The malaria vaccine RTS,S/AS01 was more effective among children than infants, but it had modest levels of efficacy overall and prevented a significant amount of clinical and severe malaria cases, according to results from an ongoing trial published in PLOS Medicine.
The RTS,S Clinical Trials Partnership randomly assigned 6,537 infants, aged 6 to 12 weeks, and 8,923 children, aged 5 to 17 months, to three doses of RTS,S/AS01 (Mosquirix, GlaxoSmithKline) or a comparator vaccine. Researchers conducted an 18-month follow-up. Study participants who received a comparator vaccine served as the control and were administered VeroRab (Sanofi-Pasteur) or Menjugate (Novartis). The study was conducted from March 2009 to January 2011 across 11 sites in seven African countries.
Overall, 77% of children and 92% of infants received the full three-dose regimen. Those who received at least one dose were categorized into an “intention to treat” group.
Among the intention to treat group, vaccine efficacy was 45% (95% CI, 41-49) for the 20 months after the first dose.
Among children who received three doses, vaccine efficacy against clinical malaria was 46% (95% CI, 42-50) 18 months after vaccination. Malaria incidence was reduced by 68% for the first 6 months after vaccination; 41% for months 7 to 12, and 26% for months 13 to 18. Lower vaccine efficacy was associated with moderate anemia at baseline (P=.04).
Vaccine efficacy against parasitemia in children was 31%. Efficacy was 36% against severe malaria; 42% against malaria hospitalization; and 19% against all-cause hospitalization.
During the 18-month follow-up period, the number of averted malaria hospitalizations ranged from 0 to 138 per 1,000 children, with an average of 43 across all sites. All-cause hospitalizations ranged from –3 to 132 per 1,000 children, with an average of 52 across all sites.
Regarding infants, vaccine efficacy against clinical malaria was 27% (95% CI, 20-32). Clinical malaria incidence was reduced by 47% for the first 6 months after vaccination; 23% for months 7 to 12; and 12% for months 13 to 18.
Among infants who received at least one dose of RTS,S/AS01, an average of 449 cases of clinical malaria were averted per 1,000 infants. No significant protection against severe malaria, malaria hospitalization or all-cause hospitalization was observed.
Post-vaccination anti-circumsporozoite antibody geometric mean titers ranged from 348 EU/mL to 787 EU/mL across sites among children; and from 117 endotoxin units/mL to 335 endotoxin units/mL among infants.
Vaccine efficacy decreased with time among both age groups.
Serious adverse events were less frequent among children vaccinated with RTS,S/AS01 compared with children in the control (18.6% vs. 22.7%). There was no significant difference between infants. Meningitis was a reported serious adverse event among 16 children and nine infants in the RTS,S/AS01 group and one child and three infants in the control group.
“During 18 months of follow-up, RTS,S/AS01 prevented many cases of clinical and severe malaria across the 11 sites in the trial. Despite its lower efficacy in young infants, RTS,S/AS01 also prevented a substantial number of cases of clinical malaria in young infants. Translated to the population at risk of malaria, reductions in clinical cases on this scale as a result of vaccination with RTS,S/AS01 would have a major public health impact,” the researchers concluded.
Disclosure: The study was funded by GlaxoSmithKline Biologicals, the vaccine developer and manufacturer.