Why promising malaria vaccine partly protected kids

A recent study has explained the mediocre performance of the world's most advanced malaria vaccine candidate, which offers young children partial protection that wanes with time.

Using new, highly sensitive genomic sequencing technology, the international team of researchers found new biological evidence to help explain why the malaria vaccine candidate RTS,S/AS01 (called RTS,S) provided only moderate protection among vaccinated children during clinical testing.

The researchers, funded in part by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, found that genetic variability in the surface protein targeted by the RTS,S vaccine likely played a significant role.

The RTS,S vaccine was designed to target the circumsporozoite (CS) protein found on the surface of malaria-causing Plasmodium parasites. However, while the CS protein is genetically diverse, meaning that it has different variants, the RTS,S vaccine incorporates only one variant.

In an evaluation of blood samples from nearly 5,000 of the infants and children who participated in Phase 3 clinical testing of the vaccine, the researchers found that the RTS,S vaccine was most effective at preventing malaria in children ages 5 to 17 months infected with parasites with the same protein variant as the RTS,S vaccine, while a mismatch corresponded with a lesser degree of protection. This differential effect was not seen in blood samples from vaccinated infants aged 6 to 12 weeks.

The findings will inform future malaria vaccine development, and the genomics approach used could be applied to other infectious diseases with changing vaccine targets, according to the authors.

The study appears online in the New England Journal of Medicine.