Phase 1 study of a combination AMA1 blood stage malaria vaccine in Malian children

Background: Apical Membrane Antigen-1 (AMA1) is one of the leading blood stage malaria vaccine candidates. AMA1-C1/ AlhydrogelH consists of an equal mixture of recombinant AMA1 from FVO and 3D7 clones of P. falciparum, adsorbed onto AlhydrogelH. A Phase 1 study in semi-immune adults in Mali showed that the vaccine was safe and immunogenic, with higher antibody responses in those who received the 80 mg dose. The aim of this study was to assess the safety and immunogenicity of this vaccine in young children in a malaria endemic area. Design: This was a Phase 1 dose escalating study in 36 healthy children aged 2–3 years started in March 2006 in Donéguébougou, Mali. Eighteen children in the first cohort were randomized 2:1 to receive either 20 mg AMA1-C1/ AlhydrogelH or Haemophilus influenzae type b HiberixH vaccine. Two weeks later 18 children in the second cohort were randomized 2:1 to receive either 80 mg AMA1-C1/AlhydrogelH or Haemophilus influenzae type b HiberixH vaccine. Vaccinations were administered on Days 0 and 28 and participants were examined on Days 1, 2, 3, 7, and 14 after vaccination and then about every two months. Results to Day 154 are reported in this manuscript. Results: Of 36 volunteers enrolled, 33 received both vaccinations. There were 9 adverse events related to the vaccination in subjects who received AMA1-C1 vaccine and 7 in those who received HiberixH. All were mild to moderate. No vaccine-related serious or grade 3 adverse events were observed. There was no increase in adverse events wit