A5001871712- Viral Infections and Vectors
- Viral Infections and Outbreaks Research
- Fire effects on ecosystems
- Vector-Borne Animal Diseases
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Mosquito-borne diseases and control
- Long-Term Effects of COVID-19
- SARS-CoV-2 detection and testing
- Viral gastroenteritis research and epidemiology
- interferon and immune responses
- Vehicle License Plate Recognition
- Virus-based gene therapy research
- COVID-19 and healthcare impacts
- Animal Virus Infections Studies
- Synthesis and Characterization of Heterocyclic Compounds
United States Army Medical Research Institute of Infectious Diseases
2015-2024
Tulane University
2007-2009
United States Army
2003
The emergence of SARS-CoV-2 has created an international health crisis, and small animal models mirroring human disease are essential for medical countermeasure (MCM) development. Mice refractory to infection owing low-affinity binding the murine angiotensin-converting enzyme 2 (ACE2) protein. Here, we evaluated pathogenesis in male female mice expressing ACE2 gene under control keratin 18 promoter (K18). In contrast nontransgenic mice, intranasal exposure K18-hACE2 animals different doses...
Animal models recapitulating human COVID-19 disease, especially severe are urgently needed to understand pathogenesis and evaluate candidate vaccines therapeutics. Here, we develop novel severe-disease animal for involving disruption of adaptive immunity in Syrian hamsters. Cyclophosphamide (CyP) immunosuppressed or
Human polyclonal antibodies generated from DNA-vaccinated, transchromosomal bovines protect against hantavirus pulmonary syndrome.
Abstract A worldwide effort to counter the COVID-19 pandemic has resulted in hundreds of candidate vaccines moving through various stages research and development, including several phase 1, 2 3 clinical trials. relatively small number these have been evaluated SARS-CoV-2 disease models, fewer a severe model. Here, DNA targeting spike protein delivered by jet injection, nCoV-S(JET), elicited neutralizing antibodies hamsters was protective both wild-type transiently immunosuppressed hamster...
Hantaviruses are high-priority emerging pathogens carried by rodents and transmitted to humans aerosolized excreta or, in rare cases, person-to-person contact. While infections relatively rare, mortality rates range from 1 40% depending on the hantavirus species. There currently no FDA-approved vaccines or therapeutics for hantaviruses, only treatment infection is supportive care respiratory kidney failure. Additionally, human humoral immune response incompletely understood, especially...
Sin Nombre virus (SNV; family Bunyaviridae, genus Hantavirus) causes a hemorrhagic fever known as hantavirus pulmonary syndrome (HPS) in North America. There have been approximately 200 fatal cases of HPS the United States since 1993, predominantly healthy working-age males (case fatality rate 35%). are no FDA-approved vaccines or drugs to prevent treat HPS. Previously, we reported that based on full-length M gene segment Andes (ANDV) for South America, and Hantaan (HTNV) Puumala (PUUV) with...
ABSTRACT Sin Nombre virus (SNV) is a rodent-borne hantavirus that causes pulmonary syndrome (HPS) predominantly in North America. SNV infection of immunocompetent hamsters results an asymptomatic infection; the only lethal disease model for pathogenic Andes (ANDV) Syrian hamsters. Efforts to create by repeatedly passaging through hamster have demonstrated increased dissemination but no signs disease. In this study, we demonstrate immunosuppression administration combination dexamethasone and...
Andes virus (ANDV) is the predominant cause of hantavirus pulmonary syndrome (HPS) in South America and only known to be transmitted person-to-person. There are no vaccines, prophylactics, or therapeutics prevent treat this highly pathogenic disease (case-fatality 35–40%). Infection Syrian hamsters with ANDV results a that closely mimics human HPS incubation time, symptoms respiratory distress, pathology. Here, we evaluated feasibility two postexposure prophylaxis strategies ANDV/hamster...
Andes virus (ANDV) and ANDV-like viruses are responsible for most hantavirus pulmonary syndrome (HPS) cases in South America. Recent studies Chile indicate that passive transfer of convalescent human plasma shows promise as a possible treatment HPS. Unfortunately, availability from survivors this lethal disease is very limited. We interested exploring the concept using DNA vaccine technology to produce antiviral biologics, including polyclonal neutralizing antibodies use humans. Geese IgY an...
Background: Hantaviruses are zoonotic agents that cause hemorrhagic fevers and thought to be transmitted humans by exposure aerosolized excreta of infected rodents. Puumala virus (PUUV) is the predominant endemic hantavirus in Europe. A large proportion PUUV-infected patients suffer from gastrointestinal symptoms unclear origin. In this study we demonstrate PUUV infection can occur via alimentary tract. Methods: We investigated susceptibility human small intestinal epithelium for analyzed...
ABSTRACT Puumala virus (PUUV) is a causative agent of hemorrhagic fever with renal syndrome (HFRS). Although PUUV-associated HFRS does not result in high case-fatality rates, the social and economic impact considerable. There no licensed vaccine or specific therapeutic to prevent treat HFRS. Here we report synthesis codon-optimized, full-length M segment open reading frame its cloning into DNA vector produce plasmid pWRG/PUU-M(s2). pWRG/PUU-M(s2) delivered by gene gun produced high-titer...
