Evaluation of two formulations of adjuvanted RTS, S malaria vaccine in children aged 3 to 5 years living in a malaria-endemic region of Mozambique: a Phase I-IIb randomized double-blind bridging trialReportar como inadecuado




Evaluation of two formulations of adjuvanted RTS, S malaria vaccine in children aged 3 to 5 years living in a malaria-endemic region of Mozambique: a Phase I-IIb randomized double-blind bridging trial - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Trials

, 8:11

First Online: 26 March 2007Received: 10 August 2006Accepted: 26 March 2007DOI: 10.1186-1745-6215-8-11

Cite this article as: Macete, E.V., Sacarlal, J., Aponte, J.J. et al. Trials 2007 8: 11. doi:10.1186-1745-6215-8-11

Abstract

BackgroundPrevious trials of the RTS, S malaria candidate vaccine have shown that this vaccine is safe, tolerated and immunogenic. The development plan for this vaccine aims at administering it in the first year of life through the Expanded Program on Immunization EPI. The objective was to evaluate the safety and reactogenicity of RTS, S-AS02D 0.5 ml dose, a pediatric formulation of GlaxoSmithKline Biologicals- current malaria candidate vaccine RTS, S-AS02A 0.25 ml dose. A 0.5 ml dose of AS02D is composed of the same active ingredients in the same quantities as in a 0.25 ml dose of AS02A and has been developed to be easily introduced into routine EPI practices.

MethodsWe performed a phase I-IIb randomized double-blind bridging study in a malaria-endemic region of Mozambique, to compare the safety and immunogenicity of both candidate vaccines with the aim of replacing RTS, S-AS02A with RTS, S-AS02D as the candidate pediatric vaccine. 200 Mozambican children aged 3 to 5 years were randomized 1:1 to receive one of the 2 vaccines according to a 0, 1, 2 month schedule.

ResultsBoth vaccines were safe and had similar reactogenicity profiles. All subjects with paired pre and post-vaccination samples showed a vaccine response with respect to anti-circumsporozoite CS antibodies irrespective of initial anti-CS serostatus. Geometric mean titers GMTs were 191 EU-ml 95% CI 150–242 in recipients of RTS, S-AS02D compared to 180 EU-ml 95% CI 146–221 in recipients of RTS, S-AS02A. For the anti-hepatitis B surface antigen HBsAg, all subjects were seroprotected at day 90, and the GMTs were 23978 mIU-ml 95% CI 17896–32127 in RTS, S-AS02D recipients and 17410 mIU-ml 95% CI 13322–22752 in RTS, S-AS02A recipients. There was a decrease in anti-CS GMTs between months 3 and 14 in both groups 191 vs 22 EU-mL in RTS, S-AS02D group and 180 vs 29 EU-mL in RTS, S-AS02A group.

ConclusionOur data show that the RTS, S-AS02D is safe, well tolerated, and demonstrates non-inferiority defined as upper limit of the 95% confidence interval of the anti-CS GMT ratio of RTS, S-AS02A to RTS, S-AS02D below 3.0 of the antibody responses to circumsporozoite and HBsAg induced by the RTS, S-AS02D as compared to the RTS, S-AS02A.

Electronic supplementary materialThe online version of this article doi:10.1186-1745-6215-8-11 contains supplementary material, which is available to authorized users.

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Autor: Eusebio V Macete - Jahit Sacarlal - John J Aponte - Amanda Leach - Margarita M Navia - Jessica Milman - Caterina Guinova

Fuente: https://link.springer.com/







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