The construction and characterization of recombinant sindbis virus vectors as a platform for anthrax vaccine development

The intentional release of anthrax spores in the U. S. mail system and the subsequent fatalities have renewed interest in developing therapeutics to protect against B. anthracis. Anthrax Vaccine Adsorbed (AVA) is the only licensed vaccine preparation currently used however, immunogenicity is variable and the boosting regimen is long-term and must be maintained to ensure continued protection. Protective antigen (PA), the chief component of AVA, is an 83kDa protein responsible for binding host cell receptors and promoting toxin entry into susceptible cells. Analysis of the PA molecule has identified a specific region, termed domain four, that contains epitopes responsible for antibody binding. Sindbis virus, the prototypical member of the genus alphavirus, has been extensively used as a vector of foreign gene expression. Several characteristics, including ease of manipulation, high levels of transgenic expression, and lack of pathogenicity in humans make Sindbis virus an attractive candidate as a vaccine vector. The purpose of this proposal is to construct and characterize replication-competent Sindbis virus vaccine vectors that express PA using in vivo and in vitro analysis in order to generate a recombinant viral vaccine capable of providing protection from virulent anthrax spore challenge.

Name thesis:degree_name

PhD

Level thesis:degree_level

Doctoral

Grantor

The University of Texas Medical Branch

Year dc:date.issued

2008

Author dc:creator

• Thomas, John

Advisor dc:contributor.advisor

• Johnny W. Peterson

Committee members dc:contributor.committeemember

• Thomas Wood
• Rolf Konig
• Hans Heidner

• t cell
• spore
• Sindbis
• dendritic cell
• anthrax
• Ames

Statement dc:rights

• Copyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works.

Language dc:language.iso

eng

Dc Identifier Other

etd-12012008-120339

OAI identifier oai:identifier

oai:utmb-ir.tdl.org:2152.3/278