The Scripps Research Institute

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

Linling He

Jiang Zhu

Ian A Wilson

Leopold Kong

Dennis R Burton

Andrew B Ward

Natalia De Val

Anshul Chaudhary

Yiming Shao

Li Ren

Jiandong Liu

Yi-Zong Lee

Netanel Tzarum

Yuxing Li

Mansun Law

Bin Ju

Erick Giang

Yajing Chen

The present invention provides novel nanoparticle presented vaccine compositions that are stabilized with a locking domain. Various immunogens can be employed in the preparation of the vaccine compositions, including viral immunogens such as HIV-1 and Ebola viral immunogens, and non-viral immunogens such as immunogens derived from bacteria, parasites and mammalian species. The invention also provides methods of using such vaccine compositions in various therapeutic applications, e.g., for preventing or treating viral infections.

Nanoparticle vaccines with novel structural components

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 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 scaffolded HIV-1 vaccine immunogens. Some of the scaffolded immunogens contain a soluble gp140 trimer linked to the N-terminus of the nanoparticle subunit and a T-helper epitope that is fused via a short peptide spacer to the C-terminus of the nanoparticle subunit. Some other immunogens of the invention contain a soluble gp140 trimer protein that is linked to a stable nanoparticle via a short peptide spacer that is a T-helper epitope. Some of the scaffolded immunogens contain a gp140 trimer immunogen presented on a nanoparticle platform formed with I3-01 protein, E2p, or variants of protein 1VLW. Also provided in the invention are nucleic acids that encode the various vaccine immunogens described herein, and expression vectors and host cells harboring the nucleic acids. The invention further provides methods of using the scaffolded HIV-1 vaccine immunogens for preventing or treating HIV infections.

Scaffolded HIV-1 Env GP140 trimer immunogen

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.

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San Diego, CA, United States of America

Linling He