Systems analysis of protective immune responses to RTS,S malaria vaccination in humans

We applied a systems biology approach to study immune responses in subjects receiving 3 consecutive immunizations with RTS,S/AS01 (RRR), or in those receiving 2 immunizations of RTS,S/AS01, following a primary immunization with adenoviral Ad35 (ARR) vector expressing circumsporozoite protein. The clinical trial (NCT01366534) was conducted at Walter Reed Army Institute of Research (WRAIR) Malaria Vaccine Branch. 46 healthy malaria-naïve volunteers, randomized to two study arms participated in this study testing the efficacy of RTS,S and AdVac® malaria vaccine candidates. Study arm 1 (hereafter referred to as ARR), comprised of 25 volunteers who received the AdVac® vaccine composed of Ad35 vector expressing full length CSP, as a primary immunization, followed by two doses of RTS,S/AS01 vaccine. The subjects in the second arm, consisting of 21 volunteers, received three doses of RTS,S/AS01 (RRR regimen). Participants in both study arms were vaccinated at 28-day intervals, and subjected to controlled malaria infection 21 days following the final immunization. Controlled human malaria infection (CHMI) challenge was administered through five bites from malaria-infected mosquitoes to mimic natural infection. Parasitemia was monitored for 28 days, and immunomonitoring continued for 159 days following challenge. The study also included 12 non-vaccinated subjects as infectivity controls. Please note that the non-vaccinated subjects were not profiled by microarray; this cohort served only as infectivity controls, to confirm that the infection protocol was effective.