Genetic variability in the surface protein targeted by an experimental malaria vaccine explains why the vaccine provided only moderate protection among children during clinical testing, a new study reveals.
The research, published online in the New England Journal of Medicine (2015 Oct 21. doi: 10.1056/NEJMoa1505819), was intended to determine whether the efficacy of the malaria vaccine candidate RTS,S/AS01 (RTS,S) was specific to certain parasite genotypes at the circumsporozoite (CS) protein locus. The researchers, led by Daniel Neafsey, Ph.D., associate director of the Genomic Center for Infectious Diseases at the Broad Institute of MIT in Boston, used polymerase chain reaction–based next-generation sequencing of DNA to evaluate blood samples from nearly 5,000 infants and children who participated in Phase III clinical testing of the vaccine. They found that the RTS,S vaccine was most effective at preventing malaria in children aged 5-17 months who were infected with parasites with the same protein variant that the RTS,S vaccine targeted, while a mismatch corresponded with a lesser degree of protection.
The RTS,S vaccine was designed to target the CS protein found on the surface of malaria-causing Plasmodium parasites. However, while the CS protein is genetically diverse, the RTS,S vaccine incorporates only one variant. Previous studies examining genetic variations in the CS protein did not suggest that the variations may limit or restrict vaccine protection.
“The overall vaccine efficacy in this age category will depend on the proportion of matched alleles in the local parasite population,” Dr. Neafsey and his coauthors wrote. “In this trial, less than 10% of parasites had matched alleles.”
The authors reported no relevant disclosures.
To read the entire study, click here.
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