Influenza hemagglutinin antibodies, compositions and related methods
Inventors
Yusibov, Vidadi • Mett, Vadim • Chichester, Jessica • Goldschmidt, Lauren
Assignees
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Publication Number
US-8784819-B2
Publication Date
2014-07-22
Expiration Date
Abstract
Antibodies against influenza hemagglutinin, compositions containing the antibodies, and methods of using the antibodies are provided herein.
Core Innovation
The invention relates to plant-based production platforms for influenza hemagglutinin (HA) antigens and HA-binding monoclonal antibodies, including plant viral vectors that include movement protein (MP) and coat protein (CP) functions. The platform supports viral replication and spread by infecting multiple plant cells, followed by harvesting leaves to obtain HA-related products or further plant-derived materials. MP/CP configurations include cases that lack MP and/or CP while still supporting the described plant-based production workflow.
The invention further includes generation of clonal root lines via Agrobacterium rhizogenes-induced hairy roots carrying viral vectors, with emphasis on high inheritance rates of the viral vectors in selected clonal root lines. The described approach supports stability of HA expression in selected root lines and is presented as enabling scale-up without certain culture hormones. It also covers clonal root cell lines and clonal plant cell lines derived from viral-vector-containing clonal lineages, including a high percentage of vector-containing cells.
In addition, the invention covers generation of clonal whole plants from clonal lineages derived from the viral-vector system. The document also describes sprouted seedling expression systems in contained regulatable environments, including inducible promoters and viral or transgenic cassettes, as well as transformation approaches including Agrobacterium-mediated methods, direct integration, and viral transformation. The production and isolation scope includes HA polypeptides and plant-produced antibodies for therapeutic, prophylactic, and diagnostic use, with expression and delivery concepts including agrobacterial launch vector for agroinfiltration and transient systemic expression.
The invention also relates to isolated monoclonal antibodies that bind hemagglutinin and inhibit hemagglutination. The antibody is selected from sequence-defined embodiments characterized by a light chain variable region amino acid sequence and a heavy chain variable region amino acid sequence, including SEQ ID NO:79 with SEQ ID NO:78, and SEQ ID NO:81 with SEQ ID NO:80. It further provides an antibody-binding fragment that binds hemagglutinin and inhibits hemagglutination, wherein the fragment comprises the specified light chain variable region and heavy chain variable region amino acid sequences and is limited to scFv, Fv, Fab', Fab, diabody, linear antibody, or F(ab')2.
Claims Coverage
The partial content provided includes six independent claims. Across these claims, the inventive features are defined by plant-based viral-vector production platforms for influenza HA-related products and by sequence-defined hemagglutinin-binding antibodies and antigen-binding fragments that inhibit hemagglutination.
Plant-based viral-vector production platform for influenza hemagglutinin-related products
A plant-based production platform for influenza hemagglutinin (HA) antigens and HA-binding monoclonal antibodies, including plant viral vectors that include movement protein (MP) and coat protein (CP) functions, support viral replication and spread by infecting multiple plant cells, and include cases that lack MP and/or CP while still supporting the described workflow.
Clonal root lines carrying viral vectors with high inheritance rates
Generation of clonal root lines via Agrobacterium rhizogenes-induced hairy roots carrying viral vectors, with high inheritance rates of the viral vectors in selected clonal root lines, stability of HA expression, and scale-up without certain culture hormones.
Clonal root cell lines and clonal plant cell lines derived from viral-vector-containing lineages
Clonal root cell lines and clonal plant cell lines derived from viral-vector-containing clonal lineages, including a high percentage of vector-containing cells.
Clonal whole plants from viral-vector-derived clonal lineages
Generation of clonal whole plants from clonal lineages derived from the viral-vector system.
Hemagglutinin-binding monoclonal antibody with sequence-defined variable regions
An isolated monoclonal antibody that binds hemagglutinin and inhibits hemagglutination, comprising either the light chain variable region amino acid sequence set forth in amino acids 1-97 of SEQ ID NO:79 and the heavy chain variable region amino acid sequence set forth in amino acids 1-115 of SEQ ID NO:78, or the light chain variable region amino acid sequence set forth in amino acids 1-96 of SEQ ID NO:81 and the heavy chain variable region amino acid sequence set forth in amino acids 1-112 of SEQ ID NO:80.
Hemagglutinin-binding antigen-binding fragment in defined fragment formats
An antigen-binding fragment of an antibody that binds hemagglutinin and inhibits hemagglutination, comprising the specified variable regions and limited to scFv, Fv, Fab', Fab, diabody, linear antibody, or F(ab')2.
The coverage is centered on plant-based HA production and on hemagglutinin binding with inhibition of hemagglutination, defined by sequence-specific light and heavy variable regions and, for fragments, by the listed antigen-binding fragment formats.
Stated Advantages
Allows stability of HA expression in selected clonal root lines.
Enables scale-up without certain culture hormones.
Inhibit hemagglutination.
Enable H5 typing via detectable binding.
Provide protective efficacy in animal challenge models.
Documented Applications
Production of HA polypeptides and plant-produced antibodies for therapeutic use.
Production of HA polypeptides and plant-produced antibodies for prophylactic use.
Production of HA polypeptides and plant-produced antibodies for diagnostic use.
Therapeutic use, including protective efficacy in animal challenge models.
Diagnostic use for H5 typing via detectable binding.
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