Evaluation of RTS,S/AS02A and RTS,S/AS01B in Adults in a High Malaria Transmission Area |
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| Authors: | Mark E Polhemus Shon A Remich Bernhards R Ogutu John N Waitumbi Lucas Otieno Stella Apollo James F Cummings Kent E Kester Christian F Ockenhouse Ann Stewart Opokua Ofori-Anyinam Isabelle Ramboer Conor P Cahill Marc Lievens Marie-Claude Dubois Marie-Ange Demoitie Amanda Leach Joe Cohen W Ripley Ballou D Gray Heppner Jr |
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| Institution: | 1. US Army Medical Research Unit-Kenya, Nairobi, Kenya.; 2. Kenya Medical Research Institute, Nairobi, Kenya.; 3. Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.; 4. GlaxoSmithKline Biologicals s.a., Rixensart, Belgium.;Walter and Eliza Hall Institute of Medical Research, Australia |
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| Abstract: | BackgroundThis 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.MethodologyA 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 FindingsBoth 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).ConclusionsBoth 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. Trial RegistrationClinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00197054","term_id":"NCT00197054"}}NCT00197054 |
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