RTS,S/AS01 (RTS,S) is a pediatric vaccine that acts against P. falciparum, the deadliest malaria parasite globally and the most prevalent in Africa. The vaccine is designed to prevent the parasite from infecting the liver, where it can mature, multiply, and infect red blood cells, which can lead to disease symptoms. The vaccine has been shown to significantly reduce malaria, including severe, life-threatening malaria, among children living in settings of moderate to high malaria transmission.
RTS,S was first created in 1987 by scientists working in GSK laboratories. Early clinical development was conducted in collaboration with the Walter Reed Army Institute of Research. In early 2001, GSK and PATH began a collaboration to develop the vaccine for young children living in malaria-endemic regions in sub-Saharan Africa. The Bill & Melinda Gates Foundation provided catalytic funding to PATH for late-stage development of RTS,S between 2001 and 2015.
The pivotal Phase 3 efficacy and safety trial, conducted between 2009 and 2014, involved 15,459 infants and young children and was conducted by 11 clinical research centers in seven African countries (Burkina Faso, Gabon, Ghana, Kenya, Malawi, Mozambique, and Tanzania). The trial demonstrated that among children who received four doses, the vaccine reduced 1 in 4 cases of malaria episodes and 1 in 3 cases of severe malaria cases over a four-year period. The study also showed that, at the trial site with the highest disease burden, more than 6,500 clinical malaria episodes were averted for every 1,000 children fully vaccinated with four vaccine doses.
A study of the longer-term impact of the vaccine, with a focus on severe malaria, was completed in December 2016. The study followed children who participated in the Phase 3 trial at 3 of the 11 research centers for an additional 3 years—a total of 7 years of follow-up. Results showed that the incidence of severe malaria decreased as children got older, regardless of whether children received the vaccine; there was no evidence of rebound of severe malaria following the recommended 4 doses of the vaccine.
 RTS,S Clinical Trials Partnership. Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: Final results of a phase 3, individually randomized, controlled trial. The Lancet. 2015;386(9988): 31-45. doi: 10.1016/S0140- 6736(15)60721-8.
 RTS,S Clinical Trials Partnership. Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose ininfants and children in Africa: Final results of a phase 3, individually randomized, controlled trial. The Lancet. 2015;386(9988): 31-45. doi: 10.1016/S0140-6736(15)60721-8.
 Tinto H, et al. Long-term incidence of severe malaria following RTS,S/AS01 vaccination in children and infants in Africa: an open-label 3-year extension study of a phase 3 randomized control trial. Lancet Infectious Diseases. 2019;doi:10.1016/S1473-3099(19)30300-7; see also Dicko A,Greenwood B. Malaria vaccination and rebound malaria. Lancet Infectious Diseases. 2019;doi:10.1016/S1473-