The RTS,S malaria vaccine.
RTS,S is the most advanced candidate vaccine against human malaria. During its remarkable journey from conception and design in the early 1980s to the multicenter Phase 3 trial currently underway across sub-Saharan Africa, RTS,S has overcome tremendous challenges and disproved established vaccine paradigms. In the last several years, Phase 2 studies conducted in infants and children in endemic areas have established the efficacy of RTS,S for reducing morbidity due to clinical malaria. If the results are realized in the Phase 3 trial, the chances for licensure in the near future appear high. Such progress is all the more remarkable given our lack of clear understanding regarding how the vaccine activates the human immune system, the immune correlates of protection or the mechanism whereby a vaccine targeting sporozoites and liver stage parasites can reduce the clinical disease associated with parasitemia. These unanswered questions pose important challenges to be addressed in the quest to understand the protection afforded by RTS,S and to build a more efficacious second generation vaccine against malaria. This review will focus on current knowledge about the protective efficacy of RTS,S and what we have learned regarding its impact on the human immune system.
Casares
Sofia
S
US Military Malaria Vaccine Program, Naval Medical Research Center/Walter Reed Army Institute of Research, Silver Spring, MD, USA. sofia.casares@med.navy.mil
Brumeanu
Teodor-Doru
TD
Richie
Thomas L
TL
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000328:Adult; D000917:Antibody Formation; D002648:Child; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D020869:Gene Expression Profiling; D006801:Humans; D008288:Malaria / Q000276:immunology* / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000276:immunology*; D018512:Parasitemia / Q000276:immunology* / Q000517:prevention & control
D000276:Adjuvants, Immunologic; D017780:Malaria Vaccines; C493155:RTS,S-AS02A vaccine