Phase 1 safety and immunogenicity trial of the Plasmodium falciparum blood-stage malaria vaccine AMA1-C1/ISA 720 in Australian adults

Abstract

A Phase 1 trial was conducted in malaria-naïve adults to evaluate the recombinant protein vaccine apical membrane antigen 1 – Combination 1 (AMA1-C1) formulated in Montanide(®) ISA 720 (SEPPIC, France), a water-in-oil adjuvant. Vaccinations were halted early due to a formulation issue unrelated to stability or potency. Twenty-four subjects (12 in each group) were enrolled and received 5 or 20 μg protein at 0 and 3 months and 4 subjects were enrolled and received one vaccination of 80 μg protein. After first vaccination, nearly all subjects experienced mild to moderate local reactions and 6 experienced delayed local reactions occurring at day 9 or later. After the second vaccination, 3 subjects experienced transient grade 3 (severe) local reactions; the remainder experienced grade 1 or 2 local reactions. All related systemic reactogenicity was grade 1 or 2, except 1 instance of grade 3 malaise. Anti-AMA1-C1 antibody responses were dose dependent and seen following each vaccination, with mean antibody levels 2-3 fold higher in the 20 μg group compared to the 5 μg group at most time points. In vitro growth-inhibitory activity was a function of the anti-AMA1 antibody titer. AMA1-C1 formulated in ISA 720 is immunogenic in malaria-naïve Australian adults. It is reasonably tolerated, though some transient, severe, and late local reactions are seen