The Government of the United States of America As Represented by the Secretary of the Deptartment of Health and Human Services

University of Michigan

Sanofi

United States of America, As Represented by the Secretary of the Navy

Dana-farber-cancer Institute Inc.

Genetics Institute, Inc.

University of Washington

Other

The Scripps Research Institute

Glaxosmithkline Biologicals Sa

Warner-lambert Company

Duke University

Janssen Vaccines & Prevention B.v.

Genvec, Inc.

US Government As Represented by the Secretary of the Army

Gary J Nabel

Zhi-yong Yang

Elizabeth G Nabel

Peter D Kwong

John R Mascola

Tongqing Zhou

Nancy J Sullivan

Carl H June

Gary S Gray

Paul David Rennert

Craig B Thompson

Wataru Akahata

Mark Connors

Xueling Wu

Ling Xu

Srinivas Rao

Zhi-Yong Yang

Chih-Jen Wei

Lan Wu

Ercole Rao

Richard Wyatt

Christian Beil

Jochen Beninga

Edward Seung

Bimal Chakrabarti

Baoshan Zhang

Yongping Yang

Ivelin Georgiev

Ronnie Rong Wei

Rebecca S Rudicell

Yue Huang

Kurt Swanson

Jiang Zhu

Christian Lange

Anthony Sanchez

Wulf Dirk Leuschner

Harvey I Cantor

Cheng Cheng

Béatrice Cameron

Tarik Dabdoubi

Cendrine Lemoine

William Ray Schief

Catherine Prades

Mario Roederer

Yuxing Li

Clement Asiedu

Carl-Magnus Hogerkorp

Joseph G Sodroski

Maria Grazia Pau

Stefano Colloca

Alfredo Nicosia

Masaru Kanekiyo

Riccardo Cortese

Jaap Goudsmit

Carsten Corvey

Young Do Kwon

Gwo-Yu Chuang

Wing-Pui Kong

Wei Shi

Gilad Ofek

Jinghe Huang

Barna Dey

Leo Laub

Wen Yuan

Shi-Hua Xiang

Zengguang Wang, Legal Representative

Manfred Boehm

Te-Hui Chou

Laura Nguyen

Dennis R Burton

Joerg Thomas Regula

Huawei Qiu

Wayne C Koff

Sanjay K Phogat

C Richter King

Jason G D Gall

Jochen Kruip

Jeffrey C Boyington

Jeffrey I Cohen

Pascal Raymond Georges Poignard

Hadi M Yassine

Virginia Ammendola

Thomas W Geisbert

Wei Bu

Joerg Birkenfeld

Peter B Jahrling

Annette Lynn Meyer

Leonard Post

Patrick M McTamney

Melissa Danielle De Jean St Marcel Simek-Lemos

Zhen Xing

Neil D Perkins

Roland M Schmid

Gordon James Freeman

Barton F Haynes

Pradeep K Dhal

John Mascola

Thomas B Kepler

Magda Marquet

The invention features compositions and methods for the prevention or treatment of one or more strains of Chikungunya virus, as well as other alphavirus-mediated diseases.

Chikungunya virus (CHIKV) virus-like particles (VLPS) comprising the C, E1, and E2 structural proteins

Provided herein are trispecific and/or trivalent binding proteins comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more target proteins, wherein a first pair of polypeptides forming the binding protein possess dual variable domains having a cross-over orientation, and wherein and a second pair of polypeptides possess a single variable domain forming a single antigen binding site. In some embodiments, the binding proteins comprise a binding site that binds a CD28 polypeptide, a binding site that binds a CD3 polypeptide, and a binding site that binds a third polypeptide, such as a tumor target protein. In some embodiments, the binding proteins comprise four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins. The disclosure also relates to methods for making trispecific and/or trivalent binding proteins and uses of such binding proteins.

Trispecific binding proteins, methods, and uses thereof

The invention features modified alphavirus or flavivirus virus-like particles (VLPs). The invention provides methods, compositions, and kits featuring the modified VLPs. The invention also features methods for enhancing production of modified VLPs for use in the prevention or treatment of alphavirus and flavivirus-mediated diseases. The invention also provides methods for delivering agents to a cell using the modified VLPs.

Virus-like particles and methods of use

This disclosure relates to antigenic EBV polypeptides and their use in eliciting antibodies against EBV. Also disclosed are antigenic polypeptides comprising an EBV polypeptide and a ferritin protein.

Antigenic Epstein Barr virus polypeptides

Antigenic respiratory syncytial virus (RSV) polypeptides for use in eliciting antibodies against RSV are provided. Also provided are antigenic polypeptides comprising an RSV polypeptide and a ferritin protein.

Antigenic respiratory syncytial virus polypeptides

Antigenic epstein barr virus polypeptides

Vaccines are provided that elicit neutralizing antibodies to Epstein-Barr virus (EBV). Some vaccines comprise nanoparticles that display envelope proteins from EBV on their surface. The nanoparticles comprise fusion proteins comprising a monomeric subunit of a self-assembly protein, such as ferritin, joined to at least a portion of an EBV envelope protein. The fusion proteins self-assemble to form the envelope protein-displaying nanoparticles. Such vaccines can be used to vaccinate an individual against infection by different types of Epstein-Barr viruses as well as Epstein-Barr viruses that are antigenically divergent from the virus from which the EBV envelope protein was obtained. Also provided are fusion proteins and nucleic acid molecules encoding such proteins.

Epstein-barr virus vaccines

This disclosure relates to antigenic OspA polypeptides and their use in eliciting antibodies against OspA. Also disclosed are antigenic polypeptides comprising an OspA polypeptide and a ferritin protein.

Antigenic OspA polypeptides

Method for producing chikungunya virus (CHIKV) virus-like particles comprising the C, E2, and E1 structural proteins

The disclosure provides trispecific and/or trivalent binding proteins comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more target proteins, wherein a first pair of polypeptides forming the binding protein possess dual variable domains having a cross-over orientation and wherein a second pair of polypeptides forming the binding protein possess a single variable domain. The disclosure also provides methods for making trispecific and/or trivalent binding proteins and uses of such binding proteins.

Trispecific and/or trivalent binding proteins

This invention provides vaccines for inducing an immune response and protection against filovirus infection for use as a preventative vaccine in humans. In particular, the invention provides chimpanzee adenoviral vectors expressing filovirus proteins from different strains of Ebolavirus (EBOV) or Marburg virus (MARV).

Chimpanzee adenoviral vector-based filovirus vaccines

Ferritin proteins comprising a mutation replacing a surface-exposed amino acid with a cysteine, an N- or C-terminal linker comprising a cysteine, and/or one or more immune-stimulatory moieties linked to the ferritin protein via a surface-exposed amino acid are disclosed. The ferritin proteins can further comprise a non-ferritin polypeptide and be antigenic, e.g., for use in eliciting antibodies against the non-ferritin polypeptide.

Ferritin proteins

Provided herein are bivalent, bispecific binding proteins that specifically bind to two different HIV-1 Env protein epitopes.

Bivalent, bispecific binding proteins for prevention or treatment of HIV infection

Growing community of inventors

Washington, DC, United States of America

Gary J Nabel