Neurovirulence, viscerotropism and immunogenicity of live attenuated yellow fever 17D vaccine virus in non-human primates.

Yellow fever vaccine associated neurovirulence and viscerotropism have been reported by various countries. In this study, the neurovirulence, viscerotropism and immunogenicity of yellow fever vaccine seed lots (master and working) and final product manufactured at Serum Institute of India (SII) were evaluated in cynomolgus monkeys. WHO reference virus 168-73 and Stamaril™ as a control vaccine was used for comparison.

Safety and toxicology assessment of sodium nitrite administered by intramuscular injection.

Intramuscular (IM) injection of nitrite (1-10 mg/kg) confers survival benefit and protects against lung injury after exposure to chlorine gas in preclinical models. Herein, we evaluated safety/toxicity parameters after single, and repeated (once daily for 7 days) IM injection of nitrite in male and female Sprague Dawley rats and Beagle dogs. The repeat dose studies were performed in compliance with the Federal Drug Administration's (FDA) Good Laboratory Practices Code of Federal Regulations (21 CFR Part 58).

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 more pathogenic compared to VEEV similarly to what is observed in humans.

NUC041, a Prodrug of the DNA Methytransferase Inhibitor 5-aza-2',2'-Difluorodeoxycytidine (NUC013), Leads to Tumor Regression in a Model of Non-Small Cell Lung Cancer.

5-aza-2′,2′-difluorodeoxycytidine (NUC013) has been shown to be significantly safer and more effective than decitabine in xenograft models of human leukemia and colon cancer. However, it suffers from a similar short half-life as other DNA methyltransferase inhibitors with a 5-azacytosine base, which is problematic for nucleosides that primarily target tumor cells in S phase. Because of the relative instability of 5-azanucleosides, a prodrug approach was developed to improve the pharmacology of NUC013.

Evaluation of the safety and biodistribution of M032, an attenuated herpes simplex virus type 1 expressing hIL-12, after intracerebral administration to aotus nonhuman primates.

Herpes simplex virus type 1 (HSV-1) mutants lacking the γ(1)34.5 neurovirulence loci are promising agents for treating malignant glioma. Arming oncolytic HSV-1 to express immunostimulatory genes may potentiate therapeutic efficacy.

Host gene expression signatures discriminate between ferrets infected with genetically similar H1N1 strains.

Different respiratory viruses induce virus-specific gene expression in the host. Recent evidence, including those presented here, suggests that genetically related isolates of influenza virus induce strain-specific host gene regulation in several animal models. Here, we identified systemic strain-specific gene expression signatures in ferrets infected with pandemic influenza A/California/07/2009, A/Mexico/4482/2009 or seasonal influenza A/Brisbane/59/2007.

Investigation of the mode of action underlying the tumorigenic response induced in B6C3F1 mice exposed orally to hexavalent chromium.

Chronic ingestion of high concentrations of hexavalent chromium [Cr(VI)] in drinking water induces intestinal tumors in mice. To investigate the mode of action (MOA) underlying these tumors, a 90-day drinking water study was conducted using similar exposure conditions as in a previous cancer bioassay, as well as lower (heretofore unexamined) drinking water concentrations. Tissue samples were collected in mice exposed for 7 or 90 days and subjected to histopathological, biochemical, toxicogenomic, and toxicokinetic analyses.

Course of seasonal influenza A/Brisbane/59/07 H1N1 infection in the ferret.

Every year, influenza viruses infect approximately 5-20% of the population in the United States leading to over 200,000 hospitalizations and 36,000 deaths from flu-related complications. In this study, we characterized the immune and pathological progression of a seasonal strain of H1N1 influenza virus, A/Brisbane/59/2007 in a ferret model. The immune response of the animals showed a dose-dependent increase with increased virus challenge, as indicated by the presence of virus specific IgG, IgM, and neutralizing antibodies.

Pathogenesis of a genogroup II human norovirus in gnotobiotic pigs.

We evaluated the gnotobiotic (Gn) pig as a model to study the pathogenesis of human norovirus (HuNoV) and to determine the target cells for viral replication. Sixty-five Gn pigs were inoculated with fecal filtrates of the NoV/GII/4/HS66/2001/US strain or with pig-passaged intestinal contents (IC) and euthanized acutely (n = 43) or after convalescence (n = 22). Age-matched Gn piglets (n = 14) served as mock-inoculated controls.

West Nile Virus detection in kidney, cloacal, and nasopharyngeal specimens.

We compared kidney tissue samples and cloacal and nasopharyngeal swab samples from field-collected dead crows and blue jays for West Nile virus surveillance. Compared to tissue samples, 35% more swab samples were false negative. Swab samples were usually positive only when the corresponding tissue sample was strongly positive.

Patterns of West Nile virus infection in Ohio blue jays: implications for initiation of the annual cycle.

West Nile virus (WNV) was first detected in North America in New York City in 1999 and rapidly moved westward. Understanding the mechanisms by which the amplification cycle is reinitiated each year increases our ability to predict epizootics and geographic expansion of the disease. Such understanding is enhanced by knowledge of the patterns of infection in the vertebrate reservoir hosts.

Intraocular nematodiasis caused by Parelaphostrongylus tenuis in an eland antelope (Taurotragus oryx).

A 10-mo-old female eland (Taurotragus oryx) at the Wilds exhibited recalcitrant, progressive unilateral uveitis for a 5-wk period, despite constant medical treatment. Unilateral enucleation was performed because of blindness and animal discomfort evidenced by continuous blepharospasm. Histopathologic examination of the eye demonstrated intraocular larvae morphologically consistent with Parelaphostrongylus tenuis, the first known case of intraocular P.