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73 - DNA vaccines for humanherpesviruses

from Part VII - Vaccines and immunothgerapy

Published online by Cambridge University Press:  24 December 2009

By
Thomas G. Evans  and
Mary Wloch
Edited by
Ann Arvin ,
Gabriella Campadelli-Fiume ,
Edward Mocarski ,
Patrick S. Moore ,
Bernard Roizman ,
Richard Whitley  and
Koichi Yamanishi
Thomas G. Evans
Affiliation:
Vical Incorporated, San Diego, CA, USA
Mary Wloch
Affiliation:
Vical Incorporated, San Diego, CA, USA
Ann Arvin
Affiliation:
Stanford University, California
Gabriella Campadelli-Fiume
Affiliation:
Università degli Studi, Bologna, Italy
Edward Mocarski
Affiliation:
Emory University, Atlanta
Patrick S. Moore
Affiliation:
University of Pittsburgh
Bernard Roizman
Affiliation:
University of Chicago
Richard Whitley
Affiliation:
University of Alabama, Birmingham
Koichi Yamanishi
Affiliation:
University of Osaka, Japan
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Summary

General design of DNA vaccines

DNA vaccines are circular, double-stranded plasmid DNA (pDNA) molecules, which are capable of initiating the expression of protein antigens of interest when introduced into cells. For this purpose, the pDNA contains an eukaryotic expression cassette consisting of a transcriptional promoter, a protein coding sequence derived from the target antigen gene, and a transcriptional terminator (Fig. 73.1). Although many different promoters have been investigated, none have been shown to be clearly superior to the constitutive CMV IE promoter. DNA vaccines can consist of single genes on one plasmid, multiple genes on one plasmid, multiple plasmids, or a combination of the above. In biscistronic or tricistronic constructs, internal ribosomal entry sites (IRES) or equivalent sequences, dual or triple promoters, or cleavable linkage regions in fusion proteins can be used for expression of multiple genes. Upon transfer into cells, the pDNA enters the nucleus and transcribes a messenger RNA (mRNA) encoding the antigen of interest. The antigen can be identical to the wild-type protein of the pathogen, or can be genetically modified to improve immunogenicity and/or reduce toxicity to the host. The pDNA may also contain an antibiotic resistance gene and a bacterial origin of replication for growth and propagation in E. coli. Constructs using selection elements for bacterial replication other than antibiotic elements have also been utilized.

For vaccination, the purified pDNA is reconstituted in aqueous vehicles, or formulated and injected.

Type
Chapter
Information
Human Herpesviruses
Biology, Therapy, and Immunoprophylaxis
 , pp. 1306 - 1317
Publisher: Cambridge University Press
Print publication year: 2007

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