A randomized and controlled Phase 1 study of the safety and immunogenicity of the AMA1-C1/Alhydrogel + CPG 7909 vaccine for Plasmodium falciparum malaria in semi-immune Malian adults

Abstract

A double blind, randomized and controlled Phase 1 clinical trial was conducted to assess the safety and immunogenicity in malaria-exposed adults of the Plasmodium falciparum blood stage vaccine candidate Apical Membrane Antigen 1-Combination 1 (AMA1-C1)/Alhydrogel with and without the novel adjuvant CPG 7909. Participants were healthy adults 18-45 years old living in the village of Donéguébougou, Mali. A total of 24 participants received 2 doses one month apart of either 80 microg AMA1-C1/Alhydrogel or 80 microg AMA1-C1/Alhydrogel + 564 microg CPG 7909. The study started in October 2007 and completed follow up in May 2008. Both vaccines were well tolerated, with only mild local adverse events and no systemic adverse events judged related to vaccination. The difference in antibody responses were over 2-fold higher in the group receiving CPG 7909 for all time points after second vaccination and the differences are statistically significant (all p<0.05). This is the first use of the novel adjuvant CPG 7909 in a malaria-exposed population.

Figure 1

AMA1-C1 antibody response over time. Geometric mean and 95% pointwise confidence intervals for each group are shown. Participants were immunized on Days 0 and 28, and antibody responses were measured on Days 0, 14, 28, 42, 60, 90, and 210. Arrows indicate immunization days.

Figure 2

Adjusted AMA1-C1 antibody response on Day 42. Adjusted antibody response was calculated by subtracting Day 0 response from Day 42 response for each person. Adjusted response for all individuals and the geometric mean are shown.

Figure 3

Growth-inhibitory activity of Days 0 and 42 IgGs. Total IgG was purified individually by Protein G purification. IgGs from Alum group (A and C) and Alum+CPG group (B and D) were tested against either P. falciparum FVO (A and B) or 3D7 (C and D) parasites at 10.5 mg/mL in GIA well.