RTS,S/AS01 (trade name Mosquirix) is a recombinant protein-based malaria vaccine.
Approved for use by European regulators in July 2015, it is the world's first licensed malaria vaccine and also the first vaccine licensed for use against a human parasitic disease of any kind. The RTS,S vaccine was conceived of and created in the late 1980s by scientists working at SmithKline Beecham Biologicals (now GlaxoSmithKline Vaccines) laboratories in Belgium. The vaccine was further developed through a collaboration between GSK and the Walter Reed Army Institute of Research and has been funded in part by the PATH Malaria Vaccine Initiative and the Bill and Melinda Gates Foundation. Its efficacy ranges from 26 to 50% in infants and young children. On 23 October 2015, the World Health Organization's Strategic Advisory Group of Experts on Immunization (SAGE) and the Malaria Policy Advisory Committee (MPAC) jointly recommended a pilot implementation of the vaccine in Africa.
This pilot project for vaccination has been launched on 23 April 2019 in Malawi, on 30 April 2019 in Ghana, and on 13 September 2019 in Kenya.
Potential malaria vaccines have been an intense area of research since the 1960s. SPf66 was tested extensively in endemic areas in the 1990s, but clinical trials showed it to be insufficiently effective. Other vaccine candidates, targeting the blood-stage of the malaria parasite's life cycle, have also been insufficient on their own. Among several potential vaccines under development that target the pre-erythrocytic stage of the disease, RTS,S has shown the most promising results so far.
The RTS,S-based vaccine formulation had previously been demonstrated to be safe, well tolerated, immunogenic, and to potentially confer partial efficacy in both malaria-naive and -experienced adults as well as children.
In November 2012, findings from a Phase III trial of RTS,S reported that it provided modest protection against both clinical and severe malaria in young infants. In October 2013, GlaxoSmithKline (GSK) reported that the RTS,S vaccine reduced the number of cases amongst young children by almost 50 percent and among infants by around 25 percent, following the conclusion of an 18-month clinical trial. Data showed the protective effect after the 18 months, however, was less than had previously been seen after 12 months.
The EMA approved the RTS,S vaccine in July 2015, with a recommendation that it be used in Africa for babies at risk of getting malaria. RTS,S was the world's first malaria vaccine to get approval for this use. After additional regulatory decisions by the World Health Organization, and individual African country governments, a "roll out" of the product could come as early as 2017.
Preliminary research suggests that delayed fractional dosing could increase the vaccine's efficacy up to 86%.
On 17 November 2016, WHO announced that the RTS,S vaccine would be rolled out in pilot projects in 3 countries in sub-Saharan Africa. The pilot programme, coordinated by WHO, will assess the extent to which the vaccine’s protective effect shown in advanced clinical trials can be replicated in real-life settings. Specifically, the programme will evaluate the feasibility of delivering the required 4 doses of the vaccine; the impact of the vaccine on lives saved; and the safety of the vaccine in the context of routine use.
Vaccinations by the ministries of health of Malawi, Ghana, and Kenya began in April and September 2019 and target 360 000 children per year in areas where vaccination would have the highest impact. The results are planned to be used by the World Health Organization to advise about a possible future deployment of the vaccine.
Components and mechanism
The RTS,S vaccine was engineered using genes from the repeat and T-cell epitope in the pre-erythrocytic circumsporozoite protein (CSP) of the Plasmodium falciparum malaria parasite and a viral envelope protein of the hepatitis B virus (HBsAg), to which was added a chemical adjuvant (AS01) to increase the immune system response. Infection is prevented by inducing humoral and cellular immunity, with high antibody titers, that block the parasite from infecting the liver.
^Regules JA, Cicatelli SB, Bennett JW, et al. (2016). "Fractional Third and Fourth Dose of RTS,S/AS01 Malaria Candidate Vaccine: A Phase 2a Controlled Human Malaria Parasite Infection and Immunogenicity Study". J. Infect. Dis. 214 (5): 762–71. doi:10.1093/infdis/jiw237. PMID27296848.
Wilby, K. J.; Lau, T. T.; Gilchrist, S. E.; Ensom, M. H. (2012). "Mosquirix (RTS,S): A Novel Vaccine for the Prevention of Plasmodium falciparum Malaria". Annals of Pharmacotherapy. 46 (3): 384–93. doi:10.1345/aph.1Q634. PMID22408046.
Asante, Kwaku Poku; et al. (2011). "Safety and efficacy of the RTS,S/AS01E candidate malaria vaccine given with expanded-programme-on-immunisation vaccines: 19 month follow-up of a randomised, open-label, phase 2 trial". The Lancet Infectious Diseases. 11 (10): 741–9. doi:10.1016/S1473-3099(11)70100-1. PMID21782519.