Malaria vaccine candidate less effective in infants

New findings from an ongoing Phase III malaria vaccine trial in Africa suggest that the candidate, RTS,S, reduces the incidence of clinical malaria and severe malaria by a modest 31.3% and 36.6%, respectively, among children 6-12 weeks of age. Published online on Nov. 9 in the New England Journal of Medicine, the results nonetheless find that the efficacy of RTS,S was less than that reported last year for older children enrolled in the same trial (see VAX  Nov. 2011 Spotlight article, A Shot at Fighting Malaria). It also appears to be lower than  previously reported in a smaller Phase II trial. 

Mary Hamel, a medical epidemiologist at the US Centers for Disease Control and Prevention and a principal investigator at one of the trial’s clinical research centers in Kisumu, Kenya, said researchers should gain some clarity when data from all the sites where the study was conducted are released in the next year or two. “We may find that by pooling the data across the 11 trial sites, differences in vaccine efficacy by malaria transmission intensity were masked,” Hamel says. “Most malaria cases in this analysis were from areas of very high transmission. Efficacy in areas of low or moderate malaria transmission may be higher, consistent with the Phase II trial.” 

Developed and manufactured by GlaxoSmithKline (GSK) Biologicals, RTS,S contains a protein found on the surface of the P. falciparum sporozoite—the form of the parasite transmitted from mosquitoes to people—linked to hepatitis B vaccine antigen. It is formulated with AS01, an adjuvant manufactured by GSK.

The RTS,S candidate was co-administered with two licensed vaccines: a pentavalent vaccine against diphtheria, tetanus, pertussis, hepatitis B and Hemophilus influenzae type B, and a polio vaccine.  Scientists suggest that the co-administration of the licensed vaccines—including the Hep B antigen, which was effectively delivered twice—may have compromised the immune response to the RTS,S candidate. Hamel adds that infants have immature immune systems that respond less vigorously to vaccination, and that their responses might have been further compromised by antibodies against the sporozoites passed down by their mothers. Lower vaccine efficacy could also be associated with higher-transmission regions, but that will only be known when the site-specific analysis is completed.

The fate of RTS,S remains unclear. The PATH Malaria Vaccine Initiative, which financed most of the research with a $200 million grant from the Bill & Melinda Gates Foundation, hasn’t yet announced any decision. “The efficacy came back lower than we had hoped, but developing a vaccine against a parasite is a very hard thing to do,” said Bill Gates in a statement on PATH’s website. “The trial is continuing, and we look forward to getting more data to help determine whether and how to deploy this vaccine.” —Regina McEnery