RTS, S Malaria Vaccine Candidate Study Shows Success

Malawi team in Malaria vaccine study

A study on Malaria vaccine candidate has registered positive results, now thought to be a break through in the fight against Malaria in endemic regions in sub-Saharan Africa.

Final results from a large-scale Phase III trial of the RTS, S Malaria vaccine candidate including a booster dose shows that it can protect children and infants from clinical malaria for at least three years after first vaccination. 

Eleven research centres in 7 African countries including Area 18 Health Centre in Lilongwe conducted the efficacy and safety trial where the evaluation was in the context of the existing malaria control measures such as incectcide treated bed nets which were used by approximately 80% of the 15, 459  participants.

Prof. Francis Martinson

A Principle Investigator in the trial in Malawi, who is also UNC Project Country Director, Professor Francis Martinson says the latest results to the end of study demonstrates that RTS, S followed by a booster dose of RTS, S administered 18 months after primary schedule, reduced number of cases of clinical malaria in children aged 5-17 months by 36% and by 26% to Infants aged 6-12 weeks.

However without a booster dose the reduction in clinical malaria cases were between 28% and 18% in children and infants respectively.

"Today we have a vaccine which has shown to be effective in one way or the other, the vaccine had showed the efficacy of 36% in the order age group of 5 to 17 months so we are very happy because this is the first time that a vaccine has show some efficacy said Prof. Martinson who added that this is a progress and it is a first vaccine against the parasite."

"We believe this is a beginning of something big, we believe that this is a beginning is something good thats the vaccine hopefully will be improved over the years for us to also have something that works better than something we have seen."

Prof. Francis Martinson
(second from left) Next to him 
is Dr. Portia Kamthunzi 
(a Lead Physician/ Investigator 
of Records

On the recorded percentage efficacy against severe malaria to the end of the study period wich did not even reach 50%, he said If we look carefully the 36% sounds small but this is on top of 80% of bed net usage and that translates to 1774 cases of malaria prevented per every 1000 children. So it looks small but to have over a thousand cases of malaria prevented for every thousand people or children is not a mean achievement. It means at least everybody has been spared in one episode of going to the hospital and therefore the mother of that child is in a great relief because we all know what it means to get malaria and how our mothers suffer through the process for these kids.

Currently the data has been passed on to the European Medicines Agency, where they are looking at it and if they are happy with it they will refer the information to the WHO, who will also look at the results. 

"If the WHO will be happy with the information hopefully they will recommend to African governments to include the vaccine in their EPI programmes." said Prof. Francis Martinson

It is intended to complement and not supplement other malaria control interventions.

The results are important as infants are considered to be the primary target for RTS, S immunisation.

The Sumary details of the research 

Prof. Francis Martinson (middle) and Dr. Portia
Kamnthunzi to his right 

We are pleased to announce that the Final results from a large-scale Phase III trial of the RTS, S malaria vaccine candidate, including the impact of a booster dose, show that the vaccine candidate helped protect children and infants from clinical malaria for at least three years after 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 study and in infants (aged6-12 weeks at first vaccination) by 26% to the end of the study. Efficacy decreased over time in both age groups. Without the booster dose, the vaccine 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, an average of 1,774 cases of clinical malaria were prevented for every 1,000 children vaccinated across the trial sites, at the end of the study. For infants aged 6-12 weeks age category, who received a booster dose, 983 cases of clinical malaria, on average, were prevented for every 1,000 infants vaccinated. 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 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.

Eleven research centres in seven African countries 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).

Safety

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.

These data was part of submissions to the European Medicines Agency (EMA) in July 2014. The European Medicines Agency (EMA) is currently reviewing the regulatory application for RTS,S through the Art. They will also be shared with appropriate World Health Organisation (WHO) committees. All these agencies are expected to play various roles in the registration of the vaccine for use in future. A positive opinion from the EMAs Committee for Medicinal Products for Human Use, together with a potential policy recommendation from the World Health Organisation (anticipated by the end of 2015), would be the basis for licensure applications to National Regulatory Authorities in sub-Saharan African countries. If positive, these regulatory decisions would help pave the way for the introduction of RTS, S through African national immunisation programmes. If RTS, S is approved, GSK has committed to making the vaccine available at a not-for-profit price.