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Protection against Malaria by Immunization with Plasmid DNA Encoding Circumsporozoite Protein

Martha Sedegah, Richard Hedstrom, Peter Hobart and Stephen L. Hoffman
Proceedings of the National Academy of Sciences of the United States of America
Vol. 91, No. 21 (Oct. 11, 1994), pp. 9866-9870
Stable URL: http://www.jstor.org/stable/2365723
Page Count: 5
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Protection against Malaria by Immunization with Plasmid DNA Encoding Circumsporozoite Protein
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Abstract

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 105 sporozoites (>105 median infectious doses). Eighteen (68%) of 28 mice that received two or three doses of vaccine were protected against challenge with 102 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.

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