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Secreted neisserial proteins as potential vaccines or tools for biotechnology

Harding, Samuel (2016) Secreted neisserial proteins as potential vaccines or tools for biotechnology. MPhil thesis, University of Sheffield.

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N. meningitidis is a Gram negative, human specific pathogen which is one of the leading causes of bacterial meningitis worldwide. Despite the severity of the disease the current available vaccines do not provide complete protection against infection therefore prompting research into other proteins which have potential as vaccine targets. A variety of possible virulence factors have been found for this pathogen including IgA1 protease which has been attributed with immune evasion and causing severe inflammation. It has also been noted that natural antibodies to IgA1P persist in the body for five years or longer post infection or carriage of N. meningitidis. All of these factors suggest a role in virulence determination and the potential for the use of IgA1P and its co-secreted peptides as potential vaccine targets. This report outlines how the α and c-γ-α proteins, which are co-secreted alongside neisserial IgA1P, underwent several trials in order to elucidate structural data and cross-linking experiments which have determined a potential binding partner in the circulation system. Further the potential of α as a vaccine carrier protein has been evaluated, showing that it boosts immune response to other proteins when inoculated alongside them. In parallel with this work neisserial IgA1P protein has undergone multiple mutagenesis reactions creating inactive and easier to purify versions of the protein which can be used in future structural and functional trials.

Item Type: Thesis (MPhil)
Academic Units: The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Medicine (Sheffield)
Depositing User: Mr Samuel Harding
Date Deposited: 24 Feb 2017 14:45
Last Modified: 22 Feb 2019 01:18
URI: http://etheses.whiterose.ac.uk/id/eprint/16265

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