The RTS,S trial vaccine results

Final results from a large-scale Phase III trial of the RTS,S malaria vaccine candidate, including the impact of a booster dose, published today in The Lancet, show that the vaccine candidate helped protect children and infants from clinical malaria for at least three years after first vaccination.

The eleven research centres in seven African countries2 including KEMRI| Wellcome Trust in Kilifi, KEMRI & CDC in Kombewa Kisumu and KEMRI Walter Reed in Siaya conducted the efficacy and safety trial, in partnership with GSK and the PATH Malaria Vaccine Initiative (MVI), with grant funding from the Bill & Melinda Gates Foundation to MVI. The trial, started in March 2009 and concluded in January 2014, enrolled 15,459 participants, in two age categories: children (aged 5-17 months at first vaccination) and infants (aged 6-12 weeks at first vaccination).

The latest results demonstrated that vaccination with RTS,S, followed by a booster dose of RTS,S administered 18 months after the primary schedule, reduced the number of cases of clinical malaria in children (aged 5-17 months at first vaccination) by 36% to the end of the study1 (over an average follow-up of 48 months across trial sites) and in infants (aged 6-12 weeks at first vaccination) by 26% to the end of the study (over an average follow-up of 38 months across trial sites). Efficacy decreased over time in both age groups. Without the booster dose, the 3-dose primary schedule reduced clinical malaria cases by 28% in children and 18% in infants to the study end. The efficacy of RTS,S was evaluated in the context of existing malaria control measures, such as insecticide treated bed nets, which were used by approximately 80% of the children and infants in the trial.

For children in the 5-17 month age category who received a booster dose 18 months after the primary schedule, an average of 1,774 cases of clinical malaria were prevented for every 1,000 children vaccinated across the trial sites, over an average of 48 months of follow-up. For infants aged 6-12 weeks at first vaccination with RTS,S, who received a booster dose, 983 cases of clinical malaria, on average, were prevented for every 1,000 infants vaccinated across trial sites over an average of 38 months of follow-up. More cases were averted in areas of higher malaria transmission. In the absence of a booster dose, 1,363 cases of clinical malaria were prevented, on average, for every 1,000 children aged 5-17 months at first vaccination and 558 cases for every 1,000 infants aged 6-12 weeks at first vaccination to the end of the study

Statistically significant efficacy against severe malaria to the end of the study period was observed only in children who received the booster dose. There was indication of increased risk for severe malaria in children who did not receive the booster dose, compared to those in the control group.
RTS,S continued to display an acceptable safety and tolerability profile during the entire study period.
The incidence of fever in the week after vaccination was higher in children who received RTS,S than in those receiving control vaccine. In some children who experienced fever, the febrile reaction was accompanied by generalized convulsions, but all those affected fully recovered within seven days.

The meningitis signal previously reported remains in the older age category, including two cases reported after the booster dose of RTS,S. This could be a chance finding, as comparisons were made across groups for many different diseases, and because some of these cases happened years after vaccination without any obvious relationship to vaccination. The occurrence of meningitis will be followed closely during Phase IV studies, if RTS,S is licensed.