The Library
Vaccine trials against canine leishmaniasis
Tools
Carson, Connor (2010) Vaccine trials against canine leishmaniasis. PhD thesis, University of Warwick.
PDF
WRAP_THESIS_Carson_2010.pdf - Requires a PDF viewer. Download (2615Kb) |
Official URL: http://webcat.warwick.ac.uk/record=b2338410~S15
Abstract
Zoonotic visceral leishmaniasis (ZVL) is a fatal disease caused by the sandfly-borne
intracellular protozoan parasite Leishmania infantum, and vaccine development in the
reservoir host (the domestic dog) is a current research priority. The aims of this study were
(1) to conduct safety and immunogenicity trials of two candidate vaccines in dogs, and (2)
to compare and demonstrate the utility of immunological and molecular tools for
measurement of vaccine efficacy in naturally exposed dogs.
DNA/ modified vaccinia virus Ankara (MVA) prime/boost canine vaccines expressing the
Leishmania proteins TRYP and LACK were safe, and elicited a type-1 cytokine response,
in vivo delayed-type hypersensitivity and IgG2 class responses, consistent with superior
protective immunogenicity of TRYP over LACK. However, inconsistent associations were
found between progressive disease in infected dogs and IgG class levels, prompting
caution in use of the latter as a proxy for protective immunogenicity. Specific serological
responses in vaccinated dogs did not cross-react with an unrelated diagnostic antigen
rK39, and responses to crude parasite antigen (CLA) were minimal, enabling serological
detection of infection incidence in vaccinated dogs. Particularly in early stage infection,
CLA ELISA was more sensitive than rK39 ELISA and an rK39-based rapid diagnostic
test, though rK39 serology was sensitive for diagnosis of symptomatic clinical cases.
A commercially available PCR kit incorporating a rapid oligochromatographic detection
step was tested for the first time in dogs, and proved highly sensitive for detection of ZVL
infection in bone marrow, comparable to existing nested PCR methods. Molecular
methods were investigated as proxy measures to replace labour-intensive xenodiagnosis
for detection of the infectiousness of dogs to biting sand flies. Conventional and real-time
PCR of tissues from naturally infected dogs were sensitive tests to identify infectiousness,
but showed low to moderate specificity. Recommendations are made to improve the
application of molecular methods as proxy measures of infectiousness and hence vaccine
efficacy.
Item Type: | Thesis (PhD) | ||||
---|---|---|---|---|---|
Subjects: | Q Science > QL Zoology R Medicine > RA Public aspects of medicine |
||||
Library of Congress Subject Headings (LCSH): | Kala-azar -- Vaccination, Dogs -- Vaccination, Dogs -- Infections | ||||
Official Date: | January 2010 | ||||
Dates: |
|
||||
Institution: | University of Warwick | ||||
Theses Department: | Department of Biological Sciences | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Courtenay, Orin | ||||
Sponsors: | Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC) ; Pfizer Animal Health | ||||
Extent: | x, 193 leaves : charts | ||||
Language: | eng |
Request changes or add full text files to a record
Repository staff actions (login required)
View Item |
Downloads
Downloads per month over past year