title: Protection against a malaria challenge by sporozoite inoculation.
abstract: BACKGROUND
  An effective vaccine for malaria is urgently needed. Naturally acquired immunity to malaria develops slowly, and induction of protection in humans can be achieved artificially by the inoculation of radiation-attenuated sporozoites by means of more than 1000 infective mosquito bites.
  
  
  METHODS
  We exposed 15 healthy volunteers--with 10 assigned to a vaccine group and 5 assigned to a control group--to bites of mosquitoes once a month for 3 months while they were receiving a prophylactic regimen of chloroquine. The vaccine group was exposed to mosquitoes that were infected with Plasmodium falciparum, and the control group was exposed to mosquitoes that were not infected with the malaria parasite. One month after the discontinuation of chloroquine, protection was assessed by homologous challenge with five mosquitoes infected with P. falciparum. We assessed humoral and cellular responses before vaccination and before the challenge to investigate correlates of protection.
  
  
  RESULTS
  All 10 subjects in the vaccine group were protected against a malaria challenge with the infected mosquitoes. In contrast, patent parasitemia (i.e., parasites found in the blood on microscopical examination) developed in all five control subjects. Adverse events were mainly reported by vaccinees after the first immunization and by control subjects after the challenge; no serious adverse events occurred. In this model, we identified the induction of parasite-specific pluripotent effector memory T cells producing interferon-gamma, tumor necrosis factor alpha, and interleukin-2 as a promising immunologic marker of protection.
  
  
  CONCLUSIONS
  Protection against a homologous malaria challenge can be induced by the inoculation of intact sporozoites. (ClinicalTrials.gov number, NCT00442377.)
authors.affiliation: Department of Medical Microbiology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Meta
authors.initials: M
authors.lastname: Roestenberg
authors.forename: Matthew
authors.initials: M
authors.lastname: McCall
authors.forename: Joost
authors.initials: J
authors.lastname: Hopman
authors.forename: Jorien
authors.initials: J
authors.lastname: Wiersma
authors.forename: Adrian J F
authors.initials: AJ
authors.lastname: Luty
authors.forename: Geert Jan
authors.initials: GJ
authors.lastname: van Gemert
authors.forename: Marga
authors.initials: M
authors.lastname: van de Vegte-Bolmer
authors.forename: Ben
authors.initials: B
authors.lastname: van Schaijk
authors.forename: Karina
authors.initials: K
authors.lastname: Teelen
authors.forename: Theo
authors.initials: T
authors.lastname: Arens
authors.forename: Lopke
authors.initials: L
authors.lastname: Spaarman
authors.forename: Quirijn
authors.initials: Q
authors.lastname: de Mast
authors.forename: Will
authors.initials: W
authors.lastname: Roeffen
authors.forename: Georges
authors.initials: G
authors.lastname: Snounou
authors.forename: Laurent
authors.initials: L
authors.lastname: Rénia
authors.forename: Andre
authors.initials: A
authors.lastname: van der Ven
authors.forename: Cornelus C
authors.initials: CC
authors.lastname: Hermsen
authors.forename: Robert
authors.initials: R
authors.lastname: Sauerwein
mesh_terms: D000328:Adult; D000818:Animals; D000852:Anopheles / Q000469:parasitology; D000913:Antibodies, Protozoan / Q000097:blood; D000962:Antimalarials / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001769:Blood / Q000469:parasitology; D002738:Chloroquine / Q000627:therapeutic use; D004311:Double-Blind Method; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D017780:Malaria Vaccines / Q000009:adverse effects / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D018512:Parasitemia; D010963:Plasmodium falciparum / Q000276:immunology / Q000302:isolation & purification; D034101:Sporozoites / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D000962:Antimalarials; D015415:Biomarkers; D007376:Interleukin-2; D017780:Malaria Vaccines; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D002738:Chloroquine