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Abstract
Methods for providing novel compositions useful as influenza immunogens are provided. The compositions enable a host response to immunogen sites normally not recognized by a host. The novel immunogens can be used as vaccines or to develop antibodies.
Core Innovation
The invention relates to an influenza immunogen/vaccine strategy using immune refocusing, also referred to as immunodampening, of immunodominant HA and/or NA epitopes. The approach redirects immune responses toward non-dominant or conserved epitopes rather than focusing on immunodominant influenza epitopes, and is described as mitigating issues of subtype/strain specificity and supporting broader cross-strain protection.
The disclosed strategy includes epitope definitions and immune refocusing terminology, including immunodominant epitope, immunodampening, immune refocusing, and immune refocusing treatment. Antigen formats include recombinant HA/NA subunits, virus-like particles, and recombinant influenza viruses, with epitope content central to the immune refocusing concept.
Engineered HA muteins are described with modifications intended to alter immune recognition, including N-linked glycosylation sequon insertions, deletions, and charge-altering substitutions. Examples describe enhanced heterologous hemagglutination inhibition and virus neutralization titers in mouse studies.
Claims Coverage
The relevant independent claim provides a polypeptide or virus comprising a human influenza epitope defined by specified SEQ ID NO amino acid sequence selections. The inventive coverage centers on epitope-defined polypeptides or viruses, with dependent embodiments specifying recombinant virus, fusion protein, and VLP formats.
Epitope-defined human influenza polypeptide or virus sequence selection
A polypeptide or virus comprising an epitope of a human influenza virus, wherein the epitope comprises an amino acid sequence selected from SEQ ID NO:45-48, 50-52, 54-59, 61-66, 71, 74-76 or 77.
Human, avian, swine, canine, or horse influenza virus specificity
The polypeptide or virus of claim 1, wherein the influenza virus is a human, avian, swine, canine, or horse influenza virus.
Recombinant virus comprising the epitope polypeptide
A recombinant virus comprising the polypeptide of claim 1.
Fusion protein comprising the epitope polypeptide
A fusion protein comprising the polypeptide of claim 1.
VLP comprising a therapeutic molecule
A VLP comprising a therapeutic molecule.
The claim set centers on influenza epitope-containing polypeptides or viruses defined by specified SEQ ID NO amino acid sequence selections, and extends to recombinant virus, fusion protein, and VLP embodiments, with additional host specificity in related dependents.
Stated Advantages
Broader cross-strain protection by redirecting immune responses toward non-dominant or conserved epitopes rather than immunodominant HA/NA epitopes.
Mitigation of issues of subtype/strain specificity.
Enhanced heterologous hemagglutination inhibition and virus neutralization titers in mouse studies.
Documented Applications
Influenza immunogen/vaccine use incorporating immune refocusing to redirect immune responses toward non-dominant or conserved epitopes.
Immunogen/antigen formats including recombinant HA/NA subunits, VLPs, and recombinant influenza viruses containing the specified epitopes.
Preclinical evaluation in mouse studies using heterologous hemagglutination inhibition and virus neutralization assays.
Safety/tolerability testing in relevant animal models.
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