A5091274192- Mosquito-borne diseases and control
- Viral Infections and Vectors
- Viral Infections and Outbreaks Research
- Viral gastroenteritis research and epidemiology
- HIV Research and Treatment
- SARS-CoV-2 and COVID-19 Research
- Virology and Viral Diseases
- Bacteriophages and microbial interactions
- Herpesvirus Infections and Treatments
- Respiratory viral infections research
- Hepatitis B Virus Studies
- Plant Virus Research Studies
- Animal Virus Infections Studies
- Bacillus and Francisella bacterial research
- Disaster Response and Management
- Cytomegalovirus and herpesvirus research
- Yersinia bacterium, plague, ectoparasites research
- Viral Infections and Immunology Research
- interferon and immune responses
- Vibrio bacteria research studies
- Chemical Safety and Risk Management
- Virus-based gene therapy research
- Leptospirosis research and findings
- Diverse Research and Applications
- Studies on Chitinases and Chitosanases
United States Army Medical Research Institute of Infectious Diseases
2016-2025
United States Department of the Army
2008-2012
Baylor College of Medicine
2000-2003
Outbreaks of emerging infections present health professionals with the unique challenge trying to select appropriate pharmacologic treatments in clinic little time available for drug testing and development. Typically, clinicians are left general supportive care often untested convalescent-phase plasma as treatment options. Repurposing approved pharmaceutical drugs new indications presents an attractive alternative clinicians, researchers, public agencies, developers, funding agencies. Given...
Several FDA-approved drugs, including bepridil and sertraline, may be therapeutics against filovirus infections.
Profiling the antibody response to Ebola The recent virus outbreak in West Africa illustrates need not only for a vaccine but potential therapies, too. One promising therapy is monoclonal antibodies that target Ebola's membrane-anchored glycoprotein (GP). Bornholdt et al. isolated and characterized 349 from survivor of 2014 outbreak. A large fraction showed some neutralizing activity several were quite potent. Structural analysis revealed an important site vulnerability on membrane stalk...
Ebola virus (EBOV) remains a public health threat. We performed longitudinal study of B cell responses to EBOV in four survivors the 2014 West African outbreak. Infection induced lasting EBOV-specific immunoglobulin G (IgG) antibodies, but their subclass composition changed over time, with IgG1 persisting, IgG3 rapidly declining, and IgG4 appearing late. Striking changes occurred repertoire, massive recruitment naive cells that subsequently underwent hypermutation. characterized large panel...
ABSTRACT Norwalk virus (NV) is a causative agent of acute epidemic nonbacterial gastroenteritis in humans. The inability to cultivate NV has required the use molecular techniques examine genome organization and functions viral proteins. function protein encoded by open reading frame 3 (ORF 3) been unknown. In this paper, we report characterization ORF expressed cell-free translation system insect cells show its association with recombinant virus-like particles (VLPs) virions. Expression...
ABSTRACT The unprecedented 2014-2015 Ebola virus disease (EVD) outbreak in West Africa has highlighted the need for effective therapeutics against filoviruses. Monoclonal antibody (MAb) cocktails have shown great potential as EVD therapeutics; however, existing protective MAbs are species specific. Here we report development of pan-ebolavirus and pan-filovirus antibodies generated by repeated immunization mice with filovirus glycoproteins engineered to drive B cell responses toward conserved...
Several ebolaviruses cause outbreaks of severe disease. Vaccines and monoclonal antibody cocktails are available to treat Ebola virus (EBOV) infections, but not Sudan (SUDV) or other ebolaviruses. Current contain antibodies that cross-react with the secreted soluble glycoprotein (sGP) absorbs virus-neutralizing antibodies. By sorting memory B cells from EBOV infection survivors, we isolated two broadly reactive anti-GP antibodies, 1C3 1C11, potently neutralize, protect rodents disease, lack...
Eastern and Venezuelan equine encephalitis viruses (EEEV VEEV, respectively) cause severe morbidity mortality in equines humans. Like other mosquito-borne viruses, VEEV infects dendritic cells (DCs) macrophages lymphoid tissues, fueling a serum viremia facilitating neuroinvasion. In contrast, EEEV replicates poorly preferentially infecting osteoblasts. Here, we demonstrate that infectivity of for myeloid lineage including DCs was dramatically reduced compared to whereas both replicated...
ABSTRACT Filoviruses cause highly lethal viral hemorrhagic fever in humans and nonhuman primates. Current immunotherapeutic options for filoviruses are mostly specific to Ebola virus (EBOV), although other members of Filoviridae such as Sudan (SUDV), Bundibugyo (BDBV), Marburg (MARV) have also caused sizeable human outbreaks. Here we report a set pan-ebolavirus pan-filovirus monoclonal antibodies (MAbs) derived from cynomolgus macaques immunized repeatedly with mixture engineered...
Western, Eastern, and Venezuelan equine encephalitis viruses (WEEV, EEEV, VEEV, respectively) are important mosquito-borne agents that pose public health bioterrorism threats. Despite considerable advances in understanding alphavirus replication, there currently no available effective vaccines or antiviral treatments against these highly lethal pathogens. To develop a potential countermeasure for viral encephalitis, we generated trivalent, three-component, EEV vaccine composed of virus-like...
