPfSEA-1A had significantly lower parasite densities than individuals without these antibodies. By blocking schizont egress, PfSEA-1 may synergize with other vaccines targeting hepatocyte and RBC invasion.
authors.affiliation: Center for International Health Research, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
authors.forename: Dipak K
authors.initials: DK
authors.lastname: Raj
authors.affiliation: Center for International Health Research, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Nixon
authors.affiliation: Center for International Health Research, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
authors.forename: Christina E
authors.initials: CE
authors.lastname: Nixon
authors.affiliation: Division of Infectious Diseases, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Dvorin
authors.affiliation: Division of Infectious Diseases, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Christen G
authors.initials: CG
authors.lastname: DiPetrillo
authors.affiliation: Center for International Health Research, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
authors.forename: Sunthorn
authors.initials: S
authors.lastname: Pond-Tor
authors.affiliation: Center for International Health Research, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA. Department of Pediatrics, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
authors.forename: Hai-Wei
authors.initials: HW
authors.lastname: Wu
authors.affiliation: Department of Pathology and Laboratory Medicine, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI 02906, USA.
authors.forename: Grant
authors.initials: G
authors.lastname: Jolly
authors.affiliation: Center for International Health Research, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Pischel
authors.affiliation: Center for International Health Research, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
authors.forename: Ailin
authors.initials: A
authors.lastname: Lu
authors.affiliation: Center for International Health Research, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA. Department of Pediatrics, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Michelow
authors.affiliation: Center for International Health Research, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20892, USA.
authors.forename: Solomon
authors.initials: S
authors.lastname: Conteh
authors.affiliation: Center for International Health Research, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
authors.forename: Emily A
authors.initials: EA
authors.lastname: McDonald
authors.affiliation: Division of Infectious Diseases, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Absalon
authors.affiliation: Fred Hutchinson Cancer Research Center Program in Biostatistics and Biomathematics, Department of Biostatistics and Global Health, University of Washington, Seattle, WA 98109, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Holte
authors.affiliation: Center for International Health Research, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA. Department of Pediatrics, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
authors.forename: Jennifer F
authors.initials: JF
authors.lastname: Friedman
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20892, USA.
authors.forename: Michal
authors.initials: M
authors.lastname: Fried
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20892, USA.
authors.forename: Patrick E
authors.initials: PE
authors.lastname: Duffy
authors.affiliation: Center for International Health Research, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA. Department of Pathology and Laboratory Medicine, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI 02906, USA. jonathan_kurtis@brown.edu.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Kurtis
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology*; D000953:Antigens, Protozoan / Q000276:immunology*; D002648:Child; D004912:Erythrocytes / Q000469:parasitology*; D022781:Hepatocytes / Q000276:immunology / Q000469:parasitology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007630:Kenya; D008288:Malaria / Q000517:prevention & control; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D051379:Mice; D010962:Plasmodium berghei / Q000276:immunology; D010963:Plasmodium falciparum / Q000254:growth & development* / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D052939:Schizonts / Q000254:growth & development*; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C000588691:SEA-1 protein, Plasmodium falciparum