Yale University

John K Rose

Matthias Johannes Schnell

Nina Rose

Michael Robek

Tracy Reynolds

E Erik Johnson

The present invention relates to the discovery of a high titer hybrid-virus vector that gives rise to high titer virus like vesicles (VLVs) that can be used as a vaccine. The invention includes compositions and methods of generating an evolved hybrid-virus vector vaccine and selecting high titer VLVs, methods of treating and/or preventing or immunizing against, a specific disease or disorder, and methods of inducing a memory T cell and B cell immune response in a subject administered the VLV composition produced thereby. Furthermore, the invention encompasses a pharmaceutical composition for vaccinating a subject as well as a high titer protein expression system.

Evolution of high-titer virus-like vesicles for vaccine applications

The present invention relates to the discovery of compositions and methods for therapeutic immunization for treatment of chronic hepatitis B. Methods of the invention include a method generating an evolved high titer hybrid-hepatitis B virus (HBV) vector, methods of treating and/or preventing HBV, and methods of inducing a memory T and B cell immune response against HBV infection in a subject administered the VLV composition produced thereby. Furthermore, the invention encompasses a pharmaceutical composition for vaccinating a subject to protect the subject against infection with HBV.

Virus like vesicles (VLVS) based vaccines to prevent or treat chronic hepatitis B virus (HBV) infection

The invention provides recombinant replicable vesiculoviruses. The invention provides a method which, for the first time, successfully allows the production and recovery of replicable vesiculoviruses, as well as recombinant replicable vesiculoviruses, from cloned DNA, by a method comprising expression of the full-length positive-strand vesiculovirus antigenomic RNA in host cells. The recombinant vesiculoviruses do not cause serious pathology in humans, can be obtained in high titers, and have use as vaccines. The recombinant vesiculoviruses can also be inactivated for use as killed vaccines.

Recombinant vesiculoviruses and their uses

Replication-competent recombinant rhabdoviruses that lack a functional glycoprotein gene and express at least one foreign polypeptide such as a celluar receptor for another virus in their viral envelopes are useful in the treatment of pathogenic viruses. In one embodiment, a recombinant vesicular stomatitis virus (VSV) lacking its glycoprotein (G) gene and expressing instead the HIV receptor and a coreceptor is employed in a method for treating persons infected with HIV. The recombinant virus is defective for entry into normal cells but is able to control HIV infection in a T cell line by replicating in, and killing, HIV-infected cells.

Rhabdoviruses with reengineered coats

Methods for making modified recombinant vesiculoviruses

A reagent for introducing a nucleic acid into an animal cell. The reagent comprises (a) a neutral lipid such as dioleoylphosphatidylethanolamine and (b) a cationic lipid selected from the group consisting of an ammonium salt such as dimethyldioctadecylammonium bromide or cetyldimethylethylammonium bromide, an amine such as stearylamine, and a benzethonium salt such as methylbenzethonium chloride

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Guilford, CT, United States of America

John K Rose