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Characterisation of T cell responses to bovine viral diarrhoea virus proteins and its applications towards the development of improved vaccines

Njeri, Victor R. (2015) Characterisation of T cell responses to bovine viral diarrhoea virus proteins and its applications towards the development of improved vaccines Doctoral thesis, University of Surrey.

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Abstract

Bovine viral diarrhoea virus (BVDV) is an important pathogen that causes infectious disease of cattle worldwide and results in significant economic losses. Vaccination has long been used as a tool for control of BVDV but inadequacies of existing vaccines have hampered eradication efforts. Attempts to develop sub-unit vaccines have focused on the structural envelope protein E2, which is a dominant target of neutralising antibodies and as well as CD4 T cell responses. This study aimed to rationally address the development of more efficacious vaccines by characterising the kinetics and specificity of T cell responses to a BVDV type 1 peptide library in calves rendered immune to BVDV following recovery from experimental infection. Upon identification of E2 and NS3 as the dominant targets of CD4 T cell responses, we assessed whether T cells induced by one virus genotype were capable of responding to a heterologous virus genotype and to identified E2 and NS3 as targets of genotype-specific and genotype transcending responses, respectively. This finding strengthened the argument for inclusion of both antigens in a subunit vaccine formulation. A nanoparticulate formulation of E2 and NS3 adjuvanted with poly(I:C) was shown to induce protective responses comparable to a commercial available BVDV vaccine in a vaccination and challenge experiment. It is hoped that the data generated will have implications for the design of improved vaccines against BVD.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors :
AuthorsEmailORCID
Njeri, Victor R.v.njeri@surrey.ac.ukUNSPECIFIED
Date : 30 January 2015
Contributors :
ContributionNameEmailORCID
Thesis supervisorLocker, Nn.locker@surrey.ac.ukUNSPECIFIED
Thesis supervisorGraham, SPs.graham@surrey.ac.ukUNSPECIFIED
Depositing User : Victor Njeri
Date Deposited : 13 Feb 2015 10:25
Last Modified : 30 Jan 2016 02:08
URI: http://epubs.surrey.ac.uk/id/eprint/807071

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