University of Washington

University of Utah Research Foundation

Institute for Research in Biomedicine

The Scripps Research Institute

International Aids Vaccine Initiative

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Fred Hutchinson Cancer Center

Neil P King

David Baker

Daniel Ellis

Jacob Bale

William H Sheffler

Lance Joseph Stewart

Antonio Lanzavecchia

Marc J Lajoie

Jorge Fallas

Wesley Sundquist

Daniel Stetson

Jessica Marcandalli

Yang Hsia

Brooke Fiala

Laurent Perez

Elizabeth Gray

William Ray Schief

George Ueda

Sergey V Menis

Joseph Graham Jardine

Po-Ssu Huang

Joerg Votteler

Gabriel Butterfield

Barney S Graham

Masaru Kanekiyo

Todd O Yeates

Lauren Carter

Jesse Bloom

Allison Greaney

Katherine DaPron

Jing Yang Wang

Tyler Starr

Seyhan Boyoglu-Barnum

Rebecca A Gillespie

Jörg Philip Votteler

Brooke Nickerson

Rashmi Ravichandran

Una Nattermann

Nanoparticles and vaccines containing these nanoparticles that elicit an immune response against hemagglutinin (HA) proteins from a broad range of influenza viruses are provided. The nanoparticles are made from self-assembling proteins, at least one of which is joined to an immunogenic portion of an influenza HA protein. This immunogenic portion is displayed on the nanoparticle surface, making the nanoparticles useful for vaccinating subjects against influenza virus.

Nanoparticle-based influenza virus vaccines and uses thereof

Disclosed herein are modified capsid proteins comprising a capsid forming protein, a membrane binding element and an ESCRT-recruiting element, wherein at least one of the membrane binding element and the ESCRT-recruiting element is heterologous to the capsid forming protein. Disclosed are capsids comprising a plurality of modified capsid proteins. Disclosed are multimeric assemblies comprising a plurality of capsids within a membrane. Also disclosed are modified non-enveloped viruses comprising a capsid wherein the capsid comprises a plurality of modified capsid proteins, wherein the plurality of modified capsid proteins comprise a capsid forming protein, a membrane binding element and an ESCRT-recruiting element, wherein at least one of the membrane binding element and the ESCRT-recruiting element is heterologous to the modified capsid protein, wherein the capsid forming protein is a capsid forming protein of a non-enveloped virus.

Engineering virus-like nanocarriers for biomolecule delivery

Disclosed herein are nanostructures and their use, where the nanostructures include

Self-assembling protein nanostructures displaying paramyxovirus and/or pneumovirus F proteins and their use

Provided herein are compositions and methods comprising mutated coronavirus 'S' spike proteins or receptor binding domains thereof that have an increased expression level, yield and stability compared to its corresponding native or wild-type coronavirus spike protein under the same expression, culture or storage conditions. These mutated spike proteins can be used for generating a protein-based vaccine against one or more coronaviruses.

Stable coronavirus proteins and vaccine compositions thereof

The application discloses multimeric assemblies packaging one or more active component and their use to carry out nucleic acid regulation or gene editing.

Genome editing reagents and their use

Nanostructures and nanostructure-based vaccines that display antigens capable of eliciting immune responses to infectious agents such as bacteria, viruses, and pathogens are provided. Some vaccines are useful for preventing or decreasing the severity of infection with an infectious agent, including, for example and without limitation, lyme disease, pertussis, herpes virus, orthomyxovirus, paramyxovirus, pneumovirus, filovirus, flavivirus, reovirus, retrovirus, meningococcus, or malaria. The antigens may be attached to the core of the nanostructure either non-covalently or covalently, including as a fusion protein or by other means. Multimeric antigens may optionally be displayed along a symmetry axis of the nanostructure. Also provided are proteins and nucleic acid molecules encoding such proteins, vaccine compositions, and methods of administration.

Self-asssembling nanostructure vaccines

Disclosed herein are nanostructures and their use, where the nanostructures include (a) a plurality of first assemblies, each first assembly comprising a plurality of identical first polypeptides; (b) a plurality of second assemblies, each second assembly comprising a plurality of identical second polypeptides, wherein the second polypeptide differs from the first polypeptide; wherein the plurality of first assemblies non-covalently interact with the plurality of second assemblies to form a nanostructures; and wherein the nanostructure displays multiple copies of one or more paramyxovirus and/or pneumovirus F proteins or antigenic fragments thereof, on an exterior of the nanostructure.

Synthetic nanostructures, polypeptides that are useful, for example, in making synthetic nanostructures, and methods for using such synthetic nanostructures are disclosed herein.

Polypeptides for use in self-assembling protein nanostructures

The application discloses multimeric assemblies including multiple oligomeric substructures, where each oligomeric substructure includes multiple proteins that self-interact around at least one axis of rotational symmetry, where each protein includes one or more polypeptide-polypeptide interface ('O interface'); and one or more polypeptide domain that is capable of effecting membrane scission and release of an enveloped multimeric assembly from a cell by recruiting the ESCRT machinery to the site of budding by binding to one or more proteins in the eukaryotic ESCRT complex ('L domain'); and where the multimeric assembly includes one or more subunits comprising one or more polypeptide domain that is capable of interacting with a lipid bilayer (&#x201c;M domain&#x201d;), as well as membrane-enveloped versions of the multimeric assemblies.

Polypeptide assemblies and methods for the production thereof

The invention relates to an engineered outer domain (eOD) of HIV gp120 and mutants thereof and methods of making and using the same. The mutant eODs may be advantageous for the elicitation of CD4-binding site (CD4bs)-directed broadly-neutralizing antibodies (bnAbs) and/or improve binding to mature VRC01 and/or improve binding to germline VRC01 and the germlines of other VH1-2 derived broadly-neutralizing antibodies. The mutant eODs may also include glycan-masking mutations on eOD. The present invention also includes fusions of eOD to various protein multimers to enhance immunogenicity as well as the design of cocktails of different eODs that represent the full diversity of HIV sequences within the VRC01 epitope and surroundings.

Engineered outer domain (EOD) of HIV GP120 and mutants thereof

Synthetic nanostructures, proteins that are useful, for example, in making synthetic nanostructures, and methods for designing such synthetic nanostructures are disclosed herein.

Self-assembling protein nanostructures

Engineered outer domain (eOD) of HIV gp120 and mutants thereof

Growing community of inventors

Seattle, WA, United States of America

Neil P King