Publications

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severe encephalitis in cynomolgus macaques exposed to aerosolized eastern equine encephalitis virus.cynomolgus macaques exposed to an aerosol containing a virulent strain of eastern equine encephalitis (eee) virus developed neurological signs indicating encephalitis that corresponded with the onset of fever and an elevated heart rate. viremia was either transient or undetectable even in animals that succumbed to the illness. the onset of illness was dose dependent, but once a febrile response was observed, macaques were moribund within 36 h. simultaneously, a prominent leukocytosis was seen; 1 ...200717597459
combined alphavirus replicon particle vaccine induces durable and cross-protective immune responses against equine encephalitis viruses.alphavirus replicons were evaluated as potential vaccine candidates for venezuelan equine encephalitis virus (veev), western equine encephalitis virus (weev), or eastern equine encephalitis virus (eeev) when given individually or in combination (v/w/e) to mice or cynomolgus macaques. individual replicon vaccines or the combination v/w/e replicon vaccine elicited strong neutralizing antibodies in mice to their respective alphavirus. protection from either subcutaneous or aerosol challenge with ve ...201425122801
a chimeric sindbis-based vaccine protects cynomolgus macaques against a lethal aerosol challenge of eastern equine encephalitis virus.eastern equine encephalitis virus (eeev) is a mosquito-borne alphavirus that causes sporadic, often fatal disease outbreaks in humans and equids, and is also a biological threat agent. two chimeric vaccine candidates were constructed using a cdna clone with a sindbis virus (sinv) backbone and structural protein genes from either a north (sin/naeeev) or south american (sin/saeeev) strain of eeev. the vaccine candidates were tested in a nonhuman primate (nhp) model of eastern equine encephalitis ( ...201323333212
host and viral traits predict zoonotic spillover from mammals.the majority of human emerging infectious diseases are zoonotic, with viruses that originate in wild mammals of particular concern (for example, hiv, ebola and sars). understanding patterns of viral diversity in wildlife and determinants of successful cross-species transmission, or spillover, are therefore key goals for pandemic surveillance programs. however, few analytical tools exist to identify which host species are likely to harbour the next human virus, or which viruses can cross species ...201728636590
comparative pathology study of venezuelan, eastern, and western equine encephalitis viruses in non-human primates.venezuelan, eastern, and western equine encephalitis viruses (veev, eeev, and weev) are mosquito-borne viruses in the americas that cause central nervous system (cns) disease in humans and equids. in this study, we directly characterized the pathogenesis of veev, eeev, and weev in cynomolgus macaques following subcutaneous exposure because this route more closely mimics natural infection via mosquito transmission or by an accidental needle stick. our results highlight how eeev is significantly m ...202032755661
applications of minimally invasive multimodal telemetry for continuous monitoring of brain function and intracranial pressure in macaques with acute viral encephalitis.alphaviruses such as venezuelan equine encephalitis virus (veev) and eastern equine encephalitis virus (eeev) are arboviruses that can cause severe zoonotic disease in humans. both veev and eeev are highly infectious when aerosolized and can be used as biological weapons. vaccines and therapeutics are urgently needed, but efficacy determination requires animal models. the cynomolgus macaque (macaca fascicularis) provides a relevant model of human disease, but questions remain whether vaccines or ...202032584818
the utilization of advance telemetry to investigate critical physiological parameters including electroencephalography in cynomolgus macaques following aerosol challenge with eastern equine encephalitis virus.most alphaviruses are mosquito-borne and can cause severe disease in humans and domesticated animals. in north america, eastern equine encephalitis virus (eeev) is an important human pathogen with case fatality rates of 30-90%. currently, there are no therapeutics or vaccines to treat and/or prevent human infection. one critical impediment in countermeasure development is the lack of insight into clinically relevant parameters in a susceptible animal model. this study examined the disease course ...202134138849
physiological and immunological changes in the brain associated with lethal eastern equine encephalitis virus in macaques.aerosol exposure to eastern equine encephalitis virus (eeev) can trigger a lethal viral encephalitis in cynomolgus macaques which resembles severe human disease. biomarkers indicative of central nervous system (cns) infection by the virus and lethal outcome of disease would be useful in evaluating potential medical countermeasures, especially for therapeutic compounds. to meet requirements of the animal rule, a better understanding of the pathophysiology of eeev-mediated disease in cynomolgus ma ...202133534855
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