George Mason University

Other

George Mason Research Foundation, Inc.

Virongy L.l.c.

George Mason Intellectual Properties, Inc.

Yuntao Wu

Deemah Dabbagh

Yajing Fu

Zheng Zhou

Hong Shang

Mark Spear

Brian Hetrick

Sijia He

Rebecca Alyson Crook Yoder

Jeremy Kelly

Dongyang Yu

A major immune dysfunction persisting in chronic diseases such as HIV infection and cancer is the impairment of T cell motility and migration to tissues. Therapeutics such as antiretroviral therapy or cancer therapy frequently do not fully restore T cell motility for tissue migration and infiltration. Cofilin is an actin-depolymerizing factor that regulates actin dynamics for T cell migration. Here we demonstrate that the levels of cofilin phosphorylation in blood T cells (CD4 or CD8), macrophages, B cells, natural killer (NK) cells, and/or cancer cells can be used to quantify the immune damages caused by chronic viral infection and cancer, and to predict the recovery of T cells following treatment.

Cofilin phosphorylation for quantifying CD4 T cell damage and predict CD4 T cell recovery from anti-retroviral therapy

Embodiments relate to a method comprising (a) expressing a vector comprising a PSGL-1 (P-selectin glycoprotein ligand-1) or a mutant thereof in a VPC (virus producing cell); and blocking a virus infection by inactivating an infectivity of a released virions from the VPC; or (b) expressing a glycoprotein or a mutant thereof in the VPC; blocking the virus infection by preventing binding of the released virions to a target cell; inactivating infectivity of the released virions; and targeting a viral infection. Other embodiments relate to (1) a broad-spectrum anti-viral product comprising: a vector expressing a glycoprotein or a mutant thereof in a VPC; and blocking a virus infection by inactivating infectivity of a released virion from the VPC; and (2) a vaccine comprising a viral particle is configured to a live attenuated or an inactivated or a non-infectious, wherein the viral particle are produced in a VPC.

Method of inhibiting enveloped virus binding to target cells by incorporating P-selectin glycoprotein ligand-1 (PSGL-1) into virions

Recombinant viruses include one or more SHREK proteins and are thereby rendered non-infective and can be safely used in vaccines, e.g. to treat or prevent infections and to eliminate e.g. latent virus reservoirs.

Recombinant host cell with heterologous nucleic acids encoding SHREK proteins

Persistence of HIV in anatomic sanctuary sites such as the brain prevents viral eradication. Although combination antiretroviral therapy (cART) inhibits viral replication to undetectable level by standard clinical assay, it does not selectively eliminate virus reservoirs. To target HIV reservoirs, the present inventor developed an HIV Rev-dependent lentiviral vector carrying a series of therapeutic genes, such as diphtheria toxin, anthrolysin O from, human TRAF6, or the herpes simplex 1 virus thymidine kinase gene (HSV-tk). The present disclosure provides the Rev-dependent vectors for targeting viral reservoir in a SIV/rhesus macaque model. SIV-infected rhesus macaques were first treated with cART for over 6 months starting 12 weeks post infection, followed by injections with viral particles assembled from a SIV Rev-dependent vector carrying HSV-tk. Following particle injection, animals were further treated briefly (two weeks) with ganciclovir (GCV), which induces the killing of SIV+, HSV-tk expressing cells. cART was terminated following the GCV treatment, and there was observed a partial control of viral rebound over a period of 4 months after cART cessation. The animal was further treated with additional Rev-dependent vector particles, and viral load was diminished to the undetectable level for over 1 year in the absence of any treatment. These results suggest that the Rev-dependent vector, with or without a functional gene, has the potential to diminish viral reservoirs in vivo and can offer a cure of functional cure of HIV/SIV infection.

Rev-dependent lentiviral vaccine particles for reducing viral rebound and viral reservoirs in vivo

The present disclosure relates to composition and methodology for using the CD2 receptor to block viral replication, such as HIV-1 infection. In one embodiment, viral target cells such as blood CD4 T cells can be rendered resistant to HIV through stimulation of the CD2 receptor with either an antibody, a ligand, or a small molecule that binds to the CD2 receptor. Pre-stimulation of CD2 can be used to enhance the anti-HIV immunity and used to promote immune response from HIV infection or from an anti-HIV vaccine.

