Evaluation of RTS,S/AS02A and RTS,S/AS01B in adults in a high malaria transmission area

Mark Polhemus, Shon Remich, Bernhards Ogutu, John Waitumbi, Lucas Otieno, Stella Apollo, James Cummings, Kent Kester, Christian Ockenhouse, Ann Stewart, Opokua Ofori-Anyinam, Isabelle Ramboer, Conor Cahill, Marc Lievens, Marie-Claude Dubois, Marie Ange Demoitie, Amanda Leach, Joe Cohen, Ripley Ballou, Gray Heppner

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: This study advances the clinical development of the RTS,S/AS01B candidate malaria vaccine to malaria endemic populations. As a primary objective it compares the safety and reactogenicity of RTS,S/AS01B to the more extensively evaluated RTS,S/AS02A vaccine.

Methodology: A Phase IIb, single centre, double-blind, controlled trial of 6 months duration with a subsequent 6 month single-blind follow-up conducted in Kisumu West District, Kenya between August 2005 and August 2006. 255 healthy adults aged 18 to 35 years were randomized (1∶1∶1) to receive 3 doses of RTS,S/AS02A, RTS,S/AS01B or rabies vaccine (Rabipur®; Chiron Behring GmbH) at months 0, 1, 2. The primary objective was the occurrence of severe (grade 3) solicited or unsolicited general (i.e. systemic) adverse events (AEs) during 7 days follow up after each vaccination.

Principal Findings:
Both candidate vaccines had a good safety profile and were well tolerated. One grade 3 systemic AE occurred within 7 days of vaccination (RTS,S/AS01B group). No unsolicited AEs or SAEs were related to vaccine. A marked increase in anti-CS antibody GMTs was observed post Dose 2 of both RTS,S/AS01B (31.6 EU/mL [95% CI: 23.9 to 41.6]) and RTS,S/AS02A (16.7 EU/mL [95% CI: 12.9 to 21.7]). A further increase was observed post Dose 3 in both the RTS,S/AS01B (41.4 EU/mL [95% CI: 31.7 to 54.2]) and RTS,S/AS02A (21.4 EU/mL [95% CI: 16.0 to 28.7]) groups. Anti-CS antibody GMTs were significantly greater with RTS,S/AS01B compared to RTS,S/AS02A at all time points post Dose 2 and Dose 3. Both candidate vaccines produced strong anti-HBs responses. Vaccine efficacy in the RTS,S/AS01B group was 29.5% (95% CI: −15.4 to 56.9, p = 0.164) and in the RTS,S/AS02A group 31.7% (95% CI: −11.6 to 58.2, p = 0.128).

Conclusions: Both candidate malaria vaccines were well tolerated over a 12 month surveillance period. A more favorable immunogenicity profile was observed with RTS,S/AS01B than with RTS,S/AS02A.
Original languageEnglish
Article numbere6465
Pages (from-to)1-12
Number of pages12
JournalPLoS One
Volume4
Issue number7
DOIs
Publication statusPublished - 31 Jul 2009

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malaria
Malaria
Vaccines
vaccines
Malaria Vaccines
dosage
Anti-Idiotypic Antibodies
Vaccination
Rabies Vaccines
Safety
Antibodies
Kenya
vaccination
antibodies
rabies
immune response
Population
duration
monitoring
malaria vaccines

