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Title: Cell mediated immune response to papilloma virus proteins
Author: Jain, S.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2003
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Development of a prophylactic or a therapeutic vaccine could significantly reduce the impact of anogenital papillomatosis and lower the incidence of cervical carcinoma. To develop such vaccines one needs to understand the natural host immune response elicited to fight these infections. Unfortunately this poses a problem in papillomaviruses since they are difficult to grow in tissue culture and they are species specific. Therefore use of an animal model for vaccine development is mandatory to understand host defence from the time of infection with virus through to the regression of lesions. The Canine Oral Papillomavirus (COPV) is a very good model to study immune responses and vaccine efficacy in papillomavirus infections as it is a mucosal papillomavirus in a well characterised laboratory species. For effective vaccine development it is essential that the potential vaccine is able to induce cellular as well as humoral immunity. There are many reports and pre-clinical studies in humans as well as animal models where virus like particles (VLPs) are being used as prophylactic vaccines and it has been shown that they induce good serum IgG antibody responses. However, little is known about the cell-mediated immune response which plays a key role in viral clearance in established infections. Also, the mechanisms underlying spontaneous regression of mucosal warts are poorly understood. The present investigation was undertaken to address antigen-specific cell mediated immune responses to papillomavirus antigens in the COPV model. The study started with development of various COPV-specific recombinant constructs which provided useful tools for the subsequent development of immunoassays (lymphoproliferation assay, IFN-γ ELISPOT and cytotoxicity assays) to characterise cellular immune responses to COPV early proteins. Cell mediated immune responses were detected in the natural life cycle as well as in vaccinated beagles. It was found that local immune responses were more pronounced than systemic responses. T-cell proliferative responses were detected for El, E2, E7 and E6 proteins and E2 was identified as the most promising target for vaccine design.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available