PROTECTION AGAINST MALARIA BY IMMUNIZATION WITH PLASMID DNA ENCODING CIRCUMSPOROZOITE PROTEIN

Immunization with irradiated sporozoites protects animals and humans a gainst malaria, and the circumsporozoite protein is a target of this p rotective immunity. We now report that adjuvant-free intramuscular inj ection of mice with plasmid DNA encoding the Plasmodium yoelii circums porozoite protein induced higher levels of antibodies and cytotoxic T lymphocytes against the P. yoelii circumsporozoite protein than did im munization with irradiated sporozoites. Mice immunized with this vacci ne had an 86% reduction in liver-stage parasite burden after challenge with 5 x 10(5) sporozoites (>10(5) median infectious doses). Eighteen (68%) of 28 mice that received two or three doses of vaccine were pro tected against challenge with 10(2) sporozoites, and the protection wa s dependent on CD8(+) T cells. These studies demonstrate the utility o f plasmid DNA immunization against a nonviral infection. By obviating the requirement for peptide synthesis, expression and purification of recombinant proteins, and adjuvants, this method of immunization provi des an important alternative for rapid identification of protective B- and T-cell epitopes and for construction of vaccines to prevent malar ia and other infectious diseases.