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

Dartmouth College

The University of Texas System

The Scripps Research Institute

Universiteit Gent

Vib Vzw

Xiamen University

Xiamen Innovax Biotech Co., Ltd.

Calder Biosciences Inc.

V18 Vzw

Jason Scott McLellan

Barney S Graham

Michael Gordon Joyce

Peter D Kwong

Man Chen

Baoshan Zhang

Tongqing Zhou

Masaru Kanekiyo

Yongping Yang

Guillaume Stewart-Jones

Nianshuang Wang

Peter L Collins

Ursula J Buchholz

Ivelin Georgiev

Jeffrey C Boyington

Gwo-Yu Chuang

Marie Pancera

Gilad Ofek

Mallika Sastry

Shirin Munir

Jason Gorman

Cinque Soto

Bo Liang

Lei Chen

Sanjay Srivatsan

Anne Schaap Nutt

Natalie Mackow

Roberto Mariani

Hadi M Yassine

Xavier Saelens

Andrew B Ward

Kizzmekia S Corbett

Bert Schepens

Peter Joseph Alff

Claudio Bertuccioli

Hannah Turner

Scott Rush

Ching-Lin Hsieh

Christopher Cottrell

Jesper Pallesen

Robert Kirchdoerfer

Iebe Rossey

Morgan Gilman

Ningshao Xia

John Mascola

Christopher Marshall

Christopher P Marshall

Min Zhao

Rebecca Loomis

Liangmin Huang

Zizheng Zheng

Christopher Patrick Marshall

Provided herein are engineered hMPV F proteins. In some aspects, the engineered F proteins exhibit enhanced conformational stability and/or antigenicity. Methods are also provided for use of the engineered F proteins as diagnostics, in screening platforms, and/or in vaccine compositions.

Prefusion-stabilized hMPV F proteins

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

In some embodiments, the present invention provides respiratory syncytial virus (RSV) F proteins, polypeptides and protein complexes that comprise one or more cross-links to stabilize the protein, polypeptide or protein complex in its pre-fusion conformation. In some embodiments the present invention provides RSV F proteins, polypeptides and protein complexes comprising one or more mutations to facilitate such cross-linking. In some embodiments the present invention provides compositions comprising such proteins, polypeptides or protein complexes, including vaccine compositions, and methods of making and using the same.

Conformationally stabilized RSV pre-fusion F proteins

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

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

Recombinant human/bovine parainfluenza virus 1 (HPIV1) expressing a chimeric RSV/HPIV1 F protein and uses thereof

The present invention relates to immunoglobulin single variable domains (ISVDs) that are directed against respiratory syncytial virus (RSV). More specifically, it relates to ISVDs that bind to the prefusion form of the fusion (F) protein of RSV. The invention relates further to the use of these ISVDs for prevention and/or treatment of RSV infections, and to pharmaceutical compositions comprising these ISVDs.

Immunoglobulin single variable domain antibody against RSV prefusion F protein

Disclosed are immunogens including a recombinant RSV F protein stabilized in a prefusion conformation. Also disclosed are nucleic acids encoding the immunogens and methods of producing the immunogens. 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 immunogen to the subject.

Recombinant human/bovine parainfluenza virus 3 (B/HPIV3) expressing a chimeric RSV/BPIV3 F protein and uses thereof

Growing community of inventors

Austin, TX, United States of America

Jason Scott McLellan