Protective Efficacy of Malaria Vaccine Varies with Parasite Strain

Summary and Comment |
October 29, 2015

Protective Efficacy of Malaria Vaccine Varies with Parasite Strain

  1. Mary E. Wilson, MD

Efficacy was higher against parasites that matched the circumsporozoite protein allele in the vaccine than against mismatched ones.

  1. Mary E. Wilson, MD

The RTS,S/AS01 vaccine is based on genetic sequences derived from a single malaria strain, 3D7, but malaria parasites are genetically diverse. Now, in a partially industry-supported study, investigators have assessed differences in vaccine efficacy according to whether the parasites match the vaccine strain at the circumsporozoite protein C-terminal.

The researchers used samples from RTS,S/AS01-vaccinated participants in a phase III trial conducted at 11 sites across 7 African countries. They extracted parasite DNA from dried blood spots and used polymerase chain reaction amplification and next-generation sequencing to assess whether children with clinical malaria had parasites with circumsporozoite protein identical to or different from the 3D7 vaccine strain.

Among children aged 5 to 17 months, mean vaccine efficacy against first-episode clinical malaria within 1 year after vaccination was 62.7% for matched parasites versus 54.2% for mismatched ones. Among infants aged 6 to 12 weeks, there was no difference in allele-specific efficacy, but overall efficacy was lower. Most infections in both age groups were complex, involving two or more distinct parasite lineages. Overall, >90% of the infections were vaccine-mismatched.


The finding that vaccine efficacy depends on the proportion of matched parasites in the local population has profound implications for vaccine use. As an editorialist and the authors note, wide vaccine deployment could lead to loss of efficacy because of selection pressure from vaccine-induced immunity. The editorialist points to the possibility of a next-generation vaccine that would include additional antigens to offer broader protection against diverse parasites. The authors speculate that the lack of allele-specific vaccine efficacy in the younger group (6–12 weeks) may reflect maternal antibody, interactions with other vaccine responses, or differences between infants and children in the immune response. This study is a reminder of the complexity of malaria immunity and the challenges of developing an effective vaccine.

Editor Disclosures at Time of Publication

  • Disclosures for Mary E. Wilson, MD at time of publication Consultant / Advisory board GeoSentinel Surveillance Network (Special Advisor) Editorial boards UpToDate; Clinical Infectious Diseases; International Health; Infectious Diseases in Clinical Practice; Travel Medicine and Infectious Diseases


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