Phase I trial of two recombinant vaccines containing the 19kd carboxy terminal fragment of Plasmodium falciparum merozoite surface protein 1 (msp-1 19) and T helper epitopes of tetanus toxoid

Abstract

The safety and immunogenicity of 2 yeast-derived, blood-stage malaria vaccines were evaluated in a phase l trial. Healthy adults were given 2 or 3 doses of alum-adsorbed vaccine containing the 19 kDa carboxy-terminal fragment of the merozoite surface protein-1 (MSP-1 19) derived from the 3D7 or the FVO strain of Plasmodium falciparum fused to tetanus toxoid T-helper epitopes P30 and P2. The first 2 doses of MSP-1 19 were well tolerated. Hypersensitivity reactions occurred in 3 subjects after the third dose of MSP-1 19, including bilateral injection site reactions in 2 (one with generalized skin rash), and probable histamine-associated hypotension in 1. Serum antibody responses to MSP-1 19 occurred in 5/16, 9/16 and 0/8 subjects given 20 μg of MSP-1 19, 200 μg of MSP-1 19, and control vaccines (hepatitis B or Td), respectively. Both MSP-1 19 vaccines were immunogenic in humans, but changes in formulation will be necessary to improve safety and immunogenicity profiles.