RTS,S/AS01E (RTS,S) is the first malaria vaccine that has been shown in Phase 3 trials to provide partial protection against malaria in young African children. The vaccine acts against Plasmodium falciparum, the deadliest species of the malaria parasite globally and the most prevalent in Africa. RTS,S targets the pre-erythrocytic (liver) stage of the lifecycle of P. falciparum, and is designed to prevent the malaria parasite from infecting, maturing, and multiplying in the liver, after which the parasite would normally re-enter the bloodstream and infect red blood cells, leading to disease symptoms. RTS,S has been developed over more than three decades by GSK, including through a collaboration, begun in 2001, with PATH's Malaria Vaccine Initiative.
RTS,S is the first malaria vaccine to receive a positive scientific opinion from the European Medicines Agency (EMA), whose Committee for Medicinal Products for Human Use (CHMP) agreed by consensus that the benefits of vaccination with RTS,S outweighed the risks.1 Subsequently, the World Health Organization (WHO) recommended pilot implementation of RTS,S in young children, in settings of moderate-to-high parasite transmission in Africa.2
Once preparations are completed, RTS,S will be provided to young children through routine immunization programs, in selected areas of Ghana, Kenya, and Malawi. It will be evaluated for use as a complementary malaria control tool that could be added to (and not replace) the core package of WHO-recommended preventive, diagnostic, and treatment measures. Concurrent with the pilot implementation, PATH and GSK are exploring how best to ensure the longer-term supply of the vaccine.
RTS,S is the first, and to date, the only vaccine to show a protective effect against malaria among young children in a Phase 3 trial, which was conducted over 5 years (from 2009 to 2014), and enrolled 15,459 young children and infants in 7 sub-Saharan African countries.2 Among children aged 5–17 months who received 4 doses of RTS,S, the vaccine prevented approximately 4 in 10 (39%) cases of malaria over 4 years of follow-up and about 3 in 10 (29%) cases of severe malaria, with significant reductions also seen in overall hospital admissions as well as in admissions due to malaria or severe anemia.3 The vaccine also reduced the need for blood transfusions, which are required to treat life-threatening malaria anemia, by 29%.
RTS,S was developed over three decades by GSK, including through a collaboration—begun in 2001—with PATH’s Malaria Vaccine Initiative and a network of African research centers.
1. European Medicines Agency (EMA). Mosquirix, Summary for the public. 2015. Available at http://bit.ly/2oWfXeh.
2. World Health Organization. Weekly Epidemiological Record. 2016; 91(4): 33–52. Available at: www.who.int/wer/2016/wer9104/en.
3. 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: 31-45.
Articles on Phase 3 trials
Otieno L, Oneko M, Otieno W, Abuodha J, Owino E, et al. Safety and immunogenicity of RTS,S/AS01 malaria vaccine in infants and children with WHO stage 1 or 2 HIV disease: a randomized, double-blind, controlled trial. The Lancet Infectious Diseases. 2016;16(10): 1134-1144.
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: 31-45.
Ajua A, Lell B, Agnandji ST, Asante KP, Owusu-Agyei S, et al. The effect of immunization schedule with the malaria vaccine candidate RTS,S/AS01E on protective efficacy and anti-circumsporozoite protein antibody avidity in African infants. Malaria Journal. 2015;14: 72.
RTS,S Clinical Trials Partnership. Efficacy and safety of the RTS,S/AS01 malaria vaccine during 18 months after vaccination: a phase 3 randomized, controlled trial in children and young infants at 11 African sites. PLoS Medicine. 2014;11(7): e1001685. doi:10.1371/journal.pmed.1001685.
RTS,S Clinical Trials Partnership. A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants. New England Journal of Medicine. 2012; 367:2284-2295.
RTS,S Clinical Trials Partnership. First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children. New England Journal of Medicine. 2011; 365:1863-1875.
Articles on Phase 2 trials
Olotu A, Fegan G, Wambua J, Nyangweso G, Leach A, et al. Seven-year efficacy of RTS,S/AS01 malaria vaccine among young African children. New England Journal of Medicine. 2016; 374:2519-2529.
Abdulla S, Nahya S, Machera F, Kamata R, Juma O, et al. Randomized, controlled trial of the long term safety, immunogenicity and efficacy of RTS,S/AS02D malaria vaccine in infants living in a malaria-endemic region. Malaria Journal. 2013;12:11.
Aide P, Dobaño C, Sacarlal J, Aponte JJ, Mandomando I, et al. Four year immunogenicity of the RTS,S/AS02A malaria vaccine in Mozambican children during a phase IIb trial. Vaccine. 2011;29(35): 6059-6067.
Campo JJ, Dobaño C, Sacarlal J, Guinovart C, Mayor A, et al. Impact of the RTS,S malaria vaccine candidate on naturally acquired antibody responses to multiple asexual blood stage antigens. PLoS ONE. 2011;6(10): e25779. doi:10.1371/journal.pone.0025779.
Ansong D, Asante KP, Vekemans J, Owusu SK, Owusu R, et al. T cell responses to the RTS,S/AS01E and RTS,S/AS02D malaria candidate vaccines administered according to different schedules to Ghanaian children. PLoS ONE. 2011;6(4): e18891.
Agnandji ST, Fendel R, Mestré M, Janssens M, Vekemans J, et al. Induction of Plasmodium falciparum-specific CD4+ T cells and memory B cells in Gabonese children vaccinated with RTS,S/AS01E and RTS,S/AS02D. PLoS ONE. 2011;6(4): e18559.
Aide P, Aponte JJ, Renom M, Nhampossa T, Sacarlal J, et al. Safety, immunogenicity and duration of protection of the RTS,S/AS02Dmalaria vaccine: one year follow-up of a randomized controlled phase I/IIb trial. PLoS ONE. 2010;5(11): e13838.
Sacarlal J, Aide P, Aponte JJ, Renom M, Leach A, et al. Long-term safety and efficacy of the RTS,S/AS02A malaria vaccine in Mozambican children. The Journal of Infectious Diseases. 2009;200(3): 329-336.
Bejon P, Lusingu J, Olotu A, Leach A, Lievens M, et al. Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age. New England Journal of Medicine. 2008; 359: 2521-2532.
Abdulla S, Oberholzer R, Juma O, Kubhoja S, Machera F, et al. Safety and immunogenicity of RTS,S/AS02D malaria vaccine in infants. New England Journal of Medicine. 2008; 359:2533-2544.
Alonso PL, Sacarlal J, Aponte JJ, Leach A, Macete E, et al. Duration of protection with RTS,S/AS02A malaria vaccine in prevention of Plasmodium falciparum disease in Mozambican children: single-blind extended follow-up of a randomized controlled trial. The Lancet. 2005;366(9502): 2012-2018.
Bojang KA, Milligan PJ, Pinder M, Vigneron L, Alloueche A, et al. Efficacy of RTS,S/AS02 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia: a randomized trial. The Lancet. 2001;358(9297): 1927-34.