RTS,S — trade name Mosquirix — is a recombinant protein-based malaria vaccine. Approved for use by European regulators in July 2015, it is not only the world's first licensed malaria vaccine, but the first vaccine licensed for use against a parasitic disease of any kind. Funded in recent years by the PATH Malaria Vaccine Initiative and the Bill and Melinda Gates Foundation, it began development under the U.S. military at the Walter Reed Army Institute of Research in the late 1980s. Although its efficacy is currently judged to be only 27 to 46%, it is nevertheless considered to be a significant advance in the worldwide campaign against malaria.
A completely effective vaccine is not yet available for malaria, although several vaccines are under development. 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. RTS,S is one of several potential vaccines under development that target the pre-erythrocytic stage of the disease. Among them, 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, further research was considered necessary to improve the effectiveness of the vaccine.
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 amount 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.
GSK submitted an application for a marketing license with the European Medicines Agency (EMA) in July, 2014. The new vaccine has the backing of the UN’s Swiss-based WHO which states that it will recommend the use of RTS,S for use starting in 2015, providing it gets approval.
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.
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 boost 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.
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