According to the World Health Organization (WHO), Malaria causes an estimated 660,000 deaths each year worldwide. Presently, there is no available vaccine for this mosquito-borne disease—only preventative measures, such as bed nets, insecticides, and anti-malarial pills, which have had a limited effect. However, in a considerable step forward, the British drug company GlaxoSmithKline (GSK) announced that they were seeking regulatory approval for the world’s first malaria vaccine: RTS,S.
According to David Poland, senior communications officer at the Program for Appropriate Technology in Health (PATH) Malaria Vaccine Initiative, RTS,S is the scientific name given to this malaria vaccine candidate. The name represents its composition. Poland explained that the aim of the RTS,S vaccine is to trigger the immune system to defend against the deadly malaria parasite Plasmodium falciparum when it enters the bloodstream. It’s designed to prevent the parasite from infecting, maturing, and multiplying in the liver, after which the parasite re-enters the bloodstream and infects red blood cells, leading to the disease symptoms.
“Among the many components found in the RTS,S vaccine, the specific combination of a protein known as the Circumsporozoite protein (CSP) with the hepatitis B antigen is what appears to make it efficacious,” Poland said.
According to Poland, the RTS,S vaccine has been in development for more than 20 years. The vaccine was created in 1987 by scientists working at the GSK laboratories, and it wasn’t until 1995 that the first clinical tests for the vaccine began in the United States. In January 2001, GSK and the PATH Malaria Vaccine Initiative (MVI), with grants from the Bill & Melinda Gates Foundation, entered into a public-private partnership to develop an RTS,S-based vaccine for infants and young children living in malaria-endemic regions in sub-Saharan Africa.
Before the vaccine is introduced, the candidate drug must be assessed for its safety and efficacy profile. This is accomplished through a clinical trial. Specifically, there are three trials (Phase I, II, and III) that evaluate the safety and efficacy by testing the vaccine on various sample sizes. The trials must be designed in consultation with appropriate regulatory authorities and the World Health Organization (WHO). Each phase can be thought of as a pole vault—when the vaccine clears one phase, the bar advances to a higher height, until either the vaccine fails to prove efficacy, or it clears all three phases. According to Poland, the company is at Phase III of the clinical trial.
The Phase III efficacy trial of RTS,S started in May 2009 and is still underway at 11 sites in seven African countries (Burkina Faso, Gabon, Ghana, Kenya, Malawi, Mozambique, and Tanzania) with 15,460 infants and young children participating. According to the MVI, this is the largest malaria vaccine trial in Africa to date. Outlined in the press release published last month by GSK and MVI, researchers enrolled two groups of participants: infants aged 6 to 12 weeks and children aged 5 to 17 months. The participants initially received three doses of either RTS,S or a “control vaccine,” allowing researchers to evaluate the efficacy of the vaccine on a large scale, while continuing to monitor safety and potential side-effects during the 18 months of follow up.
“To date, this trial has indicated that the RTS,S vaccine candidate is safe to administer to young children and provides some protection against malaria disease,” Poland said.
Specifically, the trial has shown that the RTS,S vaccine candidate has an acceptable “safety and tolerability profile” and that based on 18 months of follow-up after their third injection, it reduces clinical malaria cases by 56 per cent in young children 5-17 months of age and by about 31 per cent in infants 6-12 weeks of age. “The potential public health impact is noteworthy,” Poland added.
“The next steps in RTS,S development come in 2014, when we expect to complete this trial and fully analyze the data” Poland explained. “In 2014, the pharmaceutical partner on RTS,S development, GSK, will also be filing for a regulatory opinion with the European Medicines Agency (EMA).”
“If the opinion is supportive, the World Health Organization has indicated that a policy recommendation for the RTS,S malaria vaccine candidate would be possible as early as 2015,” Poland said. “[This will] pave the way for decisions by African nations regarding large-scale implementation of the vaccine through their national immunization programs.”