National Institutes of Health, a Component of the US Dept. of Health & Human Services

The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc.

The Scripps Research Institute

Dartmouth College

University of Washington

Masaru Kanekiyo

Barney S Graham

Michael Gordon Joyce

Jeffrey C Boyington

Hadi M Yassine

John R Mascola

Peter D Kwong

Jeffrey I Cohen

Wei Bu

Yongping Yang

Ivelin Georgiev

Jason Scott McLellan

Lingshu Wang

Kizzmekia S Corbett

Syed M Moin

Gary J Nabel

Baoshan Zhang

Tongqing Zhou

Gwo-Yu Chuang

Guillaume Stewart-Jones

Yaroslav Tsybovsky

Marie Pancera

Man Chen

Gilad Ofek

Mallika Sastry

Jason Gorman

Cinque Soto

Lei Chen

Sanjay Srivatsan

Cheng Cheng

Wing-Pui Kong

Wei Shi

Aliaksandr Druz

Andrew B Ward

Ulrich Baxa

Joseph Van Galen

Nianshuang Wang

Hannah Turner

Kayvon Modjarrad

Robert Kirchdoerfer

Christopher Cottrell

Jesper Pallesen

Neil P King

John Mascola

Chih-Jen Wei

Daniel Ellis

Jorge Fallas

George Ueda

Patrick M McTamney

Jing Yang Wang

Seyhan Boyoglu-Barnum

Rebecca A Gillespie

Jason S Mclellan

Ivelin Stefanov Georgiev

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

Antibodies and compositions of matter useful for the detection, diagnosis and treatment of Epstein Barr Virus (EBV) infection in mammals, and methods of using those compositions of matter for the detection, diagnosis and treatment of EBV infection are described. Also described are proteins, referred to as anti-gp350 antibody probes, and anti-gp350 B-cell probes, that maintain the epitope structure of the CR2-binding region of gp350, but do not bind CR2.

Antibodies and methods for the diagnosis and treatment of Epstein Barr virus infection

Vaccines that elicit broadly protective anti-influenza antibodies. Some vaccines comprise nanoparticles that display HA trimers from influenza virus on their surface. The nanoparticles are fusion proteins comprising a monomeric subunit (e.g., ferritin) joined to the stem region of an influenza HA protein. The fusion proteins self-assemble to form the HA-displaying nanoparticles. The vaccines comprise only the stem region of an influenza HA protein joined to a trimerization domain. Also provided are fusion proteins, and nucleic acid molecules encoding such proteins, and assays using nanoparticles of the invention to detect anti-influenza antibodies.

Stabilized influenza hemagglutinin stem region trimers and uses thereof

Anti-EBV gH antibodies, anti-EBV gL antibodies, anti-EBV gH/gL antibodies, and compositions of matter useful for the detection, diagnosis, prevention, and treatment of Epstein Barr Virus infection in humans, and methods of using those compositions of matter for the same.

Antibodies and methods for the diagnosis, prevention, and treatment of Epstein Barr virus infection

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

Disclosed are Respiratory Syncytial Virus (RSV) antigens including a recombinant RSV F protein stabilized in a prefusion conformation. Also disclosed are nucleic acids encoding the antigens and methods of producing the antigens. Methods for generating an immune response in a subject are also disclosed. In some embodiments, the method is a method for treating or preventing a RSV infection in a subject by administering a therapeutically effective amount of the antigen to the subject.

Prefusion RSV F proteins and their use

Coronavirus S ectodomain trimers stabilized in a prefusion conformation, nucleic acid molecules and vectors encoding these proteins, and methods of their use and production are disclosed. In several embodiments, the coronavirus S ectodomain trimers and/or nucleic acid molecules can be used to generate an immune response to coronavirus in a subject. In additional embodiments, the therapeutically effective amount of the coronavirus S ectodomain trimers and/or nucleic acid molecules can be administered to a subject in a method of treating or preventing coronavirus infection.

Prefusion coronavirus spike proteins and their use

Novel, nanoparticle-based vaccines are provided that elicit an immune response to a broad range of infectious agents, such as influenza viruses. The nanoparticles comprise a heterogeneous population of fusion proteins, each comprising a monomeric subunit of a self-assembly protein, such as ferritin, joined to one or more immunogenic portions of a protein from an infectious agent, such as influenza virus. The fusion proteins self-assemble to form nanoparticles that display a heterogeneous population of immunogenic portions on their surface. When administered to an individual, such nanoparticles elicit an immune response to different strains, types, subtypes and species with in the same taxonomic family. Thus, such nanoparticles can be used to vaccinate an individual against infection by different Types, subtypes and/or strains of infectious agents. Also provided are specific fusion proteins, nucleic acid molecules encoding such fusion proteins and methods of using nanoparticles of the invention to vaccinate individuals.

Multivalent nanoparticle-based vaccines

Disclosed are recombinant insect ferritin nanoparticles that can be used to display two different trimeric antigens at an equal ratio. Also disclosed are nucleic acids encoding the recombinant insect ferritin nanoparticles and methods of producing the recombinant insect ferritin nanoparticles. Methods for eliciting an immune response in a subject are also provided.

Self-assembling insect ferritin nanoparticles

Antibodies and methods for the diagnosis and treatment of Epstein Barr Virus infection

Vaccines that elicit broadly protective anti-influenza antibodies. The vaccines comprise nanoparticles that display HA trimers from Group 2 influenza virus on their surface. The nanoparticles are fusion proteins comprising a monomeric subunit (e.g., ferritin) joined to stabilized stem regions of Group 2 influenza virus HA proteins. The fusion proteins self-assemble to form the HA-displaying nanoparticles. Also provided are fusion proteins, and nucleic acid molecules encoding such proteins, and assays using nanoparticles of the invention to detect anti-influenza antibodies.

Stabilized group 2 influenza hemagglutinin stem region trimers and uses thereof

Antibodies and compositions of matter useful for the detection, diagnosis and treatment of Epstein Barr Virus infection in mammals, and to methods of using those compositions of matter for the same. Also disclosed are proteins, referred to as anti-gp350 antibody probes, and anti-gp350 B-cell probes, that maintain the epitope structure of the CR2-binding region of gp350, but do not bind CR2.

Growing community of inventors

Chevy Chase, MD, United States of America

Masaru Kanekiyo