Immunogenic peptides of influenza virus
Inventors
Golding, Hana • Khurana, Surender
Assignees
US Department of Health and Human Services
Publication Number
US-8778847-B2
Publication Date
2014-07-15
Expiration Date
2028-06-13
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Peptides and polypeptides that elicit immunogenic responses in a mammal; especially neutralizing antibodies, against human and avian influenza strains H1N1, H3N2, H5N1 and H7N7 are disclosed Immunogenic compositions including these peptides, and polypeptides are also provided. Compositions including these peptides and polypeptides with or without adjuvants are disclosed. Nucleic acids and expression cassettes encoding these peptides and polypeptides are also disclosed. Methods of inhibiting infection by influenza, with or without cell entry, are also disclosed using these peptides and polypeptides.
Core Innovation
The invention provides peptides and polypeptides that elicit immunogenic responses, particularly neutralizing antibodies, against human and avian influenza virus strains H1N1, H3N2, H5N1, and H7N7. It includes immunogenic compositions containing these peptides and polypeptides, optionally combined with adjuvants, as well as nucleic acids and expression cassettes encoding them. Methods of inhibiting influenza infection using these peptides and polypeptides, with or without cell entry, are also disclosed.
The invention addresses the challenge of influenza epidemics caused by antigenic shift and drift in viral surface proteins hemagglutinin (HA) and neuraminidase (NA), which lead to variant virus strains. Current vaccines are strain-specific and do not protect against heterotypic influenza viruses, creating a need for new vaccine candidates that provide heterotypic cross-protection and for differential diagnostics to distinguish exposure to avian and seasonal influenza in vaccinated populations.
The invention utilizes whole viral genome phage display libraries expressing complete sets of protein fragments of influenza genes from multiple strains to identify viral epitopes recognized by antibodies from infected or vaccinated subjects. This epitope mapping identifies immunogenic fragments of influenza proteins that elicit protective immune responses, allowing preparation of immunogenic compositions, antagonists, and diagnostic assays. The identified peptides can be used to generate neutralizing antibodies, for passive therapy, and in serological assays for surveillance and differential diagnosis of influenza outbreaks.
Claims Coverage
The claims disclose four independent claims focused on isolated polypeptides and compositions related to an H5N1 HA polypeptide fragment and its uses.
Isolated H5N1 HA polypeptide fragment
An isolated polypeptide corresponding to an H5N1 HA polypeptide fragment consisting of an amino acid sequence with at least 80% identity to amino acids 5 to 247 of SEQ ID NO:129.
Fusion of H5N1 HA polypeptide fragment to a heterologous polypeptide comprising a bacteriophage coat protein
An isolated H5N1 HA polypeptide fragment as above fused to a heterologous polypeptide where the heterologous polypeptide comprises all or a portion of a filamentous bacteriophage coat protein.
Fusion of H5N1 HA polypeptide fragment to a heterologous carrier protein
An isolated H5N1 HA polypeptide fragment as above fused to a heterologous polypeptide selected from bovine serum albumin, keyhole limpet hemacyanin, ovalbumin, mouse serum albumin, and rabbit serum albumin.
Polypeptide bound to solid substrate
The H5N1 HA polypeptide fragment of claim 1 bound to a solid substrate.
Composition comprising H5N1 HA polypeptide fragment and carrier
A composition comprising a carrier and an effective amount of the isolated H5N1 HA polypeptide fragment of claim 1.
Adjuvanted composition for immunization
The composition of claim 5 wherein the carrier is an adjuvant selected from aluminum hydroxide, lipid A, killed bacteria, polysaccharide, mineral oil, Freund's adjuvants, aluminum phosphate, iron, zinc, calcium salt, acylated tyrosine or sugar, CpG oligonucleotide, various polysaccharides, polyphosphazine, biodegradable microsphere, monophosphoryl lipid A, MF59, oil-in-water emulsions AS03 and AS04, ISCOM, and quil A.
The claims cover isolated H5N1 HA polypeptide fragments with defined sequence identity, fusion proteins with bacteriophage or carrier proteins, use on solid substrates, and immunogenic compositions with specific adjuvants, thus protecting the invention's core polypeptides and their therapeutic and diagnostic applications.
Stated Advantages
The peptides provide broad heterotypic neutralizing activity against multiple influenza strains.
They enable differential diagnosis distinguishing human from avian influenza and vaccine-induced from infection-induced antibodies.
The peptides can be used to generate neutralizing antibodies for passive therapy and to analyze immune responses to vaccines.
Documented Applications
Immunization of mammals including humans to generate protective immune responses against influenza virus infections.
Diagnostic assays for serodiagnosis and differential diagnosis of influenza virus subtypes and strains, including identifying H5N1 infections and distinguishing infection from vaccination.
Use as reagents in surveillance assays to monitor influenza outbreaks and vaccine efficacy.
Production of monoclonal or humanized antibodies for therapeutic use against influenza viruses.
Interested in licensing this patent?