Protection against malaria by immunization with plasmid DNA encoding circumsporozoite protein.

作者：M Sedegah, Richard C. Hedstrom, Peter M. Hobart, Stephen L. Hoffman · 发表于：Proceedings of the National Academy of Sciences · 年份：1994 · DOI：10.1073/pnas.91.21.9866 · 被引用次数：451 · 研究领域：Escherichia coli research studies、Invertebrate Immune Response Mechanisms、Immunotherapy and Immune Responses

Immunization with irradiated sporozoites protects animals and humans against malaria, and the circumsporozoite protein is a target of this protective immunity. We now report that adjuvant-free intramuscular injection of mice with plasmid DNA encoding the Plasmodium yoelii circumsporozoite protein induced higher levels of antibodies and cytotoxic T lymphocytes against the P. yoelii circumsporozoite protein than did immunization with irradiated sporozoites. Mice immunized with this vaccine 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 protected against challenge with 10(2) sporozoites, and the protection was dependent on CD8+ T cells. These studies demonstrate the utility of 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 provides an important alternative for rapid identification of protective B- and T-cell epitopes and for construction of vaccines to prevent malaria and other infectious diseases.