Materials and methods for respiratory disease control in canines
Inventors
CRAWFORD, PATTI CYNTHIA • Gibbs, Paul J. • Dubovi, Edward J. • Donis, Ruben Omar • Katz, Jacqueline • Klimov, Alexander I. • Lakshmanan, Nallakannu P. • Lum, Melissa Anne • Goovaerts, Daniel Ghislena Emiel • Mellencamp, Mark William • Cox, Nancy J. • Castleman, William L.
Assignees
Cornell Research Foundation Inc • University of Florida Research Foundation Inc • US Department of Health and Human Services
Publication Number
US-10258686-B2
Publication Date
2019-04-16
Expiration Date
2026-04-21
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Abstract
The subject invention pertains to isolated influenza virus that is capable of infecting canids and causing respiratory disease in the canid. The subject invention also pertains to compositions and methods for inducing an immune response against an influenza virus of the present invention. The subject invention also pertains to compositions and methods for identifying a virus of the invention and diagnosing infection of an animal with a virus of the invention.
Core Innovation
The invention discloses an isolated influenza virus capable of infecting canids and causing respiratory disease. It also provides compositions and methods, including vaccines, for inducing an immune response against such influenza viruses, particularly those comprising specific hemagglutinin (HA) antigens of subtypes H3 and H7, derived from equine influenza virus antigen homologs. The polynucleotide and polypeptide sequences of the virus, including various functional fragments and variants, are detailed, alongside methods for virus detection and diagnosis.
The background addresses the problem of infectious tracheobronchitis (kennel cough), a prevalent, contagious respiratory infection in dogs characterized primarily by coughing, often caused by a mix of bacterial and viral agents, such as canine parainfluenza virus and Bordetella bronchiseptica. It notes the occurrence of severe, often fatal outbreaks in racing greyhounds linked to hemorrhagic pneumonia uncharacteristic of typical kennel cough. Prior to this invention, the etiology of these outbreaks was unclear, with assumptions but no definitive identification of causative agents. Additionally, challenges inherent in interspecies transmission of influenza viruses, especially establishing sustained transmission in a new host species such as dogs, are discussed, underlying the need for improved diagnostic, preventive, and therapeutic options.
The invention also discloses methods for diagnosing infection by identifying improved molecular probes, antibodies, and real-time PCR assays targeting influenza virus genes unique to canine-infecting strains. Vaccine compositions include live attenuated and inactivated formulations and recombinant viral vector constructs, with description of dosing, adjuvants, delivery systems, and administration routes. The methods can prevent, reduce the risk of, suppress, or eradicate canine influenza infection, including reduction in symptoms and virus shedding.
Claims Coverage
The patent claims describe 22 inventive features primarily relating to methods for inducing immune responses against canine influenza viruses that express mature hemagglutinin proteins with specific amino acid sequences, and compositions thereof.
Method for inducing immune response using an influenza virus with specified mature HA amino acid sequence
A method comprising administering to a canid an effective amount of a composition containing an influenza virus with a polynucleotide encoding a mature hemagglutinin (mature HA) having greater than 95% amino acid identity to SEQ ID NO: 33, with specific amino acid residues at positions 82 (serine), 221 (leucine), 327 (threonine), and 482 (threonine).
Mature HA polynucleotide encoding higher identity to SEQ ID NO: 33
A method where the polynucleotide encodes a mature HA with greater than 98% amino acid sequence identity to SEQ ID NO: 33.
Mature HA polynucleotide encoding sequence identity to SEQ ID NO: 34
A method where the polynucleotide encodes a mature HA with greater than 95% amino acid identity to SEQ ID NO: 34.
Mature HA polynucleotide encoding higher identity to SEQ ID NO: 34
A method where the polynucleotide encodes a mature HA with greater than 98% amino acid identity to SEQ ID NO: 34.
Mature HA polynucleotide encoding sequence identity to mature HA within SEQ ID NO: 62
A method where the polynucleotide encodes a mature HA having greater than 95% amino acid identity to the mature HA within SEQ ID NO: 62.
Mature HA polynucleotide encoding higher identity to mature HA within SEQ ID NO: 62
A method where the polynucleotide encodes a mature HA having greater than 98% amino acid identity to the mature HA within SEQ ID NO: 62.
Mature HA polynucleotide encoding sequence identity to mature HA within SEQ ID NO: 78
A method where the polynucleotide encodes a mature HA having greater than 95% amino acid identity to the mature HA within SEQ ID NO: 78.
Mature HA polynucleotide encoding higher identity to mature HA within SEQ ID NO: 78
A method where the polynucleotide encodes a mature HA having greater than 98% amino acid identity to the mature HA within SEQ ID NO: 78.
Use of attenuated virus
The virus administered in the method can be attenuated.
Use of inactivated virus
The virus administered in the method can be inactivated.
Virus in pharmaceutically acceptable carrier or diluent
Where the inactivated virus is provided in a pharmaceutically acceptable carrier or diluent.
Inactivation methods for virus
The virus can be inactivated by exposure to effective amounts of inactivation chemicals including formalin, beta propiolactone (BPL), binary ethylenimine (BEI), or phenol.
Use of virus in domesticated dogs
The method is applicable for administration to domesticated dogs.
Administration of virus with adjuvant
The virus can be administered to domesticated dogs together with an adjuvant.
Administration of virus in combination with other vaccines
The virus can be administered in combination with vaccines selected from bordetella vaccine, adenovirus vaccine, and parainfluenza virus vaccine.
The claims cover methods using influenza viruses with mature HA proteins having specific amino acid sequences to induce immune responses in canids, including dogs, using attenuated or inactivated viruses optionally combined with adjuvants or other vaccines. They specify the identity levels of the hemagglutinin protein sequences to known sequences and the chemical means of virus inactivation, encompassing therapeutically effective administration for prevention or treatment of canine influenza.
Stated Advantages
The vaccines and methods can prevent, reduce the risk of, delay the onset of, reduce the spread of, ameliorate, suppress, and/or eradicate influenza infection or its symptoms in canines.
The vaccines can provide a protective immune response that minimizes viral infection in host animals over time.
Use of specific vaccine compositions including inactivated or live attenuated viruses elicit significant antibody responses.
Vaccination reduces clinical signs, virus shedding, and severity of respiratory lesions caused by canine influenza virus.
Rapid, sensitive, and cost-effective diagnostic assays allow detection and monitoring of canine influenza infection.
Documented Applications
Vaccines for protecting dogs including domestic, wild, zoo, working, companion, and racing dogs from canine influenza virus infection.
Methods for inducing immune responses to canine influenza viruses using vaccines comprising equine influenza virus antigens or recombinant constructs.
Diagnostic methods to detect and identify influenza infection in animals by molecular, serological, and immunohistochemical assays.
Use of canine influenza virus isolates and polynucleotide sequences in research, vaccine development, and antiviral screening.
Animal models, including experimentally inoculated dogs, to study canine influenza virus pathogenesis and vaccine efficacy.
Kits comprising vaccines, pharamceutical compositions, administration devices, diagnostic reagents, and instructional materials for canine influenza control.
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