We explored an emerging technology to produce anti-Hantaan virus (HTNV) and anti-Puumala (PUUV) neutralizing antibodies for use as pre- or post-exposure prophylactics. The involves hyperimmunization of transchomosomic bovines (TcB) engineered express human polyclonal IgG with HTNV PUUV DNA vaccines encoding GnGc glycoproteins. For the anti-HTNV product, TcB was hyperimmunized plus adjuvant formulated using lipid nanoparticles (LNP). LNP-formulated vaccine yielded fivefold higher antibody...
Hantaan virus (HTNV) and Puumala (PUUV) are rodent-borne hantaviruses that the primary causes of hemorrhagic fever with renal syndrome (HFRS) in Europe Asia. The development well characterized animal models HTNV PUUV infection is critical for evaluation potential licensure HFRS vaccines therapeutics. In this study we present three (hamster, ferret marmoset), two ferret). Infection hamsters a ~3 times infectious dose 99% (ID99) by intramuscular ~1 ID99 intranasal route leads to persistent...
Abstract Background Andes virus (ANDV), a rodent-borne hantavirus, causes hantavirus pulmonary syndrome (HPS). The safety and immunogenicity of novel ANDV DNA vaccine was evaluated. Methods Phase 1, double-blind, dose-escalation trial randomly assigned 48 healthy adults to placebo or delivered via needle-free jet injection. Cohorts 1 2 received mg in 3-dose (days 29, 169) 4-dose 57, schedule, respectively. 3 4 the Subjects were monitored for neutralizing antibodies by pseudovirion...
To combat the COVID-19 pandemic, an assortment of vaccines has been developed. Nucleic acid have advantage rapid production, as they only require a viral antigen sequence and can readily be modified to detected mutations. Doggybone™ DNA targeting spike protein SARS-CoV-2 generated compared with traditionally manufactured, bacterially derived plasmid vaccine that utilizes same sequence. Administered Syrian hamsters by jet injection at two dose levels, immunogenicity both was following...
ABSTRACT The emergence of SARS-CoV-2 has created an international health crisis. Small animal models mirroring human disease are essential for medical countermeasure (MCM) development. Mice refractory to infection due low affinity binding the murine angiotensin-converting enzyme 2 (ACE2) protein. Here we evaluated pathogenesis in male and female mice expressing ACE2 gene under control keratin 18 promotor. In contrast non-transgenic mice, intranasal exposure K18-hACE2 animals two different...
DNA vaccine evaluation in small animals is hampered by low immunogenicity when the vaccines are delivered using a needle and syringe. To overcome this technical hurdle we tested possibility that device developed for human intradermal medicine delivery might be adapted to successfully deliver animals. Disposable syringe jet injection (DSJI) does not currently exist However, commercialized, used administer medicines dermis 0.1 mL volume was evaluated Syrian hamsters. Here, found hantavirus...
ABSTRACT Hantaviruses are rodent-borne viruses that cause severe disease in infected humans. In the New World, major hantaviruses include Andes virus (ANDV) and Sin Nombre (SNV) causing hantavirus pulmonary syndrome. Old Hantaan (HTNV) Puumala (PUUV) hemorrhagic fever with renal Here, we produced a pan-hantavirus therapeutic (SAB-163) comprised of fully human immunoglobulin purified from plasma transchromosomic bovines (TcB) vaccinated DNA plasmids coding for glycoproteins ANDV, SNV, HTNV,...
Andes virus (ANDV) is associated with a lethal vascular leak syndrome in humans termed hantavirus pulmonary (HPS). The mechanism for the massive leakage HPS poorly understood; however, dysregulation of components immune response often suggested as possible cause. Alveolar macrophages are found alveoli lung and represent first line defense to many airborne pathogens. To determine whether alveolar play role pathogenesis, were depleted an adult rodent model that closely resembles human HPS....
This report is the first to demonstrate infection of human endothelial cells by Pichinde virus (PIC). PIC induces an upregulation inducible nitric oxide synthase gene; as well increase in detectable (NO). permeability cell monolayers which can be abrogated at all measured timepoints with addition a inhibitor, indicating role for NO alteration barrier function. Because has shown antiviral activity against some viruses, viral titer was after inhibitor and found have no effect altering load...
Sin Nombre virus (SNV) and Andes (ANDV) cause hantavirus pulmonary syndrome (HPS) in humans. Both SNV ANDV infect Syrian hamsters, but only causes lethal disease. A co-infection study was performed to determine which virus, or ANDV, would dominate the survival outcome hamsters. Infection of hamsters with 1 day before challenge did not result disease characteristic latter all animals survived challenge. Control infected solely succumbed by 14. In contrast, when viruses were injected at same...
Abstract Animal models recapitulating human COVID-19 disease, especially with severe are urgently needed to understand pathogenesis and evaluate candidate vaccines therapeutics. Here, we develop novel disease animal for involving disruption of adaptive immunity in Syrian hamsters. Cyclophosphamide (CyP) immunosuppressed or RAG2 knockout (KO) hamsters were exposed SARS-CoV-2 by the respiratory route. Both CyP-treated KO developed clinical signs that more than immunocompetent hamsters, notably...
Background Syrian hamsters infected with Andes virus (ANDV) develop a disease that recapitulates many of the salient features human hantavirus pulmonary syndrome (HPS), including lethality. Infection Hantaan (HTNV) results in an asymptomatic, disseminated infection. In order to explore this dichotomy, we examined transcriptome ANDV- and HTNV-infected hamsters. Results Using NanoString technology, kinetic transcriptional responses whole blood collected from Of 770 genes analyzed, key...