Calder Biosciences Inc.

Avatar Medical

Other

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

University of Pittsburgh

Vaxine Pty Ltd

Avatar Biotechnologies, Inc.

Christopher P Marshall

Peter Joseph Alff

Claudio Bertuccioli

Joseph P Errico

Roberto Mariani

Mark Andrew Yondola

Alexander Hoffman

Paul B Marshall

Jason Scott McLellan

Nikolai Petrovsky

Mark Yondola

Aaron Zomback

Sonal Gidwani

Kerry McGarr Empey

Disclosed herein are compositions for vaccination against respiratory syncytial virus (RSV) comprising a RSV F polypeptide stabilized in a prefusion conformation and an inulin adjuvant. Also disclosed herein are methods of vaccinating a subject against a respiratory syncytial virus (RSV) infection comprising administering to the subject an RSV F polypeptide stabilized in a prefusion conformation and an inulin adjuvant. In some embodiments, the subject is a female, and the method can reduce RSV infection in the subject and/or in the offspring of the subject. In some embodiments, the method decreases vaccine-enhanced respiratory disease (VERD) and/or eosinophilia in the subject or offspring of the subject.

Compositions and methods for vaccination against respiratory syncytial virus infection

The present invention provides mutant RSV F molecules, such as those that can be, or are stabilized, in a pre-fusion conformation by the introduction of one or more DT cross-links. The present invention also provides methods of making such mutant RSV F molecules, compositions comprising such mutant RSV F molecules, and methods of use of such mutant RSV F molecules, for example in vaccination methods, therapeutic methods, and antibody production methods.

Conformationally stabilized RSV pre-fusion F proteins

In some embodiments the present invention provides influenza hemagglutinin ('HA') polypeptides, proteins, and protein complexes that comprise a stalk domain that is engineered to facilitate maintenance of its native trimeric conformation, even if the head domain of the HA protein is removed or disrupted. In some embodiments, the present invention provides compositions comprising such polypeptides, proteins, and protein complexes, and methods of use of such proteins and compositions, for example as vaccine immunogens.

Influenza hemagglutinin proteins and methods of use thereof

The present invention provides methods of making engineered viral proteins and protein complexes that are useful as vaccine immunogens, engineered viral proteins and protein complexes made using such methods, and pharmaceutical compositions comprising such engineered viral proteins and protein complexes. Such engineered viral proteins and protein complexes may comprise one or more cross-links that stabilize the conformation of an antibody epitope, such as a quaternary neutralizing antibody, and may exhibit an enhanced ability to elicit a protective immune response when administered to a subject as a component of a vaccine.

Conformationally specific viral immunogens

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.

Isolated polypeptides or polypeptide chains are modified by di-tyrosine cross-linking such that they retain at least one functional activity. In one embodiment, the isolated polypeptide or polypeptide chains comprise at least one di-tyrosine cross-link, wherein at least one tyrosine of the di-tyrosine cross-link originates from a point mutation to tyrosine, and wherein the di-tyrosine cross-linked protein retains at least one function displayed by the protein in the absence of di-tyrosine cross-linking. In another embodiment, the di-tyrosine cross-linked polypeptide or polypeptide chain has enhanced stability compared to the same polypeptide or polypeptide chain in the absence of di-tyrosine cross-linking. A method for stabilization of a polypeptide or polypeptide complex, by the introduction of intra-polypeptide and/or inter-polypeptide di-tyrosine bonds, which simultaneously maintains the structure and function of the polypeptide or polypeptide complex is also described.

Stabilized proteins

Isolated polypeptides or polypeptide chains are modified by di-tyrosine cross-linking such that the retain at least one functional activity. In one embodiment, the isolated polypeptide or polypeptide chains comprise at least one di-tyrosine cross-link, wherein at least one tyrosine of the di-tyrosine cross-link originates from a point mutation to tyrosine, and wherein the di-tyrosine cross-linked protein retains at least one function displayed by the protein in the absence of di-tyrosine cross-linking. In another embodiment, the di-tyrosine cross-linked polypeptide or polypeptide chain has enhanced stability compared to the same polypeptide or polypeptide chain in the absence of di-tyrosine cross-linking. A method for stabilization of a polypeptide or polypeptide complex, by the introduction of intra-polypeptide and/or inter-polypeptide di-tyrosine bonds, which simultaneously maintains the structure and function of the polypeptide or polypeptide complex is also described.

Growing community of inventors

Brooklyn, NY, United States of America

Christopher P Marshall