Degree Type

Dissertation

Date of Award

1993

Degree Name

Doctor of Philosophy

Department

Zoology and Genetics

Abstract

Prior to licensing of veterinary vaccines, it is essential to demonstrate that the use of the product is safe (e.g., use of the product will not have unexpected or undesirable effects on animals exposed to the agent or on the environment) and potent (e.g., produces the desired result). The projects described in this dissertation demonstrate research directed toward the development and improvement of safety and potency testing of veterinary vaccines from a regulatory perspective;In the first study, recombination between vaccine strains of pseudorabies virus (PRV) resulting in the creation of strains with undesirable virulence and antigenic combinations was demonstrated. Awareness of the potential for creating virulent strains with the antigenic profile of vaccine strains has resulted in more careful use of vaccines and may have decreased disruption of eradication programs due to misleading serologic data. In addition, regulatory policy now requires the assessment of recombination potential (and the consequences thereof) prior to licensing of modified-live vaccines using new strains of an agent;The second study involved safety assessment of live Salmonella sp. as vaccine vectors. This study demonstrated that the expression of inserted genes is dependent on the genetic background, resulting in the need to conduct safety testing of genetically engineered strains on the final construct;Using licensed erysipelas bacterins, the third study demonstrated that a strong immune response two weeks after vaccination did not necessarily predict sufficient immunity development to protect vaccinates from clinical signs of disease until market weight. Prior to these studies, a vaccinate was expected to develop a secondary response to exposure to the virulent agent that would protect the animal from disease. The results of this study demonstrate a need to prove durable immunity to market weight following label recommendations for all vaccines;The last two studies demonstrate the development of a monoclonal antibody to a protective immunogen of Erysipelothrix rhusiopathiae and an in vitro potency assay based on the monoclonal antibody. This assay is expected to replace animal potency testing of erysipelas bacterins, thus reducing costs, animal welfare concerns, and human exposure to the pathogen.

DOI

https://doi.org/10.31274/rtd-180813-9995

Publisher

Digital Repository @ Iowa State University, http://lib.dr.iastate.edu/

Copyright Owner

Louise Mary Henderson

Language

en

Proquest ID

AAI9531817

File Format

application/pdf

File Size

225 pages

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