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Clinical Trial
. 2009 Oct 27;4(10):e7611.
doi: 10.1371/journal.pone.0007611.

A randomized trial assessing the safety and immunogenicity of AS01 and AS02 adjuvanted RTS,S malaria vaccine candidates in children in Gabon

Bertrand Lell  1 , Selidji Agnandji, Isabelle von Glasenapp, Sonja Haertle, Sunny Oyakhiromen, Saadou Issifou, Johan Vekemans, Amanda Leach, Marc Lievens, Marie-Claude Dubois, Marie-Ange Demoitie, Terrell Carter, Tonya Villafana, W Ripley Ballou, Joe Cohen, Peter G Kremsner
Affiliations
Clinical Trial

A randomized trial assessing the safety and immunogenicity of AS01 and AS02 adjuvanted RTS,S malaria vaccine candidates in children in Gabon

Bertrand Lell et al. PLoS One. .

Abstract

Background: The malaria vaccine candidate antigen RTS,S includes parts of the pre-erythrocytic stage circumsporozoite protein fused to the Hepatitis B surface antigen. Two Adjuvant Systems are in development for this vaccine, an oil-in water emulsion--based formulation (AS02) and a formulation based on liposomes (AS01).

Methods & principal findings: In this Phase II, double-blind study (NCT00307021), 180 healthy Gabonese children aged 18 months to 4 years were randomized to receive either RTS,S/AS01(E) or RTS,S/AS02(D), on a 0-1-2 month vaccination schedule. The children were followed-up daily for six days after each vaccination and monthly for 14 months. Blood samples were collected at 4 time-points. Both vaccines were well tolerated. Safety parameters were distributed similarly between the two groups. Both vaccines elicited a strong specific immune response after Doses 2 and 3 with a ratio of anti-CS GMT titers (AS02(D)/AS01(E)) of 0.88 (95% CI: 0.68-1.15) post-Dose 3. After Doses 2 and 3 of experimental vaccines, anti-CS and anti-HBs antibody GMTs were higher in children who had been previously vaccinated with at least one dose of hepatitis B vaccine compared to those not previously vaccinated.

Conclusions: RTS,S/AS01(E) proved similarly as well tolerated and immunogenic as RTS,S/AS02(D), completing an essential step in the age de-escalation process within the RTS,S clinical development plan.

Trial registration: ClinicalTrials.gov. NCT00307021.

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Conflict of interest statement

Competing Interests: M.A.D., M-C.D., A.L., M.L., J.V., J.C. are employees of GSK Biologicals. A.L., J.C. and M.C.D. own shares in GSK. W.R.B. was an employee of GSK Biologicals during study design and implementation, but became an employee of the Gates Foundation by the time results were available. J.C. and W.R.B. are listed as inventors of patented malaria vaccines, however, neither individual holds a patent for a malaria vaccine. There are no conflicts of interest for other authors.

Figures

Figure 1
Figure 1. Subject disposition.
Figure 2
Figure 2. The effect of previous hepatitis B vaccination on anti-CS antibodies.
Boxplot graph of anti-CS responses. Represents Q25, median, Q75, highest and lowest observation below/above 1.5 times interquartile range and individual data points below/above 1.5 times interquartile range. GMTs are indicated by +.
Figure 3
Figure 3. The effect of previous hepatitis B vaccination on anti-HBs antibodies.
Boxplot graph of anti-HBs responses. Represents Q25, median, Q75, highest and lowest observation below/above 1.5 times interquartile range and individual data points below/above 1.5 times interquartile range. GMTs are indicated by +.
See this image and copyright information in PMC

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