Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine
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Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine. / Neafsey, Daniel E; Juraska, Michal; Bedford, Trevor; Benkeser, David; Valim, Clarissa; Griggs, Allison; Lievens, Marc; Abdulla, Salim; Adjei, Samuel; Agbenyega, Tsiri; Agnandji, Selidji T; Aide, Pedro; Anderson, Scott; Ansong, Daniel; Aponte, John J; Asante, Kwaku Poku; Bejon, Philip; Birkett, Ashley J; Bruls, Myriam; Connolly, Kristen M; D'Alessandro, Umberto; Dobaño, Carlota; Gesase, Samwel; Greenwood, Brian; Grimsby, Jonna; Tinto, Halidou; Hamel, Mary J; Hoffman, Irving; Kamthunzi, Portia; Kariuki, Simon; Kremsner, Peter G; Leach, Amanda; Lell, Bertrand; Lennon, Niall J; Lusingu, John; Marsh, Kevin; Martinson, Francis; Molel, Jackson T; Moss, Eli L; Njuguna, Patricia; Ockenhouse, Christian F; Ogutu, Bernhards Ragama; Otieno, Walter; Otieno, Lucas; Otieno, Kephas; Owusu-Agyei, Seth; Park, Daniel J; Pellé, Karell; Robbins, Dana; Russ, Carsten; Ryan, Elizabeth M; Sacarlal, Jahit; Sogoloff, Brian; Sorgho, Hermann; Tanner, Marcel; Theander, Thor; Valea, Innocent; Volkman, Sarah K; Yu, Qing; Lapierre, Didier; Birren, Bruce W; Gilbert, Peter B; Wirth, Dyann F.
In: New England Journal of Medicine, Vol. 373, No. 21, 2015, p. 2025-37.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine
AU - Neafsey, Daniel E
AU - Juraska, Michal
AU - Bedford, Trevor
AU - Benkeser, David
AU - Valim, Clarissa
AU - Griggs, Allison
AU - Lievens, Marc
AU - Abdulla, Salim
AU - Adjei, Samuel
AU - Agbenyega, Tsiri
AU - Agnandji, Selidji T
AU - Aide, Pedro
AU - Anderson, Scott
AU - Ansong, Daniel
AU - Aponte, John J
AU - Asante, Kwaku Poku
AU - Bejon, Philip
AU - Birkett, Ashley J
AU - Bruls, Myriam
AU - Connolly, Kristen M
AU - D'Alessandro, Umberto
AU - Dobaño, Carlota
AU - Gesase, Samwel
AU - Greenwood, Brian
AU - Grimsby, Jonna
AU - Tinto, Halidou
AU - Hamel, Mary J
AU - Hoffman, Irving
AU - Kamthunzi, Portia
AU - Kariuki, Simon
AU - Kremsner, Peter G
AU - Leach, Amanda
AU - Lell, Bertrand
AU - Lennon, Niall J
AU - Lusingu, John
AU - Marsh, Kevin
AU - Martinson, Francis
AU - Molel, Jackson T
AU - Moss, Eli L
AU - Njuguna, Patricia
AU - Ockenhouse, Christian F
AU - Ogutu, Bernhards Ragama
AU - Otieno, Walter
AU - Otieno, Lucas
AU - Otieno, Kephas
AU - Owusu-Agyei, Seth
AU - Park, Daniel J
AU - Pellé, Karell
AU - Robbins, Dana
AU - Russ, Carsten
AU - Ryan, Elizabeth M
AU - Sacarlal, Jahit
AU - Sogoloff, Brian
AU - Sorgho, Hermann
AU - Tanner, Marcel
AU - Theander, Thor
AU - Valea, Innocent
AU - Volkman, Sarah K
AU - Yu, Qing
AU - Lapierre, Didier
AU - Birren, Bruce W
AU - Gilbert, Peter B
AU - Wirth, Dyann F
PY - 2015
Y1 - 2015
N2 - 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.).
AB - 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.).
U2 - 10.1056/NEJMoa1505819
DO - 10.1056/NEJMoa1505819
M3 - Journal article
C2 - 26488565
VL - 373
SP - 2025
EP - 2037
JO - New England Journal of Medicine
JF - New England Journal of Medicine
SN - 0028-4793
IS - 21
ER -
ID: 148436163