A candidate vaccine against malaria had significant efficacy in a randomized controlled phase III trial in Africa, the RTS,S Clinical Trials Partnership found.
Over 18 months of follow-up, the vaccine -- dubbed RTS,S/AS01 -- averted 941 cases of clinical malaria per 1,000 vaccinations in children 5 through 17 months, according to Lucas Otieno, MD, of the KEMRI–Walter Reed Project in Kombewa, Kenya.
The vaccine also averted 21 cases of severe malaria per 1,000 children vaccinated, Otieno reported at the 6th Multilateral Initiative on Malaria (MIM) Pan-African Conference in Durban, South Africa.
On the other hand, Otieno reported, the vaccine appeared less effective when given to infants 6 through 12 weeks and in both groups vaccine efficacy waned significantly over time (at P<0.01).
Nonetheless, he concluded, the vaccine "shows potential for a role in malaria control in Africa."
Malaria is usually cited as the cause of some 600,000 deaths annually in Africa, most of them in children younger than 5. But a 2012 study suggested the number could be as high as 1.13 million.
The vaccine is one of several under development, but is the furthest along in clinical testing. The drug's developer, GlaxoSmithKline, said in a statement that it will submit a regulatory application to the European Medicines Agency next year.
The trial is being conducted at 11 research centers in seven African countries, where a total of 6,537 infants and 8,923 children have received three doses of either RTS,S/AS01 or a comparator vaccine at 1-month intervals.
The comparator was a meningococcal serogroup C conjugate vaccine and both were delivered together with standard childhood vaccines recommended under the WHO's expanded program on immunization.
After a year's follow-up, Otieno noted, vaccine efficacy against clinical and severe malaria was 56% and 47% respectively in children and 31% and 37% in infants.
After 18 months, he reported, efficacy had fallen. Specifically:
- In children, vaccine efficacy against clinical malaria was 46% overall and significant at all centers and was 36% against severe malaria.
- In infants, efficacy against clinical malaria was 27% but significant in only four of the 11 centers. Efficacy against severe malaria was 15% and nonsignificant.
In children, the vaccine led to significant reductions in malaria and all-cause hospital admission of 42% and 19%, respectively.
Insecticide-treated bed nets, an important malaria preventive measure in Africa, were used by 78% of children and 86% of infants in the trial, Otieno reported.
The vaccine was generally safe and well tolerated, he reported, with no new safety signals.
The investigators had previously reported more cases of meningitis among vaccine recipients than among those getting the comparator drug, but most had a bacterial origin.
The investigators are continuing to monitor the incidence of meningitis closely, Otieno said.
Participants will get a booster shot at 18 months; the impact of that shot will be evaluated when 32-month trial data are available sometime in 2014, the researchers said in a statement.
Primary source: 6th Multilateral Initiative on Malaria Pan-African Conference
Source reference: Otieno L, et al "Efficacy of RTS,S/AS01 vaccine candidate against Malaria in African infants and children 18 months post-primary vaccination series: a phase III randomized, double-blind controlled trial" MIM Pan-African Conference 2013.