Eastern equine encephalitis virus (EEEV), an arbovirus, is important human and veterinary pathogen belonging to one of seven antigenic complexes in the genus Alphavirus, family Togaviridae. EEEV considered most deadly mosquito-borne alphaviruses due high case fatality rate associated with clinical infections, reaching up 75 % humans 90 horses. In patients that survive acute infection, neurologic sequelae are often devastating. Although natural infections acquired by mosquito bite, also...
Background.A need to develop therapeutics treat Ebola virus disease patients in remote and resource-challenged settings remains the wake of 2013-2016 epidemic West Africa.Toward this goal, we screened drugs under consideration as treatment options other interest, most being small molecules approved by Food Drug Administration.Drugs demonstrating vitro antiviral activity were advanced for evaluation combinations because advantages often provided drug cocktails.Methods.Drugs blockade infection...
Significance In recent years, systematic research efforts have led to the preclinical development of antibody-based therapeutics that confer potent antiviral activity against Ebola virus (EBOV). Immunoglobulin G (IgG) antibodies pathogens depend on their interaction with specialized leukocyte receptors (Fcγ [FcγRs]) functions. FcγR engagement by IgG induces activation and mediates pleiotropic effector functions control infection. Here, we examined contribution antibody-mediated protection...
Neglected diseases caused by arenaviruses such as Lassa virus (LASV) and filoviruses like Ebola (EBOV) primarily afflict resource-limited countries, where antiviral drug development is often minimal. Previous studies have shown that many approved drugs developed for other clinical indications inhibit EBOV LASV combinations of these provide synergistic suppression EBOV, blocking discrete steps in entry. We hypothesize repurposing orally administered provides effective arenaviruses. In this...
SummaryBackgroundImmune responses to alphavirus vaccines might be impaired when heterologous are administered sequentially. We aimed compare immunogenicity and safety of a chikungunya virus virus-like particle (CHIKV VLP) vaccine in previous recipients with alphavirus-naive controls the USA.MethodsIn this open-label, parallel-group, age-matched, sex-matched, phase 2 randomised controlled trial, which was conducted at two clinical study sites USA, adults (aged 18–65 years) who had previously...
Alphavirus replicons were evaluated as potential vaccine candidates for Venezuelan equine encephalitis virus (VEEV), western (WEEV), or eastern (EEEV) when given individually in combination (V/W/E) to mice cynomolgus macaques. Individual replicon vaccines the V/W/E elicited strong neutralizing antibodies their respective alphavirus. Protection from either subcutaneous aerosol challenge with VEEV, WEEV, EEEV was demonstrated out 12 months after vaccination mice. macaques and good protection...
The Venezuelan equine encephalitis virus (VEEV) nonstructural protein 2 (nsP2) cysteine protease (EC 3.4.22.-) is essential for viral replication and involved in the cytopathic effects (CPE) of virus. VEEV nsP2 a member MEROPS Clan CN characteristically contains papain-like linked to an S-adenosyl-l-methionine-dependent RNA methyltransferase (SAM MTase) domain. alternative active site motif, (475)NVCWAK(480), which differs from papain's (CGS(25)CWAFS), enzyme lacks transition...
Eastern equine encephalitis virus (EEEV) is an alphavirus with a case fatality rate estimated to be as high 75 % in humans and 90 horses. Surviving patients often have long-lasting severe neurological sequelae. At present, there no licensed vaccine or therapeutic for EEEV infection. This study completes the clinical pathological analysis of mice infected North American strain by three different routes: aerosol, intranasal, subcutaneous. Such understanding imperative use mouse model antiviral...
In the fall of 2014, an international news agency reported that patients suffering from Ebola virus disease (EVD) in Liberia were treated successfully with lamivudine, antiviral drug used to treat human immunodeficiency virus-1 and hepatitis B infections. According report, 13 out 15 lamivudine survived declared free disease. this study, anti-Ebola (EBOV) activity another antiretroviral, zidovudine, evaluated a diverse set cell lines against two variants wild-type EBOV. Variable assay...
Western equine encephalitis virus (WEEV) causes symptoms in humans ranging from mild febrile illness to life-threatening encephalitis, and no human medical countermeasures are licensed. A previous study demonstrated that immune serum vaccinated mice protected against lethal WEEV infection, suggesting the utility of antibodies for pre- post-exposure treatment. Here, three neutralizing one binding human-like monoclonal were evaluated aerosol challenge. Dose-dependent protection was observed...
There are no FDA licensed vaccines or therapeutics for Venezuelan equine encephalitis virus (VEEV) which causes a debilitating acute febrile illness in humans that can progress to encephalitis. Previous studies demonstrated murine and macaque monoclonal antibodies (mAbs) provide prophylactic therapeutic efficacy against VEEV peripheral aerosol challenge mice. Additionally, humanized versions of two neutralizing mAbs specific the E2 glycoprotein, 1A3B-7 1A4A-1, administered singly protected...