Protective Efficacy of Plasmodium vivax Radiation-Attenuated Sporozoites in Colombian Volunteers: A Randomized Controlled Trial

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. methodology/principal findings: 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. conclusion: immunization with pvras was safe,immunogenic,and induced sterile immunity in 42% of the fy+ volunteers. moreover,fy- volunteers were refractory to pv malaria. trial registration: identifier: nct01082341. © 2016 public library of science. all rights reserved.