Safety of the malaria vaccine candidate, RTS,S/AS01E in 5 to 17 month old Kenyan and Tanzanian Children

John Lusingu; Ally Olotu; Amanda Leach; Marc Lievens; Johan Vekemans; Aurélie Olivier; Sarah Benns; Raimos Olomi; Salum Msham; Trudie Lang; Jayne Gould; Karin Hallez; Yolanda Guerra; Patricia Njuguna; Ken O Awuondo; Anangisye Malabeja; Omar Abdul; Samwel Gesase; Denise Dekker; Lincoln Malle; Sadiki Ismael; Neema Mturi; Chris J Drakeley; Barbara Savarese; Tonya Villafana; W Ripley Ballou; Joe Cohen; Eleanor M Riley; Martha M Lemnge; Kevin Marsh; Philip Bejon; Lorenz von Seidlein

doi:10.1371/journal.pone.0014090

Safety of the malaria vaccine candidate, RTS,S/AS01E in 5 to 17 month old Kenyan and Tanzanian Children

John Lusingu, Ally Olotu, Amanda Leach, Marc Lievens, Johan Vekemans, Aurélie Olivier, Sarah Benns, Raimos Olomi, Salum Msham, Trudie Lang, Jayne Gould, Karin Hallez, Yolanda Guerra, Patricia Njuguna, Ken O Awuondo, Anangisye Malabeja, Omar Abdul, Samwel Gesase, Denise Dekker, Lincoln MalleSadiki Ismael, Neema Mturi, Chris J Drakeley, Barbara Savarese, Tonya Villafana, W Ripley Ballou, Joe Cohen, Eleanor M Riley, Martha M Lemnge, Kevin Marsh, Philip Bejon, Lorenz von Seidlein

Centre for Medical Parasitology

17 Citationer (Scopus)

Abstract

The malaria vaccine candidate, RTS,S/AS01(E), showed promising protective efficacy in a trial of Kenyan and Tanzanian children aged 5 to 17 months. Here we report on the vaccine's safety and tolerability. The experimental design was a Phase 2b, two-centre, double-blind (observer- and participant-blind), randomised (1:1 ratio) controlled trial. Three doses of study or control (rabies) vaccines were administered intramuscularly at 1 month intervals. Solicited adverse events (AEs) were collected for 7 days after each vaccination. There was surveillance and reporting for unsolicited adverse events for 30 days after each vaccination. Serious adverse events (SAEs) were recorded throughout the study period which lasted for 14 months after dose 1 in Korogwe, Tanzania and an average of 18 months post-dose 1 in Kilifi, Kenya. Blood samples for safety monitoring of haematological, renal and hepatic functions were taken at baseline, 3, 10 and 14 months after dose 1. A total of 894 children received RTS,S/AS01(E) or rabies vaccine between March and August 2007. Overall, children vaccinated with RTS,S/AS01(E) had fewer SAEs (51/447) than children in the control group (88/447). One SAE episode in a RTS,S/AS01(E) recipient and nine episodes among eight rabies vaccine recipients met the criteria for severe malaria. Unsolicited AEs were reported in 78% of subjects in the RTS,S/AS01(E) group and 74% of subjects in the rabies vaccine group. In both vaccine groups, gastroenteritis and pneumonia were the most frequently reported unsolicited AE. Fever was the most frequently observed solicited AE and was recorded after 11% of RTS,S/AS01(E) doses compared to 31% of doses of rabies vaccine. The candidate vaccine RTS,S/AS01(E) showed an acceptable safety profile in children living in a malaria-endemic area in East Africa. More data on the safety of RTS,S/AS01(E) will become available from the Phase 3 programme.

Originalsprog	Engelsk
Tidsskrift	P L o S One
Vol/bind	5
Udgave nummer	11
Sider (fra-til)	e14090
ISSN	1932-6203
DOI	https://doi.org/10.1371/journal.pone.0014090
Status	Udgivet - 1 jan. 2010

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Lusingu, J., Olotu, A., Leach, A., Lievens, M., Vekemans, J., Olivier, A., Benns, S., Olomi, R., Msham, S., Lang, T., Gould, J., Hallez, K., Guerra, Y., Njuguna, P., Awuondo, K. O., Malabeja, A., Abdul, O., Gesase, S., Dekker, D., ... von Seidlein, L. (2010). Safety of the malaria vaccine candidate, RTS,S/AS01E in 5 to 17 month old Kenyan and Tanzanian Children. P L o S One, 5(11), e14090. https://doi.org/10.1371/journal.pone.0014090

