A5048815943- Viral Infections and Vectors
- Viral Infections and Outbreaks Research
- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- Mosquito-borne diseases and control
- Fire effects on ecosystems
- Cancer Research and Treatments
- Immunotherapy and Immune Responses
- Viral Infectious Diseases and Gene Expression in Insects
- Vector-Borne Animal Diseases
- Viral gastroenteritis research and epidemiology
- Herpesvirus Infections and Treatments
- Cytomegalovirus and herpesvirus research
Albert Einstein College of Medicine
2018-2023
Metis Design Corporation (United States)
2011-2015
The rodent-borne hantavirus Puumala virus (PUUV) and related agents cause hemorrhagic fever with renal syndrome (HFRS) in humans. Other hantaviruses, including Andes (ANDV) Sin Nombre virus, a distinct zoonotic disease, cardiopulmonary (HCPS). Although these infections are severe have substantial case fatality rates, no FDA-approved countermeasures available. Recent work suggests that monoclonal antibodies may therapeutic utility. We describe here the isolation of human neutralizing (nAbs)...
Emerging rodent-borne hantaviruses cause severe diseases in humans with no approved vaccines or therapeutics. We recently isolated a monoclonal broadly neutralizing antibody (nAb) from Puumala virus–experienced human donor. Here, we report its structure bound to target, the Gn/Gc glycoprotein heterodimer comprising viral fusion complex. The explains broad activity of nAb: It recognizes conserved Gc loop sequences and main chain variable Gn sequences, thereby straddling locking it prefusion...
Rodent-to-human transmission of hantaviruses is associated with severe disease. Currently, no FDA-approved, specific antivirals or vaccines are available, and the requirement for high biocontainment (biosafety level 3 [BSL-3]) laboratories limits hantavirus research. To study entry in a BSL-2 laboratory, we set out to generate replication-competent, recombinant vesicular stomatitis viruses (rVSVs) bearing Gn Gc (Gn/Gc) glycoproteins. As previously reported, rVSVs New World Gn/Gc were readily...
We have engineered an integration-deficient lentiviral vector, LV305, to deliver the tumor antigen NY-ESO-1 human dendritic cells in vivo through pseudotyping with a modified Sindbis virus envelop protein. Mice immunized once LV305 developed strong, dose-dependent, multifunctional, and cytotoxic NY-ESO-1-specific cluster of differentiation 8 (CD8) T within 14 days post-immunization could be boosted at least twice recall peak-level CD8 T-cell responses. Immunization protected mice against...
As sentinels of the immune system, dendritic cells (DCs) play an essential role in regulating cellular responses. One main challenges developing DC-targeted therapies includes delivery antigen to DCs order promote activation antigen-specific effector CD8 T cells. With goal creating antigen-directed immunotherapeutics that can be safely administered directly patients, Immune Design has developed a platform novel integration-deficient lentiviral vectors target and deliver antigen-encoding...
Andes virus (ANDV) and Sin Nombre (SNV) are the main causative agents responsible for hantavirus cardiopulmonary syndrome (HCPS) in Americas. HCPS is a severe respiratory disease with high fatality rate which there no approved therapeutics or vaccines available. Some vaccine approaches have been tested preclinical models, but none infectious models regard to their ability protect against multiple species of HCPS-causing viruses. Here, we utilize recombinant vesicular stomatitis virus-based...
Dendritic cells (DCs) are essential antigen-presenting for the initiation of cytotoxic T-cell responses and therefore attractive targets cancer immunotherapy. We have developed an integration-deficient lentiviral vector termed ID-VP02 that is designed to deliver antigen-encoding nucleic acids selectively human DCs in vivo. utilizes a genetically glycobiologically engineered Sindbis virus glycoprotein target through C-type lectin DC-SIGN (CD209) also binds homologue murine receptor SIGNR1....
Multiple agents in the family Filoviridae (filoviruses) are associated with sporadic human outbreaks of highly lethal disease, while others, including several recently identified agents, possess strong zoonotic potential. Although viral glycoprotein (GP)-specific monoclonal antibodies have demonstrated therapeutic utility against filovirus currently FDA-approved molecules lack antiviral breadth. The development broadly neutralizing has been challenged by high sequence divergence among GPs...
Abstract Andes virus (ANDV) and Sin Nombre (SNV) are the etiologic agents of severe hantavirus cardiopulmonary syndrome (HCPS) in Americas for which no FDA-approved countermeasures available. Protocadherin-1 (PCDH1), a cadherin-superfamily protein recently identified as critical host factor ANDV SNV, represents new antiviral target; however, its precise role remains to be elucidated. Here, we use computational experimental approaches delineate binding surface glycoprotein complex on PCDH1’s...
Lentiviral vectors (LVs) are being developed for clinical use in humans applications including gene therapy and immunotherapy. A safety concern of LVs is the generation replication-competent lentivirus (RCL), which may arise due to recombination between split genomes third-generation LVs. Although no RCL has been detected date, design optimizations that minimize events genome would provide an added benefit further reduce risk formation. Here we describe elements introduced gag/pol plasmid...
Using lentiviral vector products in clinical applications requires an accurate method for measuring transduction titer. For vectors lacking a marker gene, quantitative polymerase chain reaction is used to evaluate the number of DNA copies transduced target cells, from which titer calculated. Immune Design previously described integration-deficient pseudotyped with modified Sindbis virus envelope use cancer immunotherapy (VP02, ZVex platform). Standard protocols titering integration-competent...
Abstract With the goal of creating antigen-directed immunotherapeutics that can be safely administered directly to patients, Immune Design has developed a platform novel integration-deficient lentiviral vectors target and deliver antigen-encoding nucleic acids dendritic cells (DCs) in order promote activation antigen-specific effector CD8 T cells. This platform, termed DCVex(TM), utilizes genetic variant Sindbis virus envelope glycoprotein with post-translational carbohydrate modifications...
Abstract Rodent-to-human transmission of hantaviruses is associated with severe disease. Currently, no FDA-approved, specific antivirals or vaccines are available, and the requirement for high biocontainment (BSL3) laboratories limits hantavirus research. To study entry in a BSL-2 laboratory, we set out to generate replication-competent, recombinant vesicular stomatitis viruses (rVSVs) bearing Gn/Gc glycoproteins. As previously reported, rVSVs New World were readily rescued from cDNAs, but...
Hantaviruses are found throughout the world and can cause deadly diseases in humans, specifically, hantavirus cardiopulmonary syndrome (HCPS) New World hemorrhagic fever with renal (HFRS) Old World. Currently, no FDA-approved, specific antiviral drugs or vaccines available. Recently, we showed that hantaviruses utilize protocadherin-1 (PCDH1) for endothelial cell entry infection by directly engaging its first extracellular cadherin repeat (EC1) domain. The knockout of PCDH1 also greatly...
Abstract Andes virus and Sin Nombre are the etiologic agents of severe hantavirus cardiopulmonary syndrome (HCPS) in Americas for which no FDA-approved countermeasures available. Protocadherin-1 (PCDH1), a cadherin-superfamily protein recently identified as critical host factor ANDV SNV, represents new antiviral target; however, its precise role remains to be elucidated. Here, we used computational experimental approaches delineate binding surface glycoprotein complex on PCDH1’s first...