eprintid: 10110080 rev_number: 15 eprint_status: archive userid: 608 dir: disk0/10/11/00/80 datestamp: 2020-09-15 09:40:51 lastmod: 2021-09-17 22:32:33 status_changed: 2020-09-15 09:40:51 type: article metadata_visibility: show creators_name: Modi, T creators_name: Gervais, D creators_name: Smith, S creators_name: Miller, J creators_name: Subramaniam, S creators_name: Thalassinos, K creators_name: Shepherd, A title: Characterization of the UK anthrax vaccine and human immunogenicity ispublished: inpress divisions: UCL divisions: B02 divisions: C08 divisions: D09 divisions: G03 keywords: Bacillus anthracis, anthrax, anthrax vaccine precipitated, desorption, proteomics, MHC-binding prediction note: Copyright © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. abstract: The manufacture of the UK Anthrax vaccine (AVP) focuses on the production of Protective Antigen (PA) from the Bacillus anthracis Sterne strain. Although used for decades, several of AVP’s fundamental properties are poorly understood, including its exact composition, the extent to which proteins other than PA may contribute to protection, and whether the degree of protection varies between individuals. This study involved three innovative investigations. Firstly, the composition of AVP was analyzed using liquid chromatography tandem mass-spectrometry (LC-MS/MS), requiring the development of a novel desorption method for releasing B. anthracis proteins from the vaccine’s aluminum-containing adjuvant. Secondly, computational MHC-binding predictions using NetMHCIIpan were made for the eight most abundant proteins of AVP, for the commonest HLA alleles in multiple ethnic groups, and for multiple B. anthracis strains. Thirdly, antibody levels and toxin neutralizing antibody (TNA) levels were measured in sera from AVP human vaccinees for both PA and Lethal Factor (LF). It was demonstrated that AVP is composed of at least 138 B. anthracis proteins, including PA (65%), LF (8%) and Edema Factor (EF) (3%), using LC-MS/MS. 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 between different HLA alleles. These analyses highlight two important properties of the AVP vaccine that have not been established previously. Firstly, the effectiveness of AVP within humans may 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, these are unlikely to affect the cross-strain protection afforded by AVP. date: 2020-09-08 date_type: published publisher: Informa UK Limited official_url: https://doi.org/10.1080/21645515.2020.1799668 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1812777 doi: 10.1080/21645515.2020.1799668 lyricists_name: Shepherd, Adrian lyricists_name: Thalassinos, Konstantinos lyricists_id: AJSHE04 lyricists_id: KTHAL22 actors_name: Austen, Jennifer actors_id: JAUST66 actors_role: owner full_text_status: public publication: Human Vaccines & Immunotherapeutics citation: Modi, T; Gervais, D; Smith, S; Miller, J; Subramaniam, S; Thalassinos, K; Shepherd, A; (2020) Characterization of the UK anthrax vaccine and human immunogenicity. Human Vaccines & Immunotherapeutics 10.1080/21645515.2020.1799668 <https://doi.org/10.1080/21645515.2020.1799668>. (In press). Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10110080/1/Characterization%20of%20the%20UK%20anthrax%20vaccine%20and%20human%20immunogenicity.pdf