Lusingu, J, Olotu, A, Leach, A, Lievens, M, Vekemans, J, Olivier, A, Benns, S, Olomi, R, Msham, S, Lang, T, Gould, J, Hallez, K, Guerra, Y, Njuguna, P, Awuondo, KO, Malabeja, A, Abdul, O, Gesase, S, Dekker, D, Malle, L, Ismael, S, Mturi, N, Drakeley, CJ, Savarese, B, Villafana, T, Ballou, WR, Cohen, J, Riley, EM, Lemnge, MM, Marsh, K, Bejon, P & von Seidlein, L 2010, 'Safety of the malaria vaccine candidate, RTS,S/AS01E in 5 to 17 month old Kenyan and Tanzanian Children', P L o S One, bind 5, nr. 11, s. e14090. https://doi.org/10.1371/journal.pone.0014090

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title = "Safety of the malaria vaccine candidate, RTS,S/AS01E in 5 to 17 month old Kenyan and Tanzanian Children",

abstract = "The malaria vaccine candidate, RTS,S/AS01(E), showed promising protective efficacy in a trial of Kenyan and Tanzanian children aged 5 to 17 months. Here we report on the vaccine's safety and tolerability. The experimental design was a Phase 2b, two-centre, double-blind (observer- and participant-blind), randomised (1:1 ratio) controlled trial. Three doses of study or control (rabies) vaccines were administered intramuscularly at 1 month intervals. Solicited adverse events (AEs) were collected for 7 days after each vaccination. There was surveillance and reporting for unsolicited adverse events for 30 days after each vaccination. Serious adverse events (SAEs) were recorded throughout the study period which lasted for 14 months after dose 1 in Korogwe, Tanzania and an average of 18 months post-dose 1 in Kilifi, Kenya. Blood samples for safety monitoring of haematological, renal and hepatic functions were taken at baseline, 3, 10 and 14 months after dose 1. A total of 894 children received RTS,S/AS01(E) or rabies vaccine between March and August 2007. Overall, children vaccinated with RTS,S/AS01(E) had fewer SAEs (51/447) than children in the control group (88/447). One SAE episode in a RTS,S/AS01(E) recipient and nine episodes among eight rabies vaccine recipients met the criteria for severe malaria. Unsolicited AEs were reported in 78% of subjects in the RTS,S/AS01(E) group and 74% of subjects in the rabies vaccine group. In both vaccine groups, gastroenteritis and pneumonia were the most frequently reported unsolicited AE. Fever was the most frequently observed solicited AE and was recorded after 11% of RTS,S/AS01(E) doses compared to 31% of doses of rabies vaccine. The candidate vaccine RTS,S/AS01(E) showed an acceptable safety profile in children living in a malaria-endemic area in East Africa. More data on the safety of RTS,S/AS01(E) will become available from the Phase 3 programme.",

keywords = "Alanine Transaminase, Creatinine, Double-Blind Method, Fever, Gastroenteritis, Humans, Infant, Kenya, Malaria Vaccines, Malaria, Falciparum, Pain, Plasmodium falciparum, Pneumonia, Rabies Vaccines, Sleep Stages, Tanzania, Vaccination",

author = "John Lusingu and Ally Olotu and Amanda Leach and Marc Lievens and Johan Vekemans and Aur{\'e}lie Olivier and Sarah Benns and Raimos Olomi and Salum Msham and Trudie Lang and Jayne Gould and Karin Hallez and Yolanda Guerra and Patricia Njuguna and Awuondo, {Ken O} and Anangisye Malabeja and Omar Abdul and Samwel Gesase and Denise Dekker and Lincoln Malle and Sadiki Ismael 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 Philip Bejon and {von Seidlein}, Lorenz",

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T1 - Safety of the malaria vaccine candidate, RTS,S/AS01E in 5 to 17 month old Kenyan and Tanzanian Children

