Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age

Philip Bejon; John Lusingu; Ally Olotu; Amanda Leach; Marc Lievens; Johan Vekemans; Salum Mshamu; Trudie Lang; Jayne Gould; Marie-Claude Dubois; Marie-Ange Demoitié; Jean-Francois Stallaert; Preeti Vansadia; Terrell Carter; Patricia Njuguna; Ken O Awuondo; Anangisye Malabeja; Omar Abdul; Samwel Gesase; Neema Mturi; Chris J Drakeley; Barbara Savarese; Tonya Villafana; W Ripley Ballou; Joe Cohen; Eleanor M Riley; Martha M Lemnge; Kevin Marsh; Lorenz von Seidlein

doi:10.1056/NEJMoa0807381

Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age

Philip Bejon, John Lusingu, Ally Olotu, Amanda Leach, Marc Lievens, Johan Vekemans, Salum Mshamu, Trudie Lang, Jayne Gould, Marie-Claude Dubois, Marie-Ange Demoitié, Jean-Francois Stallaert, Preeti Vansadia, Terrell Carter, Patricia Njuguna, Ken O Awuondo, Anangisye Malabeja, Omar Abdul, Samwel Gesase, Neema MturiChris J Drakeley, Barbara Savarese, Tonya Villafana, W Ripley Ballou, Joe Cohen, Eleanor M Riley, Martha M Lemnge, Kevin Marsh, Lorenz von Seidlein

321 Citations (Scopus)

Abstract

BACKGROUND: Plasmodium falciparum malaria is a pressing global health problem. A previous study of the malaria vaccine RTS,S (which targets the circumsporozoite protein), given with an adjuvant system (AS02A), showed a 30% rate of protection against clinical malaria in children 1 to 4 years of age. We evaluated the efficacy of RTS,S given with a more immunogenic adjuvant system (AS01E) in children 5 to 17 months of age, a target population for vaccine licensure. METHODS: We conducted a double-blind, randomized trial of RTS,S/AS01E vaccine as compared with rabies vaccine in children in Kilifi, Kenya, and Korogwe, Tanzania. The primary end point was fever with a falciparum parasitemia density of more than 2500 parasites per microliter, and the mean duration of follow-up was 7.9 months (range, 4.5 to 10.5). RESULTS: A total of 894 children were randomly assigned to receive the RTS,S/AS01E vaccine or the control (rabies) vaccine. Among the 809 children who completed the study procedures according to the protocol, the cumulative number in whom clinical malaria developed was 32 of 402 assigned to receive RTS,S/AS01E and 66 of 407 assigned to receive the rabies vaccine; the adjusted efficacy rate for RTS,S/AS01E was 53% (95% confidence interval [CI], 28 to 69; P<0.001) on the basis of Cox regression. Overall, there were 38 episodes of clinical malaria among recipients of RTS,S/AS01E, as compared with 86 episodes among recipients of the rabies vaccine, with an adjusted rate of efficacy against all malarial episodes of 56% (95% CI, 31 to 72; P<0.001). All 894 children were included in the intention-to-treat analysis, which showed an unadjusted efficacy rate of 49% (95% CI, 26 to 65; P<0.001). There were fewer serious adverse events among recipients of RTS,S/AS01E, and this reduction was not only due to a difference in the number of admissions directly attributable to malaria. CONCLUSIONS: RTS,S/AS01E shows promise as a candidate malaria vaccine. (ClinicalTrials.gov number, NCT00380393.)

Original language	English
Journal	New England Journal of Medicine
Volume	359
Issue number	24
Pages (from-to)	2521-32
Number of pages	11
ISSN	0028-4793
DOIs	https://doi.org/10.1056/NEJMoa0807381
Publication status	Published - 2008

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10.1056/NEJMoa0807381

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Bejon, P., Lusingu, J., Olotu, A., Leach, A., Lievens, M., Vekemans, J., Mshamu, S., Lang, T., Gould, J., Dubois, M-C., Demoitié, M-A., Stallaert, J-F., Vansadia, P., Carter, T., Njuguna, P., Awuondo, K. O., Malabeja, A., Abdul, O., Gesase, S., ... von Seidlein, L. (2008). Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age. New England Journal of Medicine, 359(24), 2521-32. https://doi.org/10.1056/NEJMoa0807381

