International African Vaccinology Conference, Cape Town, South Africa-Results from a pivotal, large-scale Phase III trial, published online today in the New England Journal of Medicine, show that the RTS,S malaria vaccine candidate can help protect African infants against malaria. When compared to immunization with a control vaccine, infants (aged 6-12 weeks at first vaccination) vaccinated with RTS,S had one-third fewer episodes of both clinical and severe malaria and had similar reactions to the injection. In this trial, RTS,S demonstrated an acceptable safety and tolerability profile.
Eleven African research centres in seven African countries are conducting this trial, together with GlaxoSmithKline (GSK) and the PATH Malaria Vaccine Initiative (MVI), with grant funding from the Bill & Melinda Gates Foundation to MVI.
Dr. Salim Abdulla, a principal investigator for the trial 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. An effective malaria vaccine would be a welcome addition to our tool kit, and we've been working toward this goal with this RTS,S trial. 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 trial 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 trial 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 trial 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 from the trial 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."
There was no increase in overall reporting of serious adverse events (SAEs) 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.
Sir Andrew Witty, CEO, GSK said: "While the efficacy seen is lower than last year, we believe these results confirm that RTS,S can help provide African babies and young children with meaningful protection against malaria. They take us another important step forward on the journey towards having a new intervention available against this disease, which is a huge burden on the health and economic growth of Africa. We remain convinced that RTS,S has a role to play in tackling malaria and we will continue to work with our partners and other stakeholders to better understand the data and to define how the vaccine could best be used to provide public health benefit to children in malaria endemic areas in Africa."
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. My congratulations go out to the team at GSK and to the African research centres for their exemplary conduct of this trial."