{"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":1791653758643,"version":"4.3.4"},"reference-count":49,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T00:00:00Z","timestamp":1701216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000774","name":"Defense Threat Reduction Agency\u2019s (DTRA) Joint Science and Technology Office (JSTO) for Chemical and Biological Defense (CBD)","doi-asserted-by":"publisher","award":["CB-CALL12-VAXV2-2-0175"],"award-info":[{"award-number":["CB-CALL12-VAXV2-2-0175"]}],"id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Venezuelan equine encephalitis virus (VEEV) outbreaks occur sporadically. Additionally, VEEV has a history of development as a biothreat agent. Yet, no FDA-approved vaccine or therapeutic exists for VEEV disease. The sporadic outbreaks present a challenge for testing medical countermeasures (MCMs) in humans; therefore, well-defined animal models are needed for FDA Animal Rule licensure. The cynomolgus macaque (CM) model has been studied extensively at high challenge doses of the VEEV Trinidad donkey strain (&gt;1.0 \u00d7 108 plaque-forming units [PFU]), doses that are too high to be a representative human dose. Based on viremia of two subtypes of VEEV, IC, and IAB, we found the CM infectious dose fifty (ID50) to be low, 12 PFU, and 6.7 PFU, respectively. Additionally, we characterized the pattern of three clinical parameters (viremia, temperature, and lymphopenia) across a range of doses to identify a challenge dose producing consistent signs of infection. Based on these studies, we propose a shift to using a lower challenge dose of 1.0 \u00d7 103 PFU in the aerosol CM model of VEEV disease. At this dose, NHPs had the highest viremia, demonstrated a fever response, and had a measurable reduction in complete lymphocyte counts\u2014biomarkers that can demonstrate MCM efficacy.<\/jats:p>","DOI":"10.3390\/v15122351","type":"journal-article","created":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T12:01:00Z","timestamp":1701259260000},"page":"2351","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Defining the Cynomolgus Macaque (Macaca fascicularis) Animal Model for Aerosolized Venezuelan Equine Encephalitis: Importance of Challenge Dose and Viral Subtype"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8734-8912","authenticated-orcid":false,"given":"Crystal W.","family":"Burke","sequence":"first","affiliation":[{"name":"Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina L.","family":"Gardner","sequence":"additional","affiliation":[{"name":"Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimee I.","family":"Goodson","sequence":"additional","affiliation":[{"name":"Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley E.","family":"Piper","sequence":"additional","affiliation":[{"name":"Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5838-9026","authenticated-orcid":false,"given":"Rebecca A.","family":"Erwin-Cohen","sequence":"additional","affiliation":[{"name":"Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4359-9984","authenticated-orcid":false,"given":"Charles E.","family":"White","sequence":"additional","affiliation":[{"name":"Statistics Division, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela J.","family":"Glass","sequence":"additional","affiliation":[{"name":"Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"},{"name":"Risk Management Office, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,29]]},"reference":[{"key":"ref_1","first-page":"43","article-title":"Equine Encephalomyelitis in Venezuela: Advance Data Concerning the Causative Agent","volume":"3","author":"Kubes","year":"1939","journal-title":"Can. 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