Peer-Reviewed Journal Details
Mandatory Fields
Prieur, E.,Gilbert, S. C.,Schneider, J.,Moore, A. C.,Sheu, E. G.,Goonetilleke, N.,Robson, K. J.,Hill, A. V.
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
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
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.
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