{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T17:35:58Z","timestamp":1791653758370,"version":"4.3.4"},"reference-count":91,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,8,31]],"date-time":"2019-08-31T00:00:00Z","timestamp":1567209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"U.S. DOD Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense","award":["JPEO-CBRND"],"award-info":[{"award-number":["JPEO-CBRND"]}]},{"name":"Joint Project Manager Medical Countermeasure Systems","award":["JPM-MCS"],"award-info":[{"award-number":["JPM-MCS"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Licensure of a vaccine to protect against aerosolized Venezuelan equine encephalitis virus (VEEV) requires use of the U.S. Food and Drug Administration (FDA) Animal Rule to assess vaccine efficacy as human studies are not feasible or ethical. An approach to selecting VEEV challenge strains for use under the Animal Rule was developed, taking into account Department of Defense (DOD) vaccine requirements, FDA Animal Rule guidelines, strain availability, and lessons learned from the generation of filovirus challenge agents within the Filovirus Animal Nonclinical Group (FANG). Initial down-selection to VEEV IAB and IC epizootic varieties was based on the DOD objective for vaccine protection in a bioterrorism event. The subsequent down-selection of VEEV IAB and IC isolates was based on isolate availability, origin, virulence, culture and animal passage history, known disease progression in animal models, relevancy to human disease, and ability to generate sufficient challenge material. Methods for the propagation of viral stocks (use of uncloned (wild-type), plaque-cloned, versus cDNA-cloned virus) to minimize variability in the potency of the resulting challenge materials were also reviewed. The presented processes for VEEV strain selection and the propagation of viral stocks may serve as a template for animal model development product testing under the Animal Rule to other viral vaccine programs. This manuscript is based on the culmination of work presented at the \u201cAlphavirus Workshop\u201d organized and hosted by the Joint Vaccine Acquisition Program (JVAP) on 15 December 2014 at Fort Detrick, Maryland, USA.<\/jats:p>","DOI":"10.3390\/v11090807","type":"journal-article","created":{"date-parts":[[2019,9,2]],"date-time":"2019-09-02T03:16:12Z","timestamp":1567394172000},"page":"807","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Approach to Strain Selection and the Propagation of Viral Stocks for Venezuelan Equine Encephalitis Virus Vaccine Efficacy Testing under the Animal Rule"],"prefix":"10.3390","volume":"11","author":[{"given":"Janice M.","family":"Rusnak","sequence":"first","affiliation":[{"name":"Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND), Joint Project Manager-Medical Countermeasure Systems (JMP-MCS), Joint Vaccine Acquisition Program (JVAP), 1564 Freedman Drive, Fort Detrick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela J.","family":"Glass","sequence":"additional","affiliation":[{"name":"Department of Virology, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), 1425 Porter Street, Fort Detrick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott C.","family":"Weaver","sequence":"additional","affiliation":[{"name":"Institute for Human Infections and Immunity, World Reference Center for Emerging Viruses and Arboviruses and Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol L.","family":"Sabourin","sequence":"additional","affiliation":[{"name":"Battelle Biomedical Research Center, 1425 Plain City-Georgesville Road, West Jefferson, OH 43162, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Glenn","sequence":"additional","affiliation":[{"name":"Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND), Joint Project Manager-Medical Countermeasure Systems (JMP-MCS), Joint Vaccine Acquisition Program (JVAP), 1564 Freedman Drive, Fort Detrick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Klimstra","sequence":"additional","affiliation":[{"name":"Center for Vaccine Research, University of Pittsburgh, 3501 Fifth Avenue, Pittsburgh, PA 15261, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher S.","family":"Badorrek","sequence":"additional","affiliation":[{"name":"Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND), Joint Project Manager-Medical Countermeasure Systems (JMP-MCS), Joint Vaccine Acquisition Program (JVAP), 1564 Freedman Drive, Fort Detrick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farooq","family":"Nasar","sequence":"additional","affiliation":[{"name":"Department of Virology, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), 1425 Porter Street, Fort Detrick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy A.","family":"Ward","sequence":"additional","affiliation":[{"name":"Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND), Joint Project Manager-Medical Countermeasure Systems (JMP-MCS), Joint Vaccine Acquisition Program (JVAP), 1564 Freedman Drive, Fort Detrick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1146\/annurev.ento.49.061802.123422","article-title":"Venezuelan equine encephalitis","volume":"49","author":"Weaver","year":"2004","journal-title":"Annu. 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