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Title: Investigation into the use of feline CD40 ligand as an adjuvant in a DNA vaccine against feline immunodeficiency virus
Author: Brown, Abigail Louise
ISNI:       0000 0001 3483 6162
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2004
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Feline immunodeficiency virus (FIV) is a pathogenic virus that causes disease in the domestic cat. FIV is found worldwide and can give rise to an infection that is very similar to human immunodeficiency virus (HIV) and the syndrome that is aquired immunodeficiency syndrome (AIDS). As FIV is a significant pathogen of cats, is found worldwide and induces similar pathology to that induced by HIV, developing a vaccine to FIV would not only benefit the domestic cat population but would provide an insight into the requirements for a HIV vaccine. To further the research into a FIV vaccine, the main aim of this study was to evaluate feline CD40 ligand (CD40L) as an adjuvant in a DNA vaccine against FIV. Initially, the biological activity of the previously cloned feline CD40L was demonstrated using proliferation assays and a CD40L feeder layer system. Once the biological activity of feline CD40L had been proven, a FIV DNA construct was selected for use in a DNA vaccine. To determine whether CD40L would enhance the immune response to FIV, an immunogenicity trial was conducted in mice. BALB/c mice were injected with CD40L DNA alone, FIV DNA alone or FIV DNA and CD40L DNA together. A control group was inoculated with phosphate buffered saline (PBS) only. The study demonstrated that CD40L enhanced the humoral immune response in mice to FIV but the results of the cell- mediated immune response to FIV were inconclusive. Studies were also conducted in the cat. Specified pathogen free (SPF) cats were inoculated with FIV DNA alone, CD40L DNA alone, or FIV and CD40L DNA. A control group was inoculated with PBS only. This study demonstrated that CD40L enhanced the cell- mediated response to FIV, but no anti-viral antibodies were detected in any of the groups post-vaccination. To further test the efficacy of a CD40L adjuvanted FIV DNA vaccine, the vaccinated cats were challenged intraperitoneally (i.p) with the virulent FIV isolate FIV-Glasgow 8 (FIV-GL8). No cats developed sterilising immunity to the FIV challenge as all vaccinated cats became virus isolation positive; however overall the viral loads were lower in the FIV and CD40L vaccinated cats than in the other groups. In the vaccine trial it was noted that there was a degree of enhancement of infection in the groups that were inoculated with FIV DNA or CD40L DNA alone. The final part of this study investigated potential modes of enhancement of FIV infection.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available