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

Eusebio V Macete¹^,2^,3 , Jahit Sacarlal¹^,4 , John J Aponte¹^,2 , Amanda Leach⁶ , Margarita M Navia¹^,2 , Jessica Milman⁷ , Caterina Guinovart¹^,2 , Inacio Mandomando¹^,5 , Yolanda López-Púa² , Marc Lievens⁶ , Alex Owusu-Ofori⁶ , Marie-Claude Dubois⁶ , Conor P Cahill⁶ , Marguerite Koutsoukos⁶ , Marla Sillman⁷ , Ricardo Thompson¹^,4^,5 , Filip Dubovsky⁷ , W Ripley Ballou⁶ , Joe Cohen⁶ and Pedro L Alonso¹^,2

¹Centro de Investigação em Saúde de Manhiça (CISM), Manhiça, Mozambique

²Centro de Salud Internacional, Hospital Clínic/Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain

³Direcção Nacional de Saúde, Ministerio de Saúde, Maputo, Mozambique

⁴Faculdade de Medicina, Universidade Eduardo Mondlane, Maputo, Mozambique

⁵Instituto Nacional de Saúde, Ministerio de Saúde, Maputo, Mozambique

⁶GlaxoSmithKline Biologicals, Rixensart, Belgium

⁷PATH Malaria Vaccine Initiative (MVI), Bethesda, MD, USA

author email corresponding author email

Trials 2007, 8:11doi:10.1186/1745-6215-8-11


Published:	26 March 2007

Abstract

Background

Previous 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.

Methods

We 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.

Results

Both 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).

Conclusion

Our 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.