Safety and Immunogenicity of a Recombinant Plasmodium falciparum AMA1 Malaria Vaccine Adjuvanted with Alhydrogel™, Montanide ISA 720 or AS02

Background Plasmodium falciparum Apical Membrane Antigen 1 ( Pf AMA1) is a candidate vaccine antigen expressed by merozoites and sporozoites. It plays a key role in red blood cell and hepatocyte invasion that can be blocked by antibodies. Methodology/Principal Findings We assessed the safety and immunogenicity of recombinant Pf AMA1 in a dose-escalating, phase Ia trial. Pf AMA1 FVO strain, produced in Pichia pastoris , was reconstituted at 10 µg and 50 µg doses with three different adjuvants, Alhydrogel™ , Montanide ISA720 and AS02 Adjuvant System. Six randomised groups of healthy male volunteers, 8–10 volunteers each, were scheduled to receive three immunisations at 4-week intervals. Safety and immunogenicity data were collected over one year. Transient pain was the predominant injection site reaction (80–100%). Induration occurred in the Montanide 50 µg group, resulting in a sterile abscess in two volunteers. Systemic adverse events occurred mainly in the AS02 groups lasting for 1–2 days. Erythema was observed in 22% of Montanide and 59% of AS02 group volunteers. After the second dose, six volunteers in the AS02 group and one in the Montanide group who reported grade 3 erythema (>50 mm) were withdrawn as they met the stopping criteria. All adverse events resolved. There were no vaccine-related serious adverse events. Humoral responses were highest in the AS02 groups. Antibodies showed activity in an in vitro growth inhibition assay up to 80%. Upon stimulation with the vaccine, peripheral mononuclear cells from all groups proliferated and secreted IFNγ and IL-5 cytokines. Conclusions/Significance All formulations showed distinct reactogenicity profiles. All formulations with Pf AMA1 were immunogenic and induced functional antibodies. Trial Registration Clinicaltrials.gov NCT00730782