title: Pre-erythrocytic antibody profiles induced by controlled human malaria infections in healthy volunteers under chloroquine prophylaxis.
abstract: Complete sterile protection to Plasmodium falciparum (Pf) infection mediated by pre-erythrocytic immunity can be experimentally induced under chloroquine prophylaxis, through immunization with sporozoites from infected mosquitoes' bites (CPS protocol). To characterize the profile of CPS induced antibody (Ab) responses, we developed a proteome microarray containing 809 Pf antigens showing a distinct Ab profile with recognition of antigens expressed in pre-erythrocytic life-cycle stages. In contrast, plasma from naturally exposed semi-immune individuals from Kenya was skewed toward antibody reactivity against asexual blood stage antigens. CPS-immunized and semi-immune individuals generated antibodies against 192 and 202 Pf antigens, respectively, but only 60 antigens overlapped between the two groups. Although the number of reactive antigens varied between the CPS-immunized individuals, all volunteers reacted strongly against the pre-erythrocytic antigens circumsporozoite protein (CSP) and liver stage antigen 1 (LSA1). Well classified merozoite and erythrocytic antigens were strongly reactive in semi-immune individuals but lacking in the CPS immunized group. These data show that the antibody profile of CPS-immunized and semi-immune groups have quite distinct profiles reflecting their protective immunity; antibodies from CPS immunized individuals react strongly against pre-erythrocytic while semi-immune individuals mainly react against erythrocytic antigens.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of California, Irvine, CA 92697, USA.
authors.forename: Philip L
authors.initials: PL
authors.lastname: Felgner
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Meta
authors.initials: M
authors.lastname: Roestenberg
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of California, Irvine, CA 92697, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of California, Irvine, CA 92697, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Hung
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of California, Irvine, CA 92697, USA.
authors.forename: Aarti
authors.initials: A
authors.lastname: Jain
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of California, Irvine, CA 92697, USA.
authors.forename: Jozelyn
authors.initials: J
authors.lastname: Pablo
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of California, Irvine, CA 92697, USA.
authors.forename: Rie
authors.initials: R
authors.lastname: Nakajima-Sasaki
authors.affiliation: Antigen Discovery, Inc., Irvine, CA 92618, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Molina
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Karina
authors.initials: K
authors.lastname: Teelen
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Cornelus C
authors.initials: CC
authors.lastname: Hermsen
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Robert
authors.initials: R
authors.lastname: Sauerwein
mesh_terms: D000906:Antibodies / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology*; D000962:Antimalarials / Q000627:therapeutic use; D002738:Chloroquine / Q000627:therapeutic use; D004912:Erythrocytes / Q000469:parasitology; D064368:Healthy Volunteers; D006801:Humans; D007630:Kenya; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control; D010963:Plasmodium falciparum / Q000276:immunology*; D040081:Protein Array Analysis; D015800:Protozoan Proteins / Q000276:immunology*; D034101:Sporozoites / Q000276:immunology*
chemical_list: D000906:Antibodies; D000953:Antigens, Protozoan; D000962:Antimalarials; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan; C067302:liver stage-specific antigen, Plasmodium; D002738:Chloroquine