{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:11:53Z","timestamp":1760231513823,"version":"build-2065373602"},"reference-count":50,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T00:00:00Z","timestamp":1663632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH-NIAID","doi-asserted-by":"publisher","award":["HHSN266200400084C"],"award-info":[{"award-number":["HHSN266200400084C"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>The causative agent of anthrax, Bacillus anthracis, evades the host immune response and establishes infection through the production of binary exotoxins composed of Protective Antigen (PA) and one of two subunits, lethal factor (LF) or edema factor (EF). The majority of vaccination strategies have focused upon the antibody response to the PA subunit. We have used a panel of humanised HLA class II transgenic mouse strains to define HLA-DR-restricted and HLA-DQ-restricted CD4+ T cell responses to the immunodominant epitopes of PA. This was correlated with the binding affinities of epitopes to HLA class II molecules, as well as the responses of two human cohorts: individuals vaccinated with the Anthrax Vaccine Precipitated (AVP) vaccine (which contains PA and trace amounts of LF), and patients recovering from cutaneous anthrax infections. The infected and vaccinated cohorts expressing different HLA types were found to make CD4+ T cell responses to multiple and diverse epitopes of PA. The effects of HLA polymorphism were explored using transgenic mouse lines, which demonstrated differential susceptibility, indicating that HLA-DR1 and HLA-DQ8 alleles conferred protective immunity relative to HLA-DR15, HLA-DR4 and HLA-DQ6. The HLA transgenics enabled a reductionist approach, allowing us to better define CD4+ T cell epitopes. Appreciating the effects of HLA polymorphism on the variability of responses to natural infection and vaccination is vital in planning protective strategies against anthrax.<\/jats:p>","DOI":"10.3390\/vaccines10101571","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:08:09Z","timestamp":1663718889000},"page":"1571","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Impact of HLA Polymorphism on the Immune Response to Bacillus Anthracis Protective Antigen in Vaccination versus Natural Infection"],"prefix":"10.3390","volume":"10","author":[{"given":"Stephanie","family":"Ascough","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Imperial College, London W12 0NN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca J.","family":"Ingram","sequence":"additional","affiliation":[{"name":"Wellcome-Wolfson Institute of Experimental Medicine, Queen\u2019s University Belfast, Belfast BT7 1NN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen K. Y.","family":"Chu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Imperial College, London W12 0NN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen J.","family":"Moore","sequence":"additional","affiliation":[{"name":"Sanofi, South San Francisco, CA 94080, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresa","family":"Gallagher","sequence":"additional","affiliation":[{"name":"BioMET, School of Medicine, University of Maryland, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugh","family":"Dyson","sequence":"additional","affiliation":[{"name":"Defence Science Technology Laboratory, Porton Down, Salisbury SP4 0JQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehmet","family":"Doganay","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Erciyes University Hospital, Kayseri 38095, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2676-4557","authenticated-orcid":false,"given":"G\u00f6khan","family":"Metan","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Clinical Microbiology, Hacettepe University Faculty of Medicine Ankara, Ankara 06000, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusuf","family":"Ozkul","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Erciyes University Hospital, Kayseri 38095, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Les","family":"Baillie","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff CF24 4HQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0322-5972","authenticated-orcid":false,"given":"E. Diane","family":"Williamson","sequence":"additional","affiliation":[{"name":"Defence Science Technology Laboratory, Porton Down, Salisbury SP4 0JQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John H.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Institute for Cellular Medicine, Newcastle University, Newcastle upon Tyne NE1 7RU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernard","family":"Maillere","sequence":"additional","affiliation":[{"name":"CEA-Saclay, D\u00e9partement M\u00e9dicaments et Technologies pour la Sant\u00e9, Universit\u00e9 Paris-Saclay, 91192 Gif-sur-Yvette, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosemary J.","family":"Boyton","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Imperial College, London W12 0NN, UK"},{"name":"Lung Division, Royal Brompton and Harefield Hospitals, Guy\u2019s and St Thomas\u2019 NHS Foundation Trust, London SE1 9RT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2436-6192","authenticated-orcid":false,"given":"Daniel M.","family":"Altmann","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Imperial College, London W12 0NN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"20","DOI":"10.12998\/wjcc.v3.i1.20","article-title":"Anthrax: A disease of biowarfare and public health importance","volume":"3","author":"Goel","year":"2015","journal-title":"World J. 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