| dc.contributor.author | Daniel E Neafsey, Michal Juraska, Trevor Bedford, David Benkeser, Clarissa Valim, Allison Griggs, Marc Lievens, Salim Abdulla, Samuel Adjei, Tsiri Agbenyega, Selidji T Agnandji, Pedro Aide, Scott Anderson, Daniel Ansong, John J Aponte, Kwaku Poku Asante, Philip Bejon, Ashley J Birkett, Myriam Bruls, Kristen M Connolly, Umberto D’Alessandro, Carlota Dobaño, Samwel Gesase, Brian Greenwood, Jonna Grimsby, Halidou Tinto, Mary J Hamel, Irving Hoffman, Portia Kamthunzi, Simon Kariuki, Peter G Kremsner, Amanda Leach, Bertrand Lell, Niall J Lennon, John Lusingu, Kevin Marsh, Francis Martinson, Jackson T Molel, Eli L Moss, Patricia Njuguna, Christian F Ockenhouse, Bernhards Ragama Ogutu, Walter Otieno, Lucas Otieno, Kephas Otieno, Seth Owusu-Agyei, Daniel J Park, Karell Pellé, Dana Robbins, Carsten Russ, Elizabeth M Ryan, Jahit Sacarlal, Brian Sogoloff, Hermann Sorgho, Marcel Tanner, Thor Theander, Innocent Valea, Sarah K Volkman, Qing Yu, Didier Lapierre, Bruce W Birren, Peter B Gilbert, Dyann F Wirth | |
| dc.description.abstract | BACKGROUND
The RTS,S/AS01 vaccine targets the circumsporozoite protein of Plasmodium falciparum and has partial protective efficacy against clinical and severe malaria disease in infants and children. We investigated whether the vaccine efficacy was
specific to certain parasite genotypes at the circumsporozoite protein locus.
METHODS
We used polymerase chain reaction–based next-generation sequencing of DNA
extracted from samples from 4985 participants to survey circumsporozoite protein
polymorphisms. We evaluated the effect that polymorphic positions and haplotypic regions within the circumsporozoite protein had on vaccine efficacy against
first episodes of clinical malaria within 1 year after vaccination.
RESULTS
In the per-protocol group of 4577 RTS,S/AS01-vaccinated participants and 2335
control-vaccinated participants who were 5 to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% (95% confidence interval [CI], 34.6 to 62.3)
against clinical malaria in which parasites matched the vaccine in the entire circumsporozoite protein C-terminal (139 infections), as compared with 33.4% (95%
CI, 29.3 to 37.2) against mismatched malaria (1951 infections) (P=0.04 for differential vaccine efficacy). The vaccine efficacy based on the hazard ratio was 62.7%
(95% CI, 51.6 to 71.3) against matched infections versus 54.2% (95% CI, 49.9 to 58.1)
against mismatched infections (P=0.06). In the group of infants 6 to 12 weeks of age,
there was no evidence of differential allele-specific vaccine efficacy.
CONCLUSIONS
These results suggest that among children 5 to 17 months of age, the RTS,S vaccine has greater activity against malaria parasites with the matched circumsporozoite protein allele than against mismatched malaria. The overall vaccine efficacy
in this age category will depend on the proportion of matched alleles in the local
parasite population; in this trial, less than 10% of parasites had matched alleles.
(Funded by the National Institutes of Health and others.) | en_US |
