Peer-Reviewed Journal Details
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Prieur, E.,Gilbert, S. C.,Schneider, J.,Moore, A. C.,Sheu, E. G.,Goonetilleke, N.,Robson, K. J.,Hill, A. V.
2004
January
Proceedings of The National Academy of Sciences of The United States of America
A Plasmodium falciparum candidate vaccine based on a six-antigen polyprotein encoded by recombinant poxviruses
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Optional Fields
Animals Antigens, Protozoan/genetics CD8-Positive T-Lymphocytes/immunology Cytotoxicity, Immunologic Female Fowlpox virus/genetics Genetic Vectors Interferon Type II/biosynthesis Malaria Vaccines/genetics/*immunology Malaria, Falciparum/*immunology/*prevention & control Mice Mice, Inbred BALB C Mice, Inbred C57BL Plasmodium falciparum/genetics/*immunology Protozoan Proteins/genetics/immunology Research Support, Non-U.S. Gov't Vaccines, DNA/genetics/immunology Vaccinia virus/genetics
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To generate broadly protective T cell responses more similar to those acquired after vaccination with radiation-attenuated Plasmodium falciparum sporozoites, we have constructed candidate subunit malaria vaccines expressing six preerythrocytic antigens linked together to produce a 3240-aa-long polyprotein (L3SEPTL). This polyprotein was expressed by a plasmid DNA vaccine vector (DNA) and by two attenuated poxvirus vectors, modified vaccinia virus Ankara (MVA) and fowlpox virus of the FP9 strain. MVAL3SEPTL boosted anti-thrombospondin-related adhesive protein (anti-TRAP) and anti-liver stage antigen 1 (anti-LSA1) CD8(+) T cell responses when primed by single antigen TRAP- or LSA1-expressing DNAs, respectively, but not by DNA-L3SEPTL. However, prime boost regimes involving two heterologous viral vectors expressing L3SEPTL induced a strong cellular response directed against an LSA1 peptide located in the C-terminal region of the polyprotein. Peptide-specific T cells secreted IFN-gamma and were cytotoxic. IFN-gamma-secreting T cells specific for each of the six antigens were induced after vaccination with L3SEPTL, supporting the use of polyprotein inserts to induce multispecific T cells against P. falciparum. The use of polyprotein constructs in nonreplicating poxviruses should broaden the target antigen range of vaccine-induced immunity and increase the number of potential epitopes available for immunogenetically diverse human populations.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14694197
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