Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine.


Neafsey, DE; Juraska, M; Bedford, T; Benkeser, D; Valim, C; Griggs, A; Lievens, M; Abdulla, S; Adjei, S; Agbenyega, T; Agnandji, ST; Aide, P; Anderson, S; Ansong, D; Aponte, JJ; Asante, KP; Bejon, P; Birkett, AJ; Bruls, M; Connolly, KM; D'Alessandro, U; Dobaño, C; Gesase, S; Greenwood, B; Grimsby, J; Tinto, H; Hamel, MJ; Hoffman, I; Kamthunzi, P; Kariuki, S; Kremsner, PG; Leach, A; Lell, B; Lennon, NJ; Lusingu, J; Marsh, K; Martinson, F; Molel, JT; Moss, EL; Njuguna, P; Ockenhouse, CF; Ogutu, BR; Otieno, W; Otieno, L; Otieno, K; Owusu-Agyei, S; Park, DJ; Pellé, K; Robbins, D; Russ, C; Ryan, EM; Sacarlal, J; Sogoloff, B; Sorgho, H; Tanner, M; Theander, T; Valea, I; Volkman, SK; Yu, Q; Lapierre, D; Birren, BW; Gilbert, PB; Wirth, DF; (2015) Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine. The New England journal of medicine, 373 (21). pp. 2025-37. ISSN 0028-4793 DOI: 10.1056/NEJMoa1505819

[img]
Preview
Text - Published Version
License: Copyright the publishers

Download (1120Kb) | Preview

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.<br/> 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.<br/> 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.<br/> 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.).<br/>

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Disease Control
Research Centre: Malaria Centre
Vaccine Centre
PubMed ID: 26488565
Web of Science ID: 364957700008
URI: http://researchonline.lshtm.ac.uk/id/eprint/2331814

Statistics


Download activity - last 12 months
Downloads since deposit
65Downloads
204Hits
Accesses by country - last 12 months
Accesses by referrer - last 12 months
Impact and interest
Additional statistics for this record are available via IRStats2

Actions (login required)

Edit Item Edit Item