The Scripps Research Institute

International Aids Vaccine Initiative

Cornell University

The Texas A&m University System

National Center for Aids/std Control and Prevention, Chinese Center for Disease Control and Prevention

Ian A Wilson

Linling He

Jiang Zhu

Dennis R Burton

Andrew B Ward

Leopold Kong

Richard A Lerner

Natalia De Val

Dana L Johnson

Linda K Jolliffe

Hongkai Zhang

Anshul Chaudhary

Enrico A Stura

Oded Livnah

John S Moore

C Richter King

Vaughn V Smider

Andre Marozsan

Simon Hoffenberg

Michael P Caulfield

Devin Sok

Waithaka Mwangi

Rogier W Sanders

Li Ren

Yiming Shao

Albert Cupo

Jiandong Liu

Yajing Chen

Yi-Zong Lee

Michael Criscitiello

Erick Giang

Mansun Law

Xueyong Zhu

Rajesh Grover

Jean-Philippe Julien

P J Klasse

Hansi Dean

Robert Pejchal

Robyn L Stanfield

Netanel Tzarum

Yuxing Li

Bin Ju

Per Johan Klasse

Michael Caulfield

Rogier Sanders

Jean-Phillippe Julien

John Moore

The present invention provides redesigned soluble coronavirus S protein derived immunogens that are stabilized via specific modifications in the wildtype soluble S sequences. Also provided in the invention are nanoparticle vaccines that contain the redesigned soluble S immunogens displayed on self-assembling nanoparticles. Polynucleotide sequences encoding the redesigned immunogens and the nanoparticle vaccines are also provided in the invention. The invention further provides methods of using the vaccine compositions in various therapeutic applications, e.g., for preventing or treating coronaviral infections.

Stabilized coronavirus spike (s) protein immunogens and related vaccines

The present invention provides novel engineered influenza hemagglutinin (HA) proteins, related polynucleotide sequences, and vaccine compositions including nanoparticle compositions. Relative to a wildtype HA protein, the engineered HA proteins are stabilized via substitutions of one or more conserved residues in the HA2 ectodomain with hydrophobic residues. The invention also provides methods of using such vaccine compositions in various therapeutic applications, e.g., for preventing or treating influenza viral infections.

Stabilized hemagglutinin (HA) trimers as influenza vaccine antigens

The present invention provides novel engineered Ebolavirus GP proteins and polypeptides, scaffolded vaccine compositions that display the engineered proteins, and polynucleotides encoding the engineered proteins and scaffolded vaccine compositions. The invention also provides methods of using such engineered Ebolavirus GP proteins and vaccine compositions in various therapeutic applications, e.g., for preventing or treating Ebolavirus infections.

Compositions and methods related to ebolavirus vaccines

Stabilized coronavirus spike (S) protein immunogens and related vaccines

The present disclosure relates to methods for generating broadly neutralizing bovine anti-HIV Env antibodies, compositions comprising the broadly neutralizing bovine antibodies, and methods of treatment or prevention of HIV using the broadly neutralizing bovine antibodies. In certain embodiments, a broadly neutralizing bovine antibody comprises a polyclonal F(ab) or F(ab')2 fragment. In certain embodiments, a broadly neutralizing bovine antibody comprises a humanized bovine monoclonal antibody.

Rapid elicitation of broadly neutralizing antibodies to HIV Env

The present invention provides HIV-1 vaccine immunogens. Some of the immunogens contain a soluble gp140-derived protein that harbors a modified N-terminus of the HR1 region in gp41. Some of the immunogens contain an HIV-1 Env-derived trimer protein that is presented on a nanoparticle platform. The invention also provides methods of using the HIV-1 vaccine immunogens for eliciting an immune response or treating HIV infections.

HIV-1 GP140 immunogens comprising modified NHR1 regions that stabilize pre-fusion envelope conformations

The present invention provides novel engineered Ebolavirus GP proteins and polypeptides, as well as scaffolded vaccine compositions that display the engineered proteins. The invention also provides methods of using such engineered Ebolavirus GP proteins and vaccine compositions in various therapeutic applications, e.g., for preventing or treating Ebolavirus infections.

Nucleic acids encoding HIV-1 GP140 immunogens comprising modified NHR1 regions that stabilize pre-fusion conformations

The present invention provides novel engineered HCV E2 polypeptide immunogens and related vaccine compositions that display the engineered E2 polypeptides. The invention also provides methods of using such immunogens and vaccine compositions in various therapeutic applications, e.g., for preventing or treating HCV infections.

Engineered HCV E2 immunogens and related vaccine compositions

Broadly neutralizing antibodies against HIV-1 which specifically bind to gp120 of HIV-1, a method of preparing such antibodies and the use thereof are provided.

Broadly neutralizing antibodies against HIV-1 and use thereof

HIV-1 GP140 immunogens comprising modified NHR1 regions that stabilize pre-fusion conformations

The invention provides methods for identifying protein modulators (e.g., antibody agonists) of eukaryotic cells. The methods typically involve expressing a combinatorial agent library (e.g., via lentiviral vectors) inside a eukaryotic cell type (e.g., a mammalian cell) and then directly selecting for agents (e.g., antibodies) that are agonist of a target molecule (e.g., a signaling receptor) that modulates a phenotype of or elicits a cellular response in the cell. Some related methods involve co-culturing a cell expressing a combinatorial agent library and a second cell, and then selecting agents that modulate a phenotype of or elicit a cellular response in the second cell. Preferably, the agents are antibodies and are introduced into and expressed in the starting cells under conditions each individual cell expresses no more than 3 different members of the antibody library. In addition, the invention provides methods for identifying protein agonists that capable of reprograming or trans-differentiating a target cell. Also provided in the invention are specific agonist antibodies of signaling receptors or biomolecules that modulate a phenotype or effectuate a cellular response in a eukaryotic cell (e.g., agonist antibodies of EpoR, TpoR or G-CSFR). Further provided in the invention are methods for selecting from combinatorial antibody libraries bispecific antibodies that can regulate cell phenotypes.

Methods and compositions related to modulators of eukaryotic cells

The invention relates to an immunogenic HIV-1 gp120 mini V3 loop, which is a truncated version of the full-length gp120 V3 loop useful for crystallization with antibodies that recognize carbohydrate moieties. The invention also relates to the structure of a broadly neutralizing antibody as a complex with a glycosylated gp120 outer domain, as determined by crystallographic techniques, and the confirmation that a glycosylated gp120 outer domain has a functional relevant conformation, as well as the determination of key residues on a glycosylated gp120 outer domain, and uses thereof and compounds and compositions therefrom. Furthermore, the invention also relates to other peptides and mimetic peptides, which bind to broadly neutralizing antibodies.

HIV-1 gp120 mini V3 loop and uses thereof

The present application relates to novel HIV-1 envelope glycoproteins, which may be utilized as HIV-1 vaccine immunogens, and antigens for crystallization, electron microscopy and other biophysical, biochemical and immunological studies for the identification of broad neutralizing antibodies. The present invention encompasses the preparation and purification of immunogenic compositions, which are formulated into the vaccines of the present invention.

HIV-1 envelope glycoprotein

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La Jolla, CA, United States of America

Ian A Wilson