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/Alhydrogel (R) consists of an equal mixture of recombinant AMA1 from FVO and 3D7 clones of P. falciparum, adsorbed onto Alhydrogel (R). 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 mu g 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 Doneguebougou, Mali. Eighteen children in the first cohort were randomized 2:1 to receive either 20 mg AMA1-C1/Alhydrogel (R) or Haemophilus influenzae type b Hiberix (R) vaccine. Two weeks later 18 children in the second cohort were randomized 2: 1 to receive either 80 mg AMA1-C1/Alhydrogel (R) or Haemophilus influenzae type b Hiberix (R) 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 Hiberix (R). All were mild to moderate. No vaccine-related serious or grade 3 adverse events were observed. There was no increase in adverse events with increasing dose of vaccine or number of immunizations. In subjects who received the test vaccine, antibodies to AMA1 increased on Day 14 and peaked at Day 42, with changes from baseline significantly different from subjects who received control vaccine. Conclusion: AMA-C1 vaccine is well tolerated and immunogenic in children in this endemic area although the antibody response was short lived.