The founding of the VGTI was based on the increasing realization that progress in these areas of investigation requires high level expertise and experience in virology, immunology, animal models, pathology and clinical infectious disease, a combination that is rarely found in a single investigator. The strategy of the VGTI is to provide a close-knit collaborative environment for a group of independent scientists within these disciplines that could interact on a daily basis.
In 2001 the VGTI Building was designed to include 4 BSL3 labs, 2 rodent and 2 NHP ABSL3 facilities to handle highly pathogenic pathogens. These are the only containment facilities at OHSU capable of handling COVID19. It is very fortunate we have these facilities which are the only ones in Oregon that will allow us to study this virus to make vaccines and antivirals. All COVID19 research with viral infections will occur at the VGTI.
From 2009-2014 Jay Nelson was the Director of the NIAID Pacific Northwest Research Centers of Excellence (PNWRCE) in Biodefense and Emerging Infectious Diseases, a consortium of investigators from 20 institutions with extensive expertise and basic and translational research capacity directed at a broad range of NIAID Category A–C Priority Pathogens including Influenza, Ebola, SARS, Dengue, and Chikungunya viruses. The goal of the PNWRCE is to identify age-related immune system defects to develop new vaccines and supplemental therapies to enhance protection of individuals. This center positioned the VGTI as one of the best groups in the world to develop vaccines and therapies for emerging disease.
In 2014 the PNWRCE transitioned into the Centers of Excellence in Translational Research (CETRs) that were centers to accelerate the development of vaccines and therapeutics in emerging diseases. Several groups at the VGTI are part of this research effort. Our focus has been on Dengue Zika and Chikungunya while others in our group are studying SARS and COVID19. We have been working with Gilead and that group was involved in the identification one of the drugs Gilead is testing today.
COVID19 Vaccine Development
The use of CMV as a Vaccine Vector for COVID19. Drs. Klaus, Louis, and Meaghan Hancock.
This project will use CMV as a vector for COVID19 to determine whether induction of T cell or B cell immunity or both are needed for immune protection. Since Coronaviruses are notorious for vaccine enhancement of disease, this project will also examine whether the enhancement is triggered by the Tor B cell response.
The use of Gamma herpesviruses as a Vaccine Vector for COVID19. Dr. Scott Wong.
This project will test whether gamma herpesvirus can be used as a vaccine vector for COVID19.
Identification of Vaccine adjuvants for COVID19. Drs. Victor DeFilippis and Alec Hirsch.
This project will use various vaccine adjuvants being developed at the VGTI can be used with noninfectious virus like COVID19 particles as an effective vaccine. As stated above Coronaviruses vaccines can enhance disease so this project will use vaccine adjuvants to mold the immune response so that it is protective but doesn’t accelerate disease.
The use of Neutralizing antibodies to CCR5 as an intervention to COVID19 induced pneumonia. Dr. Jonah Sacha.
This project in collaboration with a company will test whether neutralizing antibodies to CCR5 a receptor on macrophages can block the inflammatory process causing the pneumonia in COVID19 patients. He will be testing this in NHPs.
Drs. Louis Picker and Scott Hansen will be working with Dr. Marcel Curlin to test whether the SARS-CoV2-specific T cell response can be used as an early diagnostic marker of COVID19 infection, a predictor of outcome, or a reliable indicator of past infection and immunity.
Dr. Meaghan Hancock is working with Drs. Dan Streblow and Donna Hansel to develop a new antibody test that is specific for COVID19. The current tests are not specific and cross react with other Coronavirus infections that represent 15% of all common colds.
The establishment of the COVID19 clinical testing lab with Donna Hansel. Dan Streblow and Alec Hirsch have been in the lab since its inception to make sure that tests are running smoothly.
Lastly, VIR Biotechnologies that spun out of the VGTI is currently in clinical trials testing humanized antibodies to COVID19 as an antiviral therapy.
|PI||Title||Focus 1||Focus 2|
|Frueh, Klaus||Long-term Coronavirus Immunity||Prevention of SARC-CoV2 infections|
|Streblow, Daniel||Immunogenicity testing of novel DC targeting, non-replicating Adenovirus vectors against nCOVID-19 in mice and rhesus macaques.||Prevention of SARC-CoV2 infections|
|Hansen, Scott||To develop intracellular cytokine staining (ICS) assays to identify SARS CoV-2 antigen-specific T cell responses in individuals infected or potentially infected with COVID-19 using PBMC. If successful an assay such as this could increase screening capacity to ~1000 individuals per day.||Development of Diagnostic testing for COVID-19 Pts.||Based science of SARS-CoV2|
|DeFilippis, Victor||The goal of the work is to characterize replication-incompetent virus like particles and viral protein subunits in combination with novel and established adjuvants as prophylactic vaccines against SARS-CoV-2. This will be done in mice and nonhuman primates and include readouts of elicited humoral and cell-mediated immunity.||Prevention of SARC-CoV2 infections|
|Estes, Jacob||Defining the early histopathology and viral dynamics in tissues in SARS-CoV2 infected NHPs||Based science of SARS-CoV2|
|Hirsch, Alec||The goal of this project is to develop and characterize SARS-CoV-2 virus-like particles (VLPs). We will use a well-established protocol to express the viral structural proteins (E, M, N, and S) in mammalian cells and purify VLPs for the purpose of injecting into mice and nonhuman primates (NHPs). Immune responses induced by injection of SARS-CoV-2 VLPs with a range of adjuvants and adjuvant combinations will be characterized by ELISA and T cell assays. This research will contribute to our understanding of immunity to SARS-CoV-2 infections and aid in the future development of vaccines targeting this and other coronaviruses. We will coordinate with other labs at the VGTI that are pursuing similar strategies to develop optimal expression systems for VLP development and avoid overlap.||Prevention of SARC-CoV2 infections||Based science of SARS-CoV2|
|Wong, Scott||Comparing the immunogenicity of gamma-herpesvirus vectors and poxvirus vectors expressing the spike (S) protein of COVID19.||Prevention of SARC-CoV2 infections|
|Moses, Ashlee||Working Title: Chitosan-based Biopolymers to Prevent the Spread of SARS-CoV-2 (COVID-19) Brief Statement of Research: The overall goal is to develop an N95 respirator mask with improved efficacy in preventing the spread of COVID-19 in respiratory droplets and aerosols. The modification involves replacement of the standard N95 filter unit with a chitosan-based glucosamine biopolymer mesh in order to leverage the established anti-microbial and physical-trapping properties of chitosan against COVID-19.||Prevention of SARC-CoV2 infections|
|Burwitz, Ben||We will generate and produce a replication-deficient SARS-CoV2 reporter virus and establish a high-throughput platform for drug and antibody screenings.||Development of Diagnostic testing for COVID-19 Pts.||TX of COVID-19 pts Based science of SARS-CoV2|
|Sacha, Jonah||We will test the ability of the CCR5-blocking monoclonal antibody, Leronlimab, to block the influx of inflammatory cells into the lungs of SARS-CoV2-infected rhesus macaques. All work will occur at the Tulane National Primate Research Center in their level 3 laboratory.||TX of COVID-19 pts|
|Hancock, Meaghan||Prospective Cohort:We will develop an ELISA assay utilizing a novel fusion of SARS-CoV2 Spike domains for potential clinical and research applications.||Development of Diagnostic testing for COVID-19 Pts.||Based science of SARS-CoV2|
|Hirsch, Alec||Retrospective Cohort: COVID-19 Projects Requiring BSL3-Containment||Development of Diagnostic testing for COVID-19 Pts.||TX of COVID-19 pts|