Bejon, P, Lusingu, J, Olotu, A, Leach, A, Lievens, M, Vekemans, J, Mshamu, S, Lang, T, Gould, J, Dubois, M-C, Demoitié, M-A, Stallaert, J-F, Vansadia, P, Carter, T, Njuguna, P, Awuondo, KO, Malabeja, A, Abdul, O, Gesase, S, Mturi, N, Drakeley, CJ, Savarese, B, Villafana, T, Ballou, WR, Cohen, J, Riley, EM, Lemnge, MM, Marsh, K & von Seidlein, L 2008, 'Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age', New England Journal of Medicine, vol. 359, no. 24, pp. 2521-32. https://doi.org/10.1056/NEJMoa0807381

@article{1d338920041311deb05e000ea68e967b,

title = "Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age",

abstract = "BACKGROUND: Plasmodium falciparum malaria is a pressing global health problem. A previous study of the malaria vaccine RTS,S (which targets the circumsporozoite protein), given with an adjuvant system (AS02A), showed a 30% rate of protection against clinical malaria in children 1 to 4 years of age. We evaluated the efficacy of RTS,S given with a more immunogenic adjuvant system (AS01E) in children 5 to 17 months of age, a target population for vaccine licensure. METHODS: We conducted a double-blind, randomized trial of RTS,S/AS01E vaccine as compared with rabies vaccine in children in Kilifi, Kenya, and Korogwe, Tanzania. The primary end point was fever with a falciparum parasitemia density of more than 2500 parasites per microliter, and the mean duration of follow-up was 7.9 months (range, 4.5 to 10.5). RESULTS: A total of 894 children were randomly assigned to receive the RTS,S/AS01E vaccine or the control (rabies) vaccine. Among the 809 children who completed the study procedures according to the protocol, the cumulative number in whom clinical malaria developed was 32 of 402 assigned to receive RTS,S/AS01E and 66 of 407 assigned to receive the rabies vaccine; the adjusted efficacy rate for RTS,S/AS01E was 53% (95% confidence interval [CI], 28 to 69; P<0.001) on the basis of Cox regression. Overall, there were 38 episodes of clinical malaria among recipients of RTS,S/AS01E, as compared with 86 episodes among recipients of the rabies vaccine, with an adjusted rate of efficacy against all malarial episodes of 56% (95% CI, 31 to 72; P<0.001). All 894 children were included in the intention-to-treat analysis, which showed an unadjusted efficacy rate of 49% (95% CI, 26 to 65; P<0.001). There were fewer serious adverse events among recipients of RTS,S/AS01E, and this reduction was not only due to a difference in the number of admissions directly attributable to malaria. CONCLUSIONS: RTS,S/AS01E shows promise as a candidate malaria vaccine. (ClinicalTrials.gov number, NCT00380393.)",

author = "Philip Bejon and John Lusingu and Ally Olotu and Amanda Leach and Marc Lievens and Johan Vekemans and Salum Mshamu and Trudie Lang and Jayne Gould and Marie-Claude Dubois and Marie-Ange Demoiti{\'e} and Jean-Francois Stallaert and Preeti Vansadia and Terrell Carter and Patricia Njuguna and Awuondo, {Ken O} and Anangisye Malabeja and Omar Abdul and Samwel Gesase and Neema Mturi and Drakeley, {Chris J} and Barbara Savarese and Tonya Villafana and Ballou, {W Ripley} and Joe Cohen and Riley, {Eleanor M} and Lemnge, {Martha M} and Kevin Marsh and {von Seidlein}, Lorenz",

note = "Keywords: Animals; Antibodies, Protozoan; Double-Blind Method; Female; Humans; Infant; Kaplan-Meiers Estimate; Malaria Vaccines; Malaria, Falciparum; Male; Plasmodium falciparum; Proportional Hazards Models; Protozoan Proteins",

year = "2008",

doi = "10.1056/NEJMoa0807381",

language = "English",

volume = "359",

pages = "2521--32",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachusetts Medical Society",

number = "24",

}

TY - JOUR

T1 - Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age

AU - Bejon, Philip

AU - Lusingu, John

AU - Olotu, Ally

AU - Leach, Amanda

AU - Lievens, Marc

AU - Vekemans, Johan

AU - Mshamu, Salum

AU - Lang, Trudie

AU - Gould, Jayne

AU - Dubois, Marie-Claude

AU - Demoitié, Marie-Ange

AU - Stallaert, Jean-Francois

AU - Vansadia, Preeti

AU - Carter, Terrell

AU - Njuguna, Patricia

AU - Awuondo, Ken O

AU - Malabeja, Anangisye

AU - Abdul, Omar

AU - Gesase, Samwel

AU - Mturi, Neema

AU - Drakeley, Chris J

AU - Savarese, Barbara

AU - Villafana, Tonya

AU - Ballou, W Ripley

AU - Cohen, Joe

AU - Riley, Eleanor M

AU - Lemnge, Martha M

AU - Marsh, Kevin

AU - von Seidlein, Lorenz

N1 - Keywords: Animals; Antibodies, Protozoan; Double-Blind Method; Female; Humans; Infant; Kaplan-Meiers Estimate; Malaria Vaccines; Malaria, Falciparum; Male; Plasmodium falciparum; Proportional Hazards Models; Protozoan Proteins

