The RTS,S/AS malaria vaccine candidate: A status review

Abstract

The RTS,S/AS malaria vaccine candidate is currently the most advanced in development. It is based on the circumsporozoite protein (CSP) combined with hepatitis B surface antigen. The vaccine is designed to prevent the malaria parasite from infecting the liver where it can mature, multiply, and re-enter the bloodstream, where it infects red blood cells and leads to symptomatic disease. This review documents the development process of the RTS,S/AS malaria vaccine candidate, from preclinical and early clinical trials to the recently concluded Phase III clinical trials. The final results demonstrated that vaccination with the 3-dose primary series reduced clinical malaria cases by 28% in young children and 18% in infants. A booster dose of RTS, S/AS, administered 18 months after the primary series, reduced the number of cases of clinical malaria in young children (aged 5-17 months at first vaccination) by 36% and in infants (aged 6-12 weeks at first vaccination) by 26%. Administration of the booster dose provided longer term protection against clinical malaria in both groups, with 1774 and 983 cases of malaria averted per 1000 children vaccinated in the older (age 5-17 months) and infant (6-12 weeks) age groups, respectively. The vaccine efficacy waned over time following the booster dose and further studies are ongoing to assess long term efficacy and the need for additional doses .The safety profile of the vaccine was acceptable. The vaccine has the potential to make a substantial contribution to malaria control when used in combination with other effective control measures, especially in areas of high transmission