title: Protective Efficacy of Plasmodium vivax Radiation-Attenuated Sporozoites in Colombian Volunteers: A Randomized Controlled Trial.
abstract: BACKGROUND
  Immunizing human volunteers by mosquito bite with radiation-attenuated Plasmodium falciparum sporozoites (RAS) results in high-level protection against infection. Only two volunteers have been similarly immunized with P. vivax (Pv) RAS, and both were protected. A phase 2 controlled clinical trial was conducted to assess the safety and protective efficacy of PvRAS immunization.
  
  
  RESULTS
  A randomized, single-blinded trial was conducted. Duffy positive (Fy+; Pv susceptible) individuals were enrolled: 14 received bites from irradiated (150 ± 10 cGy) Pv-infected Anopheles mosquitoes (RAS) and 7 from non-irradiated non-infected mosquitoes (Ctl). An additional group of seven Fy- (Pv refractory) volunteers was immunized with bites from non-irradiated Pv-infected mosquitoes. A total of seven immunizations were carried out at mean intervals of nine weeks. Eight weeks after last immunization, a controlled human malaria infection (CHMI) with non-irradiated Pv-infected mosquitoes was performed. Nineteen volunteers completed seven immunizations (12 RAS, 2 Ctl, and 5 Fy-) and received a CHMI. Five of 12 (42%) RAS volunteers were protected (receiving a median of 434 infective bites) compared with 0/2 Ctl. None of the Fy- volunteers developed infection by the seventh immunization or after CHMI. All non-protected volunteers developed symptoms 8-13 days after CHMI with a mean pre-patent period of 12.8 days. No serious adverse events related to the immunizations were observed. Specific IgG1 anti-PvCS response was associated with protection.
  
  
  CONCLUSIONS
  Immunization with PvRAS was safe, immunogenic, and induced sterile immunity in 42% of the Fy+ volunteers. Moreover, Fy- volunteers were refractory to Pv malaria.
  
  
  BACKGROUND
  Identifier: NCT01082341.
authors.affiliation: Malaria Vaccine and Drug Development Center (MVDC), Cali, Colombia.|Faculty of Health, Universidad del Valle, Cali, Colombia.
authors.forename: Myriam
authors.initials: M
authors.lastname: Arévalo-Herrera
authors.affiliation: Malaria Vaccine and Drug Development Center (MVDC), Cali, Colombia.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Vásquez-Jiménez
authors.affiliation: Malaria Vaccine and Drug Development Center (MVDC), Cali, Colombia.
authors.forename: Mary
authors.initials: M
authors.lastname: Lopez-Perez
authors.affiliation: Malaria Vaccine and Drug Development Center (MVDC), Cali, Colombia.
authors.forename: Andrés F
authors.initials: AF
authors.lastname: Vallejo
authors.affiliation: Malaria Vaccine and Drug Development Center (MVDC), Cali, Colombia.
authors.forename: Andrés B
authors.initials: AB
authors.lastname: Amado-Garavito
authors.affiliation: Malaria Vaccine and Drug Development Center (MVDC), Cali, Colombia.
authors.forename: Nora
authors.initials: N
authors.lastname: Céspedes
authors.affiliation: Malaria Vaccine and Drug Development Center (MVDC), Cali, Colombia.
authors.forename: Angélica
authors.initials: A
authors.lastname: Castellanos
authors.affiliation: Malaria Vaccine and Drug Development Center (MVDC), Cali, Colombia.
authors.forename: Karen
authors.initials: K
authors.lastname: Molina
authors.affiliation: Asoclinic Inmunología LTDA, Cali, Colombia.
authors.forename: Johanna
authors.initials: J
authors.lastname: Trejos
authors.affiliation: Centro Médico Imbanaco, Cali, Colombia.
authors.forename: José
authors.initials: J
authors.lastname: Oñate
authors.affiliation: Naval Medical Research Center, Malaria Department, Silver Spring, Maryland, United States of America.
authors.forename: Judith E
authors.initials: JE
authors.lastname: Epstein
authors.affiliation: Sanaria Inc, Rockville, Maryland, United States of America.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Richie
authors.affiliation: Malaria Vaccine and Drug Development Center (MVDC), Cali, Colombia.|Caucaseco Scientific Research Center, Cali, Colombia.
authors.forename: Sócrates
authors.initials: S
authors.lastname: Herrera
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000852:Anopheles / Q000469:parasitology*; D000913:Antibodies, Protozoan / Q000097:blood; D003105:Colombia; D004375:Duffy Blood-Group System; D005260:Female; D006801:Humans; D007114:Immunization / Q000009:adverse effects / Q000379:methods*; D007074:Immunoglobulin G / Q000097:blood; D007299:Insect Bites and Stings; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016780:Malaria, Vivax / Q000208:ethnology / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D010966:Plasmodium vivax / Q000276:immunology* / Q000502:physiology / Q000528:radiation effects; D016037:Single-Blind Method; D034101:Sporozoites / Q000528:radiation effects; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014838:Volunteers; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D004375:Duffy Blood-Group System; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D014613:Vaccines, Attenuated