PY - 2008

Y1 - 2008

N2 - BACKGROUND: Plasmodium falciparum malaria is a pressing global health problem. A previous study of the malaria vaccine RTS,S (which targets the circumsporozoite protein), given with an adjuvant system (AS02A), showed a 30% rate of protection against clinical malaria in children 1 to 4 years of age. We evaluated the efficacy of RTS,S given with a more immunogenic adjuvant system (AS01E) in children 5 to 17 months of age, a target population for vaccine licensure. METHODS: We conducted a double-blind, randomized trial of RTS,S/AS01E vaccine as compared with rabies vaccine in children in Kilifi, Kenya, and Korogwe, Tanzania. The primary end point was fever with a falciparum parasitemia density of more than 2500 parasites per microliter, and the mean duration of follow-up was 7.9 months (range, 4.5 to 10.5). RESULTS: A total of 894 children were randomly assigned to receive the RTS,S/AS01E vaccine or the control (rabies) vaccine. Among the 809 children who completed the study procedures according to the protocol, the cumulative number in whom clinical malaria developed was 32 of 402 assigned to receive RTS,S/AS01E and 66 of 407 assigned to receive the rabies vaccine; the adjusted efficacy rate for RTS,S/AS01E was 53% (95% confidence interval [CI], 28 to 69; P<0.001) on the basis of Cox regression. Overall, there were 38 episodes of clinical malaria among recipients of RTS,S/AS01E, as compared with 86 episodes among recipients of the rabies vaccine, with an adjusted rate of efficacy against all malarial episodes of 56% (95% CI, 31 to 72; P<0.001). All 894 children were included in the intention-to-treat analysis, which showed an unadjusted efficacy rate of 49% (95% CI, 26 to 65; P<0.001). There were fewer serious adverse events among recipients of RTS,S/AS01E, and this reduction was not only due to a difference in the number of admissions directly attributable to malaria. CONCLUSIONS: RTS,S/AS01E shows promise as a candidate malaria vaccine. (ClinicalTrials.gov number, NCT00380393.)

AB - BACKGROUND: Plasmodium falciparum malaria is a pressing global health problem. A previous study of the malaria vaccine RTS,S (which targets the circumsporozoite protein), given with an adjuvant system (AS02A), showed a 30% rate of protection against clinical malaria in children 1 to 4 years of age. We evaluated the efficacy of RTS,S given with a more immunogenic adjuvant system (AS01E) in children 5 to 17 months of age, a target population for vaccine licensure. METHODS: We conducted a double-blind, randomized trial of RTS,S/AS01E vaccine as compared with rabies vaccine in children in Kilifi, Kenya, and Korogwe, Tanzania. The primary end point was fever with a falciparum parasitemia density of more than 2500 parasites per microliter, and the mean duration of follow-up was 7.9 months (range, 4.5 to 10.5). RESULTS: A total of 894 children were randomly assigned to receive the RTS,S/AS01E vaccine or the control (rabies) vaccine. Among the 809 children who completed the study procedures according to the protocol, the cumulative number in whom clinical malaria developed was 32 of 402 assigned to receive RTS,S/AS01E and 66 of 407 assigned to receive the rabies vaccine; the adjusted efficacy rate for RTS,S/AS01E was 53% (95% confidence interval [CI], 28 to 69; P<0.001) on the basis of Cox regression. Overall, there were 38 episodes of clinical malaria among recipients of RTS,S/AS01E, as compared with 86 episodes among recipients of the rabies vaccine, with an adjusted rate of efficacy against all malarial episodes of 56% (95% CI, 31 to 72; P<0.001). All 894 children were included in the intention-to-treat analysis, which showed an unadjusted efficacy rate of 49% (95% CI, 26 to 65; P<0.001). There were fewer serious adverse events among recipients of RTS,S/AS01E, and this reduction was not only due to a difference in the number of admissions directly attributable to malaria. CONCLUSIONS: RTS,S/AS01E shows promise as a candidate malaria vaccine. (ClinicalTrials.gov number, NCT00380393.)

U2 - 10.1056/NEJMoa0807381

DO - 10.1056/NEJMoa0807381

M3 - Journal article

C2 - 19064627

SN - 0028-4793

VL - 359

SP - 2521

EP - 2532

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 24

ER -

Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age

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