Compositions and methods for using the CD2-based signaling pathways to block HIV infection

Timely development of vaccines and antiviral drugs is critical to control the COVID-19 pandemic. Current methods for quantifying vaccine-induced neutralizing antibodies involve the use of pseudoviruses, such as the SARS-CoV-2 spike protein (S) pseudotyped lentivirus. However, these pseudoviruses contain structural proteins foreign to SARS-CoV-2, and require days to infect and express reporter genes. Here, the present application discloses composition and methodology for making and using a new hybrid alphavirus-SARS-CoV-2 (Ha-CoV-2) particle for rapid and accurate quantification of neutralization antibodies and viral variants.

Hybrid alphavirus-SARS-CoV-2 particle and methodology of making and using same

Embodiments relate to methods comprising expressing or overexpressing P-selectin glycoprotein ligand-1 (PSGL-1) in human immunodeficiency virus (HIV) producing cells; isolating HIV particles from the HIV producing cells; and preparing the isolated HIV particles as a HIV vaccine. Embodiments relate to systems comprising a HIV vaccine comprising live attenuated, inactivated, or non-infectious HIV particles. Embodiments relate to systems capable of performing a method comprising administering a vaccine comprising live attenuated, inactivated, or non-infectious HIV particles to a subject in need of the vaccine; and treating or preventing one or more disease states in the subject resulting from HIV infection. Embodiments relate to methods comprising expressing or overexpressing PSGL-1 in virus producing cells; and inhibiting viral infection; or inhibiting viral spreading; or inactivating viruses and virus producing cells; or producing non-infectious virion particles; or allowing the virus producing cells to produce non-infectious virions, isolating the virions, and preparing non-infectious virions, the virions being HIV particles.

Method and system for inactivating virus infectivity for producing live-attenuated vaccines

The present disclosure provides a method of restoring immune reconstitution, immune control of viremia, and one or more T cell functions in a subject infected with HIV. The method includes administering to the subject infected with HIV an agent that targets the cofilin pathway.

Targeting the cofilin pathway

Embodiments relate to expressing or overexpressing P-selectin glycoprotein ligand-1 (PSGL-1) in human immunodeficiency virus (HIV) producing cells; isolating HIV particles from the HIV producing cells; and preparing the isolated HIV particles as a HIV vaccine. Embodiments relate to a HIV vaccine comprising live attenuated, inactivated, or non-infectious HIV particles. Embodiments relate to systems performing a method comprising administering a vaccine comprising live attenuated, inactivated, or non-infectious HIV particles to a subject in need of the vaccine; and treating or preventing one or more disease states in the subject resulting from HIV infection. Embodiments relate to expressing or overexpressing PSGL-1 in virus producing cells; and inhibiting viral infection; or inhibiting viral spreading; or inactivating viruses and virus producing cells; or producing non-infectious virion particles; or allowing the virus producing cells to produce non-infectious virions, isolating the virions, and preparing non-infectious virions, the virions being HIV particles.

Compositions and methods for using actin-based peptides to modulate cellular bioactivity, including modulation of cellular susceptibility to intracellular pathogens, such as bacteria and viruses.

Compositions and methods for using actin-based peptides to modulate cellular bioactivity and cellular susceptibility to intracellular pathogens

In one aspect, the invention relates to methods and compositions for determining migration of a virus particle to the nucleus of a cell. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Methods and compositions for assessing viral nuclear localization

The present disclosure relates to the design of a retro- or lenti-viral HBV (hepatitis B virus) hybrid vector for delivery of HBV genomes into cells such as liver cells. Provided herein are design, methodology, compositions, and the like for such vectors for delivering HBV genes or genomes into cells for anti-HBV drug screening, HBV research, or test of anti-HBV therapeutics.

Retro- and lenti-HBV hybrid vectors and constructs

HIV infection can be detected by measuring phosphorylation levels of the actin-depolymerizing factor (AFD)/cofilin family, and infection can be treated and/or prevented by modulating the HIV co-receptor signaling pathway.

Growing community of inventors

Manassas, VA, United States of America

Yuntao Wu