Induction of CD4(+) T cell-dependent CD8(+) type 1 responses in humans by a malaria DNA vaccine |
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Authors: | Wang R Epstein J Baraceros F M Gorak E J Charoenvit Y Carucci D J Hedstrom R C Rahardjo N Gay T Hobart P Stout R Jones T R Richie T L Parker S E Doolan D L Norman J Hoffman S L |
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Affiliation: | Malaria Program, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. |
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Abstract: | We assessed immunogenicity of a malaria DNA vaccine administered by needle i.m. or needleless jet injection [i.m. or i.m./intradermally (i.d.)] in 14 volunteers. Antigen-specific IFN-gamma responses were detected by enzyme-linked immunospot (ELISPOT) assays in all subjects to multiple 9- to 23-aa peptides containing class I and/or class II restricted epitopes, and were dependent on both CD8(+) and CD4(+) T cells. Overall, frequency of response was significantly greater after i.m. jet injection. CD8(+)-dependent cytotoxic T lymphocytes (CTL) were detected in 8/14 volunteers. Demonstration in humans of elicitation of the class I restricted IFN-gamma responses we believe necessary for protection against the liver stage of malaria parasites brings us closer to an effective malaria vaccine. |
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