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Polhemus, M., Remich, S., Ogutu, B., Waitumbi, J., Otieno, L., Apollo, S., ... Heppner, G. (2009). Evaluation of RTS,S/AS02A and RTS,S/AS01B in adults in a high malaria transmission area. PLoS One, 4(7), 1-12. [e6465]. https://doi.org/10.1371/journal.pone.0006465
Polhemus, Mark ; Remich, Shon ; Ogutu, Bernhards ; Waitumbi, John ; Otieno, Lucas ; Apollo, Stella ; Cummings, James ; Kester, Kent ; Ockenhouse, Christian ; Stewart, Ann ; Ofori-Anyinam, Opokua ; Ramboer, Isabelle ; Cahill, Conor ; Lievens, Marc ; Dubois, Marie-Claude ; Demoitie, Marie Ange ; Leach, Amanda ; Cohen, Joe ; Ballou, Ripley ; Heppner, Gray. / Evaluation of RTS,S/AS02A and RTS,S/AS01B in adults in a high malaria transmission area. In: PLoS One. 2009 ; Vol. 4, No. 7. pp. 1-12.
@article{da6e15484c754a7bb1546ce6d62e7d6a,
title = "Evaluation of RTS,S/AS02A and RTS,S/AS01B in adults in a high malaria transmission area",
abstract = "Background: This study advances the clinical development of the RTS,S/AS01B candidate malaria vaccine to malaria endemic populations. As a primary objective it compares the safety and reactogenicity of RTS,S/AS01B to the more extensively evaluated RTS,S/AS02A vaccine.Methodology: A Phase IIb, single centre, double-blind, controlled trial of 6 months duration with a subsequent 6 month single-blind follow-up conducted in Kisumu West District, Kenya between August 2005 and August 2006. 255 healthy adults aged 18 to 35 years were randomized (1∶1∶1) to receive 3 doses of RTS,S/AS02A, RTS,S/AS01B or rabies vaccine (Rabipur{\circledR}; Chiron Behring GmbH) at months 0, 1, 2. The primary objective was the occurrence of severe (grade 3) solicited or unsolicited general (i.e. systemic) adverse events (AEs) during 7 days follow up after each vaccination.Principal Findings: Both candidate vaccines had a good safety profile and were well tolerated. One grade 3 systemic AE occurred within 7 days of vaccination (RTS,S/AS01B group). No unsolicited AEs or SAEs were related to vaccine. A marked increase in anti-CS antibody GMTs was observed post Dose 2 of both RTS,S/AS01B (31.6 EU/mL [95{\%} CI: 23.9 to 41.6]) and RTS,S/AS02A (16.7 EU/mL [95{\%} CI: 12.9 to 21.7]). A further increase was observed post Dose 3 in both the RTS,S/AS01B (41.4 EU/mL [95{\%} CI: 31.7 to 54.2]) and RTS,S/AS02A (21.4 EU/mL [95{\%} CI: 16.0 to 28.7]) groups. Anti-CS antibody GMTs were significantly greater with RTS,S/AS01B compared to RTS,S/AS02A at all time points post Dose 2 and Dose 3. Both candidate vaccines produced strong anti-HBs responses. Vaccine efficacy in the RTS,S/AS01B group was 29.5{\%} (95{\%} CI: −15.4 to 56.9, p = 0.164) and in the RTS,S/AS02A group 31.7{\%} (95{\%} CI: −11.6 to 58.2, p = 0.128).Conclusions: Both candidate malaria vaccines were well tolerated over a 12 month surveillance period. A more favorable immunogenicity profile was observed with RTS,S/AS01B than with RTS,S/AS02A.",
author = "Mark Polhemus and Shon Remich and Bernhards Ogutu and John Waitumbi and Lucas Otieno and Stella Apollo and James Cummings and Kent Kester and Christian Ockenhouse and Ann Stewart and Opokua Ofori-Anyinam and Isabelle Ramboer and Conor Cahill and Marc Lievens and Marie-Claude Dubois and Demoitie, {Marie Ange} and Amanda Leach and Joe Cohen and Ripley Ballou and Gray Heppner",
year = "2009",
month = "7",
day = "31",
doi = "10.1371/journal.pone.0006465",
language = "English",
volume = "4",
pages = "1--12",
journal = "PLoS One",
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Polhemus, M, Remich, S, Ogutu, B, Waitumbi, J, Otieno, L, Apollo, S, Cummings, J, Kester, K, Ockenhouse, C, Stewart, A, Ofori-Anyinam, O, Ramboer, I, Cahill, C, Lievens, M, Dubois, M-C, Demoitie, MA, Leach, A, Cohen, J, Ballou, R & Heppner, G 2009, 'Evaluation of RTS,S/AS02A and RTS,S/AS01B in adults in a high malaria transmission area', PLoS One, vol. 4, no. 7, e6465, pp. 1-12. https://doi.org/10.1371/journal.pone.0006465

Evaluation of RTS,S/AS02A and RTS,S/AS01B in adults in a high malaria transmission area. / Polhemus, Mark; Remich, Shon; Ogutu, Bernhards; Waitumbi, John; Otieno, Lucas; Apollo, Stella; Cummings, James; Kester, Kent; Ockenhouse, Christian; Stewart, Ann; Ofori-Anyinam, Opokua; Ramboer, Isabelle; Cahill, Conor; Lievens, Marc; Dubois, Marie-Claude; Demoitie, Marie Ange; Leach, Amanda; Cohen, Joe; Ballou, Ripley; Heppner, Gray.

In: PLoS One, Vol. 4, No. 7, e6465, 31.07.2009, p. 1-12.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Evaluation of RTS,S/AS02A and RTS,S/AS01B in adults in a high malaria transmission area

