Photo by Caitlin Kleiboer
The malaria vaccine candidate RTS,S/AS01 is somewhat effective in young African children for up to 4 years after vaccination, according to final data from a phase 3 trial.
The vaccine proved more effective against clinical and severe malaria in children than in young infants, but efficacy waned over time in both age groups.
On the other hand, a booster dose of RTS,S/AS01 increased the average number of malaria cases prevented in children and infants.
“Despite the falling efficacy over time, there is still a clear benefit from RTS,S/AS01,” said Brian Greenwood, MD, of the London School of Hygiene & Tropical Medicine in the UK.
“An average 1363 cases of clinical malaria were prevented over 4 years of follow-up for every 1000 children vaccinated, and 1774 cases in those who also received a booster shot. Over 3 years of follow-up, an average 558 cases were averted for every 1000 infants vaccinated, and 983 cases in those also given a booster dose.”
Dr Greenwood and his colleagues disclosed these data in The Lancet. The research was funded by GlaxoSmithKline Biologicals SA, the company developing RTS,S/AS01, and the PATH Malaria Vaccine Initiative.
The trial included 15,459 young infants (aged 6 weeks to 12 weeks at first vaccination) and children (5 months to 17 months at first vaccination) from 11 sites across 7 sub-Saharan African countries (Burkina Faso, Gabon, Ghana, Kenya, Malawi, Mozambique, and United Republic of Tanzania) with varying levels of malaria transmission.
Earlier results from this trial, at 18 months of follow-up, showed efficacy of about 46% against clinical malaria in children and around 27% among young infants. Vaccine efficacy is defined as the reduction in the incidence of disease among participants who receive the vaccine compared to the incidence among participants who do not.
Dr Greenwood and his colleagues followed the infants and children for a further 20 to 30 months, respectively, and assessed the impact of a fourth booster dose.
Participants were each vaccinated 3 times with RTS,S/AS01, with or without a booster dose 18 months later, or given 4 doses of a comparator vaccine (control group).
In children who received 3 doses of RTS,S/AS01 plus a booster, the number of clinical episodes of malaria at 4 years was reduced by just over a third (36%). This is a drop in efficacy from the 50% protection against malaria seen in the first year.
Without a booster dose, the vaccine was not significantly effective against severe malaria in this age group. However, in children given a booster dose, the overall protective efficacy against severe malaria was 32% and 35% against malaria-associated hospitalizations.
In infants who received 3 doses of RTS,S/AS01 plus a booster, the vaccine reduced the risk of clinical episodes of malaria by 26% over 3 years of follow-up. There was no significant protection against severe disease in infants.
Meningitis occurred more frequently in children given RTS,S/AS01 than in children given the control vaccine. There were 11 cases of meningitis among children who received a booster, 10 cases among children who did not receive a booster, and 1 case among children in the control group.
RTS,S/AS02 produced more adverse reactions than the control vaccines. Convulsions following vaccination, although uncommon, occurred more frequently in children who received RTS,S/AS01. The incidence of other serious adverse events was similar in all the groups.
“The European Medicines Agency (EMA) will assess the quality, safety, and efficacy of the vaccine based on these final data,” Dr Greenwood said. “If the EMA gives a favorable opinion, WHO could recommend the use of RTS,S/AS01 as early as October this year. If licensed, RTS,S/AS01 would be the first licensed human vaccine against a parasitic disease.”
