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

Dartmouth College

Vanderbilt University

US Government As Represented by the Secretary of the Army

The Scripps Research Institute

Universiteit Gent

Institute for Research in Biomedicine

Humabs Biomed Sa

University of Washington

Glaxosmithkline Biologicals Sa

Vib Vzw

Xiamen University

Xiamen Innovax Biotech Co., Ltd.

Korea Center for Disease Control and Prevention

Yang Sheng Tang Company Limited

Barney S Graham

Masaru Kanekiyo

Michael Gordon Joyce

Jason Scott McLellan

Peter D Kwong

John R Mascola

Jeffrey C Boyington

Hadi M Yassine

Yongping Yang

Man Chen

Lingshu Wang

Baoshan Zhang

Ivelin Georgiev

John Mascola

Guillaume Stewart-Jones

Wing-Pui Kong

Kizzmekia S Corbett

Wei Shi

Marie Pancera

Mallika Sastry

Julie Ledgerwood

Cinque Soto

Tongqing Zhou

Aliaksandr Druz

Yaroslav Tsybovsky

Ulrich Baxa

Joseph Van Galen

Syed M Moin

Peter L Collins

Ursula J Buchholz

Julian Davies

Gwo-Yu Chuang

Bryan Edward Jones

Christopher Carl Frye

Gilad Ofek

Li Ou

Qing Chai

Shirin Munir

Jason Gorman

Paul Thomas

Bo Liang

Jeffrey Streetman Boyles

Lei Chen

Ester Falconer

Ganapathy Gopalrathnam

Kathryn Westendorf

Jörg Hendle

Anne Schaap Nutt

John Michael Sauder

Natalie Mackow

Anna Pustilnik

Stefanie Zentelis

Olubukola Abiona

Krithika Muthuraman

Emily Rundlet

Wing-pui Kong

Yi Zhang

Denisa Foster

Kevin Jepson

Sanjay Srivatsan

Antonio Lanzavecchia

Davide Corti

Cheng Cheng

Nancy J Sullivan

Xavier Saelens

Andrew B Ward

Bert Schepens

Nianshuang Wang

Hannah Turner

Kayvon Modjarrad

Robert Kirchdoerfer

Christopher Cottrell

Jesper Pallesen

Theodore C Pierson

Kimberly A Dowd

Iebe Rossey

Morgan Gilman

Sabue Mulangu

Jean-Jacques Muyembe-Tamfun

John Trefry

Daphne Stanley

Ningshao Xia

Neil P King

Daniel Ellis

Min Zhao

Jorge Fallas

George Ueda

Yi-Wei Tang

Dong Yu

Mayuri Sharma

Sung-youl Ko

Eun Sung Yang

Christina R Demaso

Rebecca S Pelc

Adrian Creanga

Leda R Castilho

Zizheng Zheng

Liangmin Huang

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

Embodiments of a recombinant Respiratory Syncytial Virus (RSV) F ectodomain trimer stabilized in a prefusion conformation are provided. Also disclosed are nucleic acids encoding the RSV F ectodomain trimer and methods of producing the RSV F ectodomain trimer. Methods for inducing an immune response in a subject are also disclosed. In some embodiments, the method can be a method for treating or preventing a RSV infection in a subject by administering a therapeutically effective amount of the recombinant RSV F ectodomain trimer to the subject.

Prefusion RSV F proteins and their use

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

Antibodies that bind SARS-CoV spike protein, SARS-CoV-2 spike protein, and methods of using same for treating or preventing conditions associated with SARS or COVID-19 and for detecting SARS-CoV or SARS-CoV-2.

Anti-coronavirus antibodies and methods of use

The present invention relates to monoclonal antibodies for a spike protein of the Middle East respiratory syndrome coronavirus (MERS-CoV), and a use thereof. Particularly, monoclonal antibodies 77-A5, 77-A6, 90-A3, 90-A9, 90-B2, 90-B7, 90-C4, 90-E5, 90-E6, 90-F1 and 90-F2 according to the present invention have excellent attachment force with respect to a full-length spike protein of MERS-CoV and the S1 domain of the protein, and, of the monoclonal antibodies, the monoclonal antibodies 90-F1, 90-E5, 90-E6, 90-F2, 77-A5 and 77-A6 have excellent attachment force with respect to an RBD antigen of MERS-CoV. Also, the antibodies 77-A5, 77-A6, 90-E5, 90-E6, 90-F1 and 90-F2 exhibit neutralizing capacity with respect to a MERS pseudovirus and MERS-CoV, and the antibodies 90-B2 and 90-B7 exhibit neutralizing capacity only with respect to MERS-CoV. Further, the monoclonal antibodies have a particular monomeric form, and have excellent stability and thus may be useful for treating or diagnosing MERS.

Monoclonal antibody for spike protein of middle east respiratory syndrome coronavirus, and use thereof

Recombinant paramyxoviruses including a viral genome encoding a heterologous gene are provided. In several embodiments, the recombinant paramyxovirus is a recombinant parainfluenza virus, such as a recombinant PIV3 including a viral genome encoding a heterologous respiratory syncytial virus F ectodomain linked to the transmembrane domain and the cytoplasmic tail of the F protein from the PIV3. Nucleic acid molecules including the genome of a recombinant paramyxoviruses are also provided. The recombinant viruses may advantageously be used in vaccine formulations, such as for vaccines against parainfluenza virus and respiratory syncytial virus.

Recombinant human parainfluenza virus type 1 expressing a chimeric RSV/HPIV1 f protein and uses thereof

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.

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

Embodiments of immunogens comprising a recombinant Nipah virus (NiV) F ectodomain trimer stabilized in a prefusion conformation are provided. Also provided are embodiments of immunogens comprising chimeric proteins comprising the recombinant NiV F ectodomain trimer and one or more G ectodomains, a multimer of NiV G ectodomains, and protein nanoparticles comprising the recombinant NiV F ectodomain trimer or an NiV G ectodomain. Also disclosed are nucleic acids encoding the immunogens and methods of their production. Methods for inducing an immune response in a subject by administering a disclosed immunogen to the subject are also provided. In some embodiments, the immune response treats or inhibits NiV infection in a subject.

Nipah virus immunogens and their use

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

Compounds useful as components of immunogenic compositions for the induction of an immunogenic response in a subject against viral infection, methods for their use in treatment, and processes for their manufacture are provided herein. The compounds comprise a nucleic acid construct comprising a sequence which encodes a Zika virus antigen.

Zika viral antigen constructs

Growing community of inventors

Rockville, MD, United States of America

Barney S Graham