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

Dana-farber-cancer Institute Inc.

Columbia University

University of Washington

Leland Stanford Junior University

University of Pennsylvania

Duke University

The Scripps Research Institute

Boston University

International Aids Vaccine Initiative

Other

Los Alamos National Security, LLC

Triad National Security, LLC

The University of Alabama

Sanofi

Peter D Kwong

John R Mascola

Tongqing Zhou

Baoshan Zhang

Yongping Yang

Gary J Nabel

Ivelin Georgiev

Barney S Graham

Michael Gordon Joyce

Gwo-Yu Chuang

Guillaume Stewart-Jones

Mark Connors

Richard Wyatt

Xueling Wu

Zhi-yong Yang

Joseph G Sodroski

Aliaksandr Druz

Jeffrey C Boyington

Masaru Kanekiyo

Jason Scott McLellan

Wing-Pui Kong

Young Do Kwon

Antonio Lanzavecchia

Peter L Collins

Davide Corti

Ursula J Buchholz

Cheng Cheng

William Ray Schief

Beatrice H Hahn

John Mascola

Wei Shi

Hadi M Yassine

Ling Xu

Barton F Haynes

Dennis R Burton

Bette T Korber

Amos B Smith, Iii

Huawei Qiu

Hua-Xin Liao

Wayne C Koff

Sanjay K Phogat

Ercole Rao

Christian Lange

George M Shaw

Pascal Raymond Georges Poignard

Richard Schwartz

David Michael Jones

Jochen Kruip

Ernesto Freire

Christian Beil

Marie Pancera

Gilad Ofek

Man Chen

Yaroslav Tsybovsky

Li Ou

Jiang Zhu

Rebecca S Rudicell

Cinque Soto

Ulrich Baxa

Mario Roederer

Yuxing Li

Jinghe Huang

Paul Thomas

Carl-Magnus Hogerkorp

Barna Dey

Leo Laub

Shi-Hua Xiang

Rebecca M Lynch

Wen Yuan

Emily Rundlet

Thomas B Kepler

Natalie Mackow

Rita Chen

Joel R Courter

Zhi-Yong Yang

Jochen Beninga

Mallika Sastry

Jason Gorman

Wayne A Hendrickson

Joseph Van Galen

Kai Xu

Michael Farzan

Feng Gao

Shirin Munir

Wulf Dirk Leuschner

Bo Liang

Lei Chen

Scott D Boyd

Sanjay Srivatsan

Anne Schaap Nutt

Priyamvada Acharya

Syed M Moin

Lawrence Shapiro

Alexander W Sun

Amy M Princiotto

Judith M LaLonde

Navid Madani

Jonathan Cooper

Kevin Carlton

Michael Bender

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

Embodiments of a recombinant human Parainfluenza Virus (hPIV) F ectodomain trimer stabilized in a prefusion conformation are provided. Also disclosed are nucleic acids encoding the hPIV F ectodomain trimer and methods of producing the hPIV 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 inhibiting a hPIV infection in a subject by administering a effective amount of the recombinant hPIV F ectodomain trimer to the subject.

Prefusion PIV F immunogens and their use

Metapneumovirus (MPV) F proteins 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 MPV F proteins and/or nucleic acid molecules can be used to generate an immune response to MPV in a subject. In additional embodiments, the therapeutically effective amount of the MPV F ectodomain trimers and/or nucleic acid molecules can be administered to a subject in a method of treating or preventing MPV infection.

Recombinant metapneumovirus F proteins and their use

Antibodies and antigen binding fragments that specifically bind to HIV-1 Env and neutralize HIV-1 are disclosed. Nucleic acids encoding these antibodies, vectors and host cells are also provided. Methods for detecting HIV-1 using these antibodies are disclosed. In addition, the use of these antibodies, antigen binding fragment, nucleic acids and vectors to prevent and/or treat an HIV-1 infection is disclosed.

Neutralizing antibodies to HIV-1 Env and their use

Embodiments of immunogens based on the HIV-1 Env fusion peptide and methods of their use and production are disclosed. Nucleic acid molecules encoding the immunogens are also provided. In several embodiments, the immunogens can be used to generate an immune response to HIV-1 Env in a subject, for example, to treat or prevent an HIV-1 infection in the subject.

HIV-1 Env fusion peptide immunogens and their use

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

HIV-1 Env ectodomain trimers stabilized in a prefusion mature closed conformation and methods of their use and production are disclosed. In several embodiments, the HIV-1 Env ectodomain trimers and/or nucleic acid molecules can be used to generate an immune response to HIV-1 in a subject. In additional embodiments, the therapeutically effective amount of the HIV-1 Env ectodomain trimers can be administered to a subject in a method of treating or preventing HIV-1 infection.

Recombinant HIV-1 envelope proteins and their use

Neutralizing antibodies that specifically bind to HIV-1 Env and antigen binding fragments of these antibodies are disclosed. Nucleic acids encoding these antibodies, vectors and host cells are also provided. Methods for detecting HIV-1 using these antibodies are disclosed. In addition, the use of these antibodies, antigen binding fragment, nucleic acids and vectors to prevent and/or treat an HIV-1 infection is disclosed.

Neutralizing antibodies to HIV-1 GP41 and their use

Substitutions-modified prefusion RSV F proteins and their use

Immunogens comprising a recombinant HIV-1 Env ectodomain trimer stabilized in a prefusion closed conformation and methods of their use and production are disclosed. In several embodiments, the immunogen can be used to elicit an immune response to HIV-1 in a subject.

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.

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New York, NY, United States of America

Peter D Kwong