Promising Results from Malaria Vaccine Trials

In a previous trial, the preerythrocytic malaria vaccine RTS,S given with the AS02A adjuvant protected 30% of children against clinical malaria. Now, two studies (both with partial industry support) add new information about candidate malaria vaccines.

Bejon and colleagues evaluated the efficacy of RTS,S formulated with a more-immunogenic adjuvant system, AS01E. In a double-blind, randomized trial conducted in Kenya and Tanzania, 894 healthy children aged 5 to17 months were randomly assigned to receive three doses of RTS,S/AS01E or rabies (control) vaccine, given intramuscularly at 1-month intervals. Children were followed by active and passive surveillance for clinical episodes of malaria, beginning 2.5 months after the first vaccination (follow-up duration, 4.5 to 10.5 months; mean, 7.9 months). Among the 809 children in the per-protocol analysis, the cumulative incidence of clinical malaria (first or only episode) was 8% in the malaria-vaccine group and 16% in the control group. Efficacy against all clinical episodes of malaria was 56%.

One episode of severe malaria occurred in the malaria-vaccine group versus eight in the control group. The single serious adverse event (a febrile seizure) related to the malaria vaccine was not associated with subsequent neurologic abnormalities. Local adverse events were similar between groups. Levels of anticircumsporozoite antibody varied widely in the malaria-vaccine group and were higher than those seen in the earlier trial with the other adjuvant.

Abdulla and colleagues assessed the feasibility of integrating RTS,S malaria vaccine into the routine infant immunization schedule. In a phase IIB, single-center, double-blind study conducted in Tanzania, 340 infants were randomized to receive three doses of RTS,S (AS02D adjuvant) or hepatitis B vaccine, at 8, 12, and 16 weeks of age. Infants also received oral polio vaccine and a preparation containing diphtheria and tetanus toxoids, whole-cell pertussis vaccine, and Haemophilus influenzae type b vaccine. Malaria infection was cleared with artemether-lumefantrine 4 weeks before active surveillance was started (i.e., 2 weeks before the third vaccine dose).

Local reactions were similar between groups, although low-grade fever was more common in the malaria-vaccine group. Incidence of serious adverse events was also similar between groups, when events caused by malaria were excluded. Antibody responses against all coadministered vaccine antigens were high and similar between groups. Ninety-nine percent of infants who received the malaria vaccine were seropositive for anticircumsporozoite antibodies, versus 1.4% of those who received hepatitis B vaccine. All who received the malaria vaccine (which includes hepatitis B surface antigen) were seroprotected against hepatitis B. Vaccine efficacy for febrile malaria was 59%.