AU - Lusingu, John

AU - Olotu, Ally

AU - Leach, Amanda

AU - Lievens, Marc

AU - Vekemans, Johan

AU - Olivier, Aurélie

AU - Benns, Sarah

AU - Olomi, Raimos

AU - Msham, Salum

AU - Lang, Trudie

AU - Gould, Jayne

AU - Hallez, Karin

AU - Guerra, Yolanda

AU - Njuguna, Patricia

AU - Awuondo, Ken O

AU - Malabeja, Anangisye

AU - Abdul, Omar

AU - Gesase, Samwel

AU - Dekker, Denise

AU - Malle, Lincoln

AU - Ismael, Sadiki

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 - Bejon, Philip

AU - von Seidlein, Lorenz

PY - 2010/1/1

Y1 - 2010/1/1

N2 - The malaria vaccine candidate, RTS,S/AS01(E), showed promising protective efficacy in a trial of Kenyan and Tanzanian children aged 5 to 17 months. Here we report on the vaccine's safety and tolerability. The experimental design was a Phase 2b, two-centre, double-blind (observer- and participant-blind), randomised (1:1 ratio) controlled trial. Three doses of study or control (rabies) vaccines were administered intramuscularly at 1 month intervals. Solicited adverse events (AEs) were collected for 7 days after each vaccination. There was surveillance and reporting for unsolicited adverse events for 30 days after each vaccination. Serious adverse events (SAEs) were recorded throughout the study period which lasted for 14 months after dose 1 in Korogwe, Tanzania and an average of 18 months post-dose 1 in Kilifi, Kenya. Blood samples for safety monitoring of haematological, renal and hepatic functions were taken at baseline, 3, 10 and 14 months after dose 1. A total of 894 children received RTS,S/AS01(E) or rabies vaccine between March and August 2007. Overall, children vaccinated with RTS,S/AS01(E) had fewer SAEs (51/447) than children in the control group (88/447). One SAE episode in a RTS,S/AS01(E) recipient and nine episodes among eight rabies vaccine recipients met the criteria for severe malaria. Unsolicited AEs were reported in 78% of subjects in the RTS,S/AS01(E) group and 74% of subjects in the rabies vaccine group. In both vaccine groups, gastroenteritis and pneumonia were the most frequently reported unsolicited AE. Fever was the most frequently observed solicited AE and was recorded after 11% of RTS,S/AS01(E) doses compared to 31% of doses of rabies vaccine. The candidate vaccine RTS,S/AS01(E) showed an acceptable safety profile in children living in a malaria-endemic area in East Africa. More data on the safety of RTS,S/AS01(E) will become available from the Phase 3 programme.

AB - The malaria vaccine candidate, RTS,S/AS01(E), showed promising protective efficacy in a trial of Kenyan and Tanzanian children aged 5 to 17 months. Here we report on the vaccine's safety and tolerability. The experimental design was a Phase 2b, two-centre, double-blind (observer- and participant-blind), randomised (1:1 ratio) controlled trial. Three doses of study or control (rabies) vaccines were administered intramuscularly at 1 month intervals. Solicited adverse events (AEs) were collected for 7 days after each vaccination. There was surveillance and reporting for unsolicited adverse events for 30 days after each vaccination. Serious adverse events (SAEs) were recorded throughout the study period which lasted for 14 months after dose 1 in Korogwe, Tanzania and an average of 18 months post-dose 1 in Kilifi, Kenya. Blood samples for safety monitoring of haematological, renal and hepatic functions were taken at baseline, 3, 10 and 14 months after dose 1. A total of 894 children received RTS,S/AS01(E) or rabies vaccine between March and August 2007. Overall, children vaccinated with RTS,S/AS01(E) had fewer SAEs (51/447) than children in the control group (88/447). One SAE episode in a RTS,S/AS01(E) recipient and nine episodes among eight rabies vaccine recipients met the criteria for severe malaria. Unsolicited AEs were reported in 78% of subjects in the RTS,S/AS01(E) group and 74% of subjects in the rabies vaccine group. In both vaccine groups, gastroenteritis and pneumonia were the most frequently reported unsolicited AE. Fever was the most frequently observed solicited AE and was recorded after 11% of RTS,S/AS01(E) doses compared to 31% of doses of rabies vaccine. The candidate vaccine RTS,S/AS01(E) showed an acceptable safety profile in children living in a malaria-endemic area in East Africa. More data on the safety of RTS,S/AS01(E) will become available from the Phase 3 programme.

KW - Alanine Transaminase

KW - Creatinine

KW - Double-Blind Method

KW - Fever

KW - Gastroenteritis

KW - Humans

KW - Infant

KW - Kenya

KW - Malaria Vaccines

KW - Malaria, Falciparum

KW - Pain

KW - Plasmodium falciparum

KW - Pneumonia

KW - Rabies Vaccines

KW - Sleep Stages

KW - Tanzania

KW - Vaccination

U2 - 10.1371/journal.pone.0014090

DO - 10.1371/journal.pone.0014090

M3 - Journal article

C2 - 21124768

SN - 1932-6203

VL - 5

SP - e14090

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 11

ER -

Safety of the malaria vaccine candidate, RTS,S/AS01E in 5 to 17 month old Kenyan and Tanzanian Children

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