Investigating novel approaches to the detection of virus neutralising antibodies to rabies and Rift Valley fever virus

Goldstein, Emily Jane (2016) Investigating novel approaches to the detection of virus neutralising antibodies to rabies and Rift Valley fever virus. PhD thesis, University of Glasgow.

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Abstract

Serosurveillance is a powerful tool fundamental to understanding infectious disease dynamics. The presence of virus neutralising antibody (VNAb) in sera is considered the best evidence of infection, or indeed vaccination, and the gold standard serological assay for their detection is the virus neutralisation test (VNT). However, VNTs are labour intensive, costly and time consuming. In addition, VNTs for the detection of antibodies to highly pathogenic viruses require the use of high containment facilities, restricting the application of these assays to the few laboratories with adequate facilities. As a result, robust serological data on such viruses are limited. In this thesis I develop novel VNTs for the detection of VNAb to two important, highly pathogenic, zoonotic viruses; rabies and Rift Valley fever virus (RVFV).

The pseudotype-based neutralisation test developed in this study allows for the detection of rabies VNAb without the requirement for high containment facilities. This assay was utilised to investigate the presence of rabies VNAb in animals from a variety of ecological settings. In this thesis I present evidence of natural rabies infection in both domestic dogs and lions from rabies endemic settings. The assay was further used to investigate the kinetics of VNAb response to rabies vaccination in a cohort of free-roaming dogs.

The RVFV neutralisation assay developed herein utilises a recombinant luciferase expressing RVFV, which allows for rapid, high-throughput serosurveillance of this important neglected pathogen. In this thesis I present evidence of RVFV infection in a variety of domestic and wildlife species from Northern Tanzania, in addition to the detection of low-level transmission of RVFV during interepidemic periods. Additionally, the investigation of a longitudinal cohort of domestic livestock also provided evidence of rapid waning of RVF VNAb following natural infection.

Collectively, the serological data presented in this thesis are consistent with existing data in the literature generated using the gold standard VNTs. Increasing the availability of serological assays will allow the generation of robust serological data, which are imperative to enhancing our understanding of the complex, multi-host ecology of these two viruses.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: rabies virus, Rift Valley fever virus, neutralising antibodies, neutralizing antibodies, serology, pseudotypes, pseudotype, veterinary serology.
Subjects: Q Science > QR Microbiology > QR355 Virology
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation > Centre for Virus Research
Supervisor's Name: Willett, Professor Brian and Hosie, Professor Margaret and Cleaveland, Professor Sarah
Date of Award: 2016
Depositing User: Miss Emily Goldstein
Unique ID: glathesis:2016-7617
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 04 Oct 2016 09:06
Last Modified: 21 Oct 2016 12:14
URI: http://theses.gla.ac.uk/id/eprint/7617

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