Malaria Vaccine R21 Shows 68-75% Efficacy in Phase 3 Trial of Children in 4 African Countries

Malaria is a leading cause of child death in sub-Saharan Africa. A team led by Mehreen S. Datoo at the Jenner Institute at the University of Oxford in the United Kingdom published in The Lancet the phase 3 results of the vaccine R21/Matrix-M given to children in four African countries. The vaccine targets the circumsporozoite protein on the surface of the malaria parasite sporozoite and adds the adjuvant Matrix-M.

Double-Blind Phase 3 With a Rabies Vaccine as Control

The researchers divided children aged 5 to 36 months 2:1 to receive R21/Matrix-M or a control vaccine (a licensed rabies vaccine) in three doses 4 weeks apart, followed by a booster 12 months later. Areas with seasonal transmission and areas with year-round transmission were analysed separately, and the primary endpoint was efficacy against first clinical malaria from 14 days after the third dose through 12 months. A total of 4,878 children received a first dose, and 4,644 were included in the analysis.

Efficacy was 75% in the seasonal area and 68% in the year-round transmission area. It was highest in the 5-to-17-month group, at 79% and 75%, respectively, and the higher the antibody level against the NANP repeat sequence of the parasite protein, the greater the efficacy. The common adverse events were fever (46.7%) and injection-site pain (18.6%); there was no significant difference between the two groups in the frequency of adverse events of special interest or serious adverse events, and there were no vaccine-related deaths.

Significance and Limits

Because it is a vaccine that can be mass-produced cheaply, it is judged to be able to help ease supply shortages. However, efficacy declined gradually during the 12 months of follow-up, and longer follow-up is needed to confirm the effect on reducing severe malaria and death. The manufacturer, the Serum Institute of India, paid part of the research costs.