AU - Polhemus, Mark

AU - Remich, Shon

AU - Ogutu, Bernhards

AU - Waitumbi, John

AU - Otieno, Lucas

AU - Apollo, Stella

AU - Cummings, James

AU - Kester, Kent

AU - Ockenhouse, Christian

AU - Stewart, Ann

AU - Ofori-Anyinam, Opokua

AU - Ramboer, Isabelle

AU - Cahill, Conor

AU - Lievens, Marc

AU - Dubois, Marie-Claude

AU - Demoitie, Marie Ange

AU - Leach, Amanda

AU - Cohen, Joe

AU - Ballou, Ripley

AU - Heppner, Gray

PY - 2009/7/31

Y1 - 2009/7/31

N2 - Background: This study advances the clinical development of the RTS,S/AS01B candidate malaria vaccine to malaria endemic populations. As a primary objective it compares the safety and reactogenicity of RTS,S/AS01B to the more extensively evaluated RTS,S/AS02A vaccine.Methodology: A Phase IIb, single centre, double-blind, controlled trial of 6 months duration with a subsequent 6 month single-blind follow-up conducted in Kisumu West District, Kenya between August 2005 and August 2006. 255 healthy adults aged 18 to 35 years were randomized (1∶1∶1) to receive 3 doses of RTS,S/AS02A, RTS,S/AS01B or rabies vaccine (Rabipur®; Chiron Behring GmbH) at months 0, 1, 2. The primary objective was the occurrence of severe (grade 3) solicited or unsolicited general (i.e. systemic) adverse events (AEs) during 7 days follow up after each vaccination.Principal Findings: Both candidate vaccines had a good safety profile and were well tolerated. One grade 3 systemic AE occurred within 7 days of vaccination (RTS,S/AS01B group). No unsolicited AEs or SAEs were related to vaccine. A marked increase in anti-CS antibody GMTs was observed post Dose 2 of both RTS,S/AS01B (31.6 EU/mL [95% CI: 23.9 to 41.6]) and RTS,S/AS02A (16.7 EU/mL [95% CI: 12.9 to 21.7]). A further increase was observed post Dose 3 in both the RTS,S/AS01B (41.4 EU/mL [95% CI: 31.7 to 54.2]) and RTS,S/AS02A (21.4 EU/mL [95% CI: 16.0 to 28.7]) groups. Anti-CS antibody GMTs were significantly greater with RTS,S/AS01B compared to RTS,S/AS02A at all time points post Dose 2 and Dose 3. Both candidate vaccines produced strong anti-HBs responses. Vaccine efficacy in the RTS,S/AS01B group was 29.5% (95% CI: −15.4 to 56.9, p = 0.164) and in the RTS,S/AS02A group 31.7% (95% CI: −11.6 to 58.2, p = 0.128).Conclusions: Both candidate malaria vaccines were well tolerated over a 12 month surveillance period. A more favorable immunogenicity profile was observed with RTS,S/AS01B than with RTS,S/AS02A.

AB - Background: This study advances the clinical development of the RTS,S/AS01B candidate malaria vaccine to malaria endemic populations. As a primary objective it compares the safety and reactogenicity of RTS,S/AS01B to the more extensively evaluated RTS,S/AS02A vaccine.Methodology: A Phase IIb, single centre, double-blind, controlled trial of 6 months duration with a subsequent 6 month single-blind follow-up conducted in Kisumu West District, Kenya between August 2005 and August 2006. 255 healthy adults aged 18 to 35 years were randomized (1∶1∶1) to receive 3 doses of RTS,S/AS02A, RTS,S/AS01B or rabies vaccine (Rabipur®; Chiron Behring GmbH) at months 0, 1, 2. The primary objective was the occurrence of severe (grade 3) solicited or unsolicited general (i.e. systemic) adverse events (AEs) during 7 days follow up after each vaccination.Principal Findings: Both candidate vaccines had a good safety profile and were well tolerated. One grade 3 systemic AE occurred within 7 days of vaccination (RTS,S/AS01B group). No unsolicited AEs or SAEs were related to vaccine. A marked increase in anti-CS antibody GMTs was observed post Dose 2 of both RTS,S/AS01B (31.6 EU/mL [95% CI: 23.9 to 41.6]) and RTS,S/AS02A (16.7 EU/mL [95% CI: 12.9 to 21.7]). A further increase was observed post Dose 3 in both the RTS,S/AS01B (41.4 EU/mL [95% CI: 31.7 to 54.2]) and RTS,S/AS02A (21.4 EU/mL [95% CI: 16.0 to 28.7]) groups. Anti-CS antibody GMTs were significantly greater with RTS,S/AS01B compared to RTS,S/AS02A at all time points post Dose 2 and Dose 3. Both candidate vaccines produced strong anti-HBs responses. Vaccine efficacy in the RTS,S/AS01B group was 29.5% (95% CI: −15.4 to 56.9, p = 0.164) and in the RTS,S/AS02A group 31.7% (95% CI: −11.6 to 58.2, p = 0.128).Conclusions: Both candidate malaria vaccines were well tolerated over a 12 month surveillance period. A more favorable immunogenicity profile was observed with RTS,S/AS01B than with RTS,S/AS02A.

U2 - 10.1371/journal.pone.0006465

DO - 10.1371/journal.pone.0006465

M3 - Article

VL - 4

SP - 1

EP - 12

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 7

M1 - e6465

ER -

Polhemus M, Remich S, Ogutu B, Waitumbi J, Otieno L, Apollo S et al. Evaluation of RTS,S/AS02A and RTS,S/AS01B in adults in a high malaria transmission area. PLoS One. 2009 Jul 31;4(7):1-12. e6465. https://doi.org/10.1371/journal.pone.0006465