Experimental Vaccine for Malaria in Adults in Mali

The purpose of this Phase 1 clinical trial is to evaluate the safety and immunogenicity of the Plasmodium falciparum malaria vaccine AMA1-C1/Alhydrogel, in healthy malaria-exposed adult volunteers. Between 2-3 million deaths occur each year as a result of malaria. Most of these deaths are a result of P. falciparum malaria, in children under five years of age, in sub-Saharan Africa. A safe and effective vaccine that would reduce both morbidity and mortality secondary to P. falciparum would be a valuable resource in the fight against this disease. The apical membrane antigen 1 (AMA1) is a surface protein expressed during the asexual blood stage of P. falciparum that is thought to play a role in parasite invasion of erythrocytes. Clinical symptoms of malaria in humans are due to the asexual blood stage. Therefore, this vaccine was designed to protect an individual from illness due to the asexual stage of P. falciparum infection by inhibiting parasite invasion of erythrocytes. The AMA1-C1/Alhydrogel vaccine preparations to be studied contain an equal mixture of AMA1 from two different clones of Plasmodium falciparum (FVO and 3D7), both produced separately as recombinant proteins expressed by Pichia pastoris (AMA1 FVO and AMA1 3D7). This vaccine has been tested in one clinical trial of 30 malaria-unexposed human adults in the United States and no clinically significant risks have been identified. The study will be conducted in Don gu bougou, Mali, and will be a blinded, randomized and controlled trial that will evaluate three dose levels of AMA1-C1 (5 micro g, 20 micro g, 80 micro g). Fifty-four healthy male and non-pregnant female volunteers ages 18 to 45 will be enrolled. Eighteen volunteers will be assigned to each of the three dose groups. Within each group, twelve volunteers will be randomized to receive either a 5 micro g, 20 micro g, or 80 micro g dose of AMA1-Cl/Alhydrogel and 6 will be randomized to receive the tetanus toxoid vaccine. Immunizations will be administered by intramuscular injection on months 0, 1, and 12. The groups will be staggered such that adequate safety evaluation can be performed prior to dose escalation. The duration of the study is 18 months per volunteer. The primary objective of this trial is to determine the frequency and severity of vaccine-related adverse events for each dose. The secondary objective is to determine the dose that generates the highest serum antibody levels to AMA1 antigen at Day 42.