Protective effects of RTS,S malaria vaccine candidate

An team of researchers has used cutting edge genomic methods to uncover key biological insights that help explain the protective effects of the world's most advanced malaria vaccine candidate, RTS,S/AS01 (RTS,S).

Applying highly sensitive sequencing technology to more patient samples than previously tested, researchers from Broad Institute of MIT and Harvard, the Harvard T.H. Chan School of Public Health, and Fred Hutchinson Cancer Research Center were able to determine that genetic variation in the protein targeted by RTS,S influences the vaccine's ability to ward off malaria in young children.

This is an example of the benefits of applying genomics to a real world problem of global health importance, said Dyann Wirth, who along with Peter Gilbert of Fred Hutchinson Cancer Research Center, led the study that could inform future vaccine development.

Malaria is a global health threat responsible for hundreds of millions of infections and more than half a million deaths annually in tropical and subtropical regions of the world. The disease is caused by intracellular protozoan parasites from the genus Plasmodium, which are transmitted to humans by mosquito vectors.

Through a collaboration with the vaccine division of the healthcare company GlaxoSmithKline, researchers obtained blood samples from over 5,000 of the approximately 15,000 infants and children who participated in the vaccine's phase 3 trial across 11 study sites in Africa between 2009 and 2013.

The researchers were sent samples when the first symptomatic cases appeared in those vaccinated, as well as samples from all participants at month 14 and month 20 following vaccination. By sequencing those samples, the team determined that, while RTS,S provided at least partial protection against all strains of the parasite, it was significantly more effective at preventing malaria in children with matched allele parasites than in preventing malaria with mismatched allele parasites. The same effect was not noted in infants.

"Now that we understand that at least in the case of this immune response, that there's an allele-specific aspect to it - a particular parasite strain or type creates a certain immune response in the individual - this finding can color how we approach future vaccine discovery and development," said Wirth.

RTS,S is the first malaria vaccine candidate to complete phase 3 trials. Originally designed by scientists at GlaxoSmithKline (GSK) in 1987, development of the vaccine is now being advanced by a public-private partnership between GSK and PATH Malaria Vaccine Initiative.

The work is published online by the New England Journal of Medicine (NEJM).