دورية أكاديمية

Accelerating Influenza Research: Vaccines, Antivirals, Immunomodulators and Monoclonal Antibodies. The Manufacture of a New Wild-Type H3N2 Virus for the Human Viral Challenge Model.

التفاصيل البيبلوغرافية
العنوان: Accelerating Influenza Research: Vaccines, Antivirals, Immunomodulators and Monoclonal Antibodies. The Manufacture of a New Wild-Type H3N2 Virus for the Human Viral Challenge Model.
المؤلفون: Daniel J Fullen, Nicolas Noulin, Andrew Catchpole, Hosnieh Fathi, Edward J Murray, Alex Mann, Kingsley Eze, Ganesh Balaratnam, Daryl W Borley, Anthony Gilbert, Rob Lambkin-Williams
المصدر: PLoS ONE, Vol 11, Iss 1, p e0145902 (2016)
بيانات النشر: Public Library of Science (PLoS), 2016.
سنة النشر: 2016
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: BACKGROUND:Influenza and its associated diseases are a major cause of morbidity and mortality. The United States Advisory Committee on Immunization Practices recommends influenza vaccination for everyone over 6 months of age. The failure of the flu vaccine in 2014-2015 demonstrates the need for a model that allows the rapid development of novel antivirals, universal/intra-seasonal vaccines, immunomodulators, monoclonal antibodies and other novel treatments. To this end we manufactured a new H3N2 influenza virus in compliance with Good Manufacturing Practice for use in the Human Viral Challenge Model. METHODS AND STRAIN SELECTION:We chose an H3N2 influenza subtype, rather than H1N1, given that this strain has the most substantial impact in terms of morbidity or mortality annually as described by the Centre for Disease Control. We first subjected the virus batch to rigorous adventitious agent testing, confirmed the virus to be wild-type by Sanger sequencing and determined the virus titres appropriate for human use via the established ferret model. We built on our previous experience with other H3N2 and H1N1 viruses to develop this unique model. HUMAN CHALLENGE AND CONCLUSIONS:We conducted an initial safety and characterisation study in healthy adult volunteers, utilising our unique clinical quarantine facility in London, UK. In this study we demonstrated this new influenza (H3N2) challenge virus to be both safe and pathogenic with an appropriate level of disease in volunteers. Furthermore, by inoculating volunteers with a range of different inoculum titres, we established the minimum infectious titre required to achieve reproducible disease whilst ensuring a sensitive model that can be translated to design of subsequent field based studies. TRIAL REGISTRATION:ClinicalTrials.gov NCT02525055.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1932-6203
Relation: http://europepmc.org/articles/PMC4711822?pdf=render; https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0145902
URL الوصول: https://doaj.org/article/c8c4e973c1824f749324bb715d0ecd01
رقم الأكسشن: edsdoj.8c4e973c1824f749324bb715d0ecd01
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:19326203
DOI:10.1371/journal.pone.0145902