Modi, Tapasvi Pravinkumar (2020) Characterisation of the human immune response from AVP vaccine against anthrax. PhD thesis, Birkbeck, University of London.
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Abstract
The UK Anthrax vaccine (AVP) is an alum precipitate of a sterile culture filtrate of the Bacillus anthracis Sterne strain designed to maximise the production of protective antigen (PA). Although AVP has been in use for decades, several of its fundamental properties are poorly understood, including its exact composition, the extent to which proteins other than PA may contribute to protection, and how the degree of protection may differ between individuals. This study involved three innovative investigations. Firstly, the composition of AVP was analysed using liquid chromatography tandem mass-spectrometry (LC-MS/MS). This required the development of a novel desorption method for releasing B. anthracis proteins from the vaccine’s aluminium-containing adjuvant. Secondly, computational MHC-binding predictions were made for the eight most abundant proteins of AVP using the NetMHCIIpan tool, focusing on the most common HLA alleles in several ethnic groups and multiple B. anthracis strains. Thirdly, antibody levels and toxin neutralising antibody (TNA) levels were measured for both PA and lethal factor (LF) in sera from AVP human vaccinees. Using LC-MS/MS it was demonstrated that AVP is composed of at least 138 B. anthracis proteins, including toxin proteins PA (65%), LF (8%) and edema factor (EF) (3%). NetMHCIIpan predicted that peptides from all eight abundant proteins are likely to be presented to T cells, a pre-requisite for protection; however, the number of such peptides varied considerably for different HLA alleles. These analyses highlighted two important properties of the AVP vaccine that have not been previously established. Firstly, the effectiveness of AVP within humans does not depend on PA alone; there is compelling evidence to suggest that LF has a protective role, with computational predictions suggesting that additional proteins may be important for individuals with specific HLA allele combinations. Secondly, in spite of differences in the sequences of key antigenic proteins from different B. anthracis strains, computational analysis suggested that these do not affect the protection that AVP affords to strains other than the vaccine’s source strain.
Metadata
| Item Type: | Thesis |
|---|---|
| Copyright Holders: | The copyright of this thesis rests with the author, who asserts his/her right to be known as such according to the Copyright Designs and Patents Act 1988. No dealing with the thesis contrary to the copyright or moral rights of the author is permitted. |
| Depositing User: | Acquisitions And Metadata |
| Date Deposited: | 10 Nov 2021 15:57 |
| Last Modified: | 01 Nov 2023 14:59 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/46677 |
| DOI: | https://doi.org/10.18743/PUB.00046677 |
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