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BACKGROUND: The need for a highly efficacious vaccine against Plasmodium falciparum remains pressing. In this controlled human malaria infection (CHMI) study, we assessed the safety, efficacy and immunogenicity of a schedule combining 2 distinct vaccine types in a staggered immunization regimen: one inducing high-titer antibodies to circumsporozoite protein (RTS,S/AS01B) and the other inducing potent T-cell responses to thrombospondin-related adhesion protein (TRAP) by using a viral vector. METHOD: Thirty-seven healthy malaria-naive adults were vaccinated with either a chimpanzee adenovirus 63 and modified vaccinia virus Ankara-vectored vaccine expressing a multiepitope string fused to TRAP and 3 doses of RTS,S/AS01B (group 1; n = 20) or 3 doses of RTS,S/AS01B alone (group 2; n = 17). CHMI was delivered by mosquito bites to 33 vaccinated subjects at week 12 after the first vaccination and to 6 unvaccinated controls. RESULTS: No suspected unexpected serious adverse reactions or severe adverse events related to vaccination were reported. Protective vaccine efficacy was observed in 14 of 17 subjects (82.4%) in group 1 and 12 of 16 subjects (75%) in group 2. All control subjects received a diagnosis of blood-stage malaria parasite infection. Both vaccination regimens were immunogenic. Fourteen protected subjects underwent repeat CHMI 6 months after initial CHMI; 7 of 8 (87.5%) in group 1 and 5 of 6 (83.3%) in group 2 remained protected. CONCLUSIONS: The high level of sterile efficacy observed in this trial is encouraging for further evaluation of combination approaches using these vaccine types. CLINICAL TRIALS REGISTRATION: NCT01883609.

Original publication




Journal article


J infect dis

Publication Date





772 - 781


ChAd63, ME-TRAP, P. falciparum, RTS,S, malaria, vaccine, Adenoviridae, Adolescent, Adult, Animals, Drug Carriers, Drug-Related Side Effects and Adverse Reactions, Female, Healthy Volunteers, Humans, Immunization Schedule, Malaria Vaccines, Malaria, Falciparum, Male, Middle Aged, Protozoan Proteins, Treatment Outcome, Vaccines, Combined, Vaccines, Synthetic, Vaccinia virus, Young Adult