The first complete set of results from an on-going pivotal, large-scale Phase III study of a new malaria vaccine candidate--RTS,S-- in children aged 5 to 17 months and combined data for severe malaria in the first 250 cases from those aged 6 weeks to 17 months were published online in the New England Journal of Medicine. The data confirms that this vaccine candidate reduces both clinical and severe malaria by approximately one-third in African infants (aged 6-12 weeks at first vaccination).
RTS,S is a scientific name given to the malaria vaccine candidate which aims to trigger the immune system to defend against Plasmodium falciparum malaria parasite when it first enters the human host’s bloodstream and/or when the parasite infects liver cells. It is designed to prevent the parasite from infecting, maturing, and multiplying in the liver, after which time the parasite would re-enter the bloodstream and infect red blood cells, leading to disease symptoms. In the Phase III efficacy study, RTS,S is administered in three doses, one month apart. A booster dose administered 18 months after the third dose is also being studied.
Dr. Salim Abdulla, a principal investigator for the study from the Ifakara Health Institute, Tanzania, said: “We’ve made significant progress in recent years in our battle against malaria, but the disease still kills 655,000 people a year—mainly children under five in sub-Saharan Africa. This study indicates that RTS,S can help to protect young babies against malaria. Importantly, we observed that it provided this protection in addition to the widespread use of bed nets by the study participants.”
When administered along with standard childhood vaccines, the efficacy of RTS,S in infants aged 6 to 12 weeks (at first vaccination) against clinical and severe malaria was 31% and 37%, respectively, over 12 months of follow-up after the third vaccine dose. Insecticide-treated bed nets were used by 86% of the study participants, which demonstrated that RTS,S provided protection beyond existing malaria control interventions. The efficacy observed with RTS,S last year in children aged 5-17 months of age against clinical and severe malaria was 56% and 47%, respectively. Follow-up in this Phase III study will continue and is expected to provide more data for analyses to better understand the different findings between the age categories.
Dr. Abdulla added: “The efficacy is lower than what we saw last year with the older 5-17 month age category, which surprised some of us scientists at the African trial sites. It makes us even more eager to gather and analyze more data to determine what factors might influence efficacy against malaria and to better understand the potential of RTS,S in our battle against this devastating disease. We were also glad to see that the study indicated that RTS,S could be administered to young infants along with standard childhood vaccines and that side effects were similar to what we would see with those vaccines.”
As far as safety of this new vaccine candidate is concerned, there was no increase in overall reporting of serious adverse events between the infants vaccinated with the RTS,S malaria vaccine candidate and infants in the control group, which received a comparator vaccine. Side effects primarily included local injection site reactions, which were less frequent following RTS,S vaccinations compared to the DTP-HepB/Hib vaccine. Fever was reported more frequently following RTS,S vaccinations than the control vaccine group (30.6% versus 21.1% of vaccine doses,
respectively). Two new cases of meningitis were reported in the 6-12 week-old infant age category in addition to the 9 reported last year; one in the RTS,S group and one in the control vaccine group. Further analysis revealed a bacterial cause of the meningitis in 7 of the 11 cases.
Eleven African research centres in seven African countries are conducting this study, together with GlaxoSmithKline (GSK) and the PATH Malaria Vaccine Initiative (MVI), with more than US$200 million grant funding from the Bill & Melinda Gates Foundation to MVI. MVI contributes financial, scientific, managerial, and field expertise to the development of RTS,S. GSK takes the lead in the overall development of RTS,S and has invested more than $300 million to date and expects to invest more than $200 million before the completion of the project. GSK and MVI are committed to making this vaccine available to those who need it most, should it be approved and recommended for use.
David Kaslow, Director of the PATH Malaria Vaccine Initiative, said: “Determining the role of RTS,S in Africa will depend on analyses of additional data. We are now an important step closer to that day. Success in developing malaria vaccines depends on many factors: at the top of the list are partnerships and robust evidence, coupled with an understanding that different combinations of tools to fight malaria will be appropriate in different settings in malaria-endemic countries.”
Follow-up in this Phase III study will continue to provide more data for analyses to better understand the different findings between the age categories, as well as the vaccine candidate’s efficacy in different malaria parasite transmission settings. More data on the longer-term efficacy of the vaccine during 30 months of follow-up after the third dose, and the impact of a booster dose are expected to be publicly available at the end of 2014.
If the required regulatory approvals are obtained and public health information, including safety and efficacy data from the Phase III programme, is deemed satisfactory, the World Health Organization has indicated that a policy recommendation for the RTS,S malaria vaccine candidate is possible as early as 2015, paving the way for decisions by African nations regarding large-scale implementation of the vaccine through their national immunisation programmes. An effective vaccine for use alongside other measures such as bed nets and anti-malarial medicines would represent a decisive advance in malaria control.
Citizen News Service (CNS)