Recombinant vectors expressing antigens of avian influenza virus and uses thereof
Inventors
Mebatsion, Teshome • Pritchard, Joyce • Swayne, David
Assignees
US Department of Agriculture USDA • Boehringer Ingelheim Animal Health USA Inc
Publication Number
US-11058761-B2
Publication Date
2021-07-13
Expiration Date
2037-10-20
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
The present invention provides recombinant viral vectors that contain and express antigens of avian pathogens, compositions comprising the recombinant viral vectors, polyvalent vaccines comprising the recombinant viral vectors. The present invention further provides methods of vaccination against a variety of avian pathogens and method of producing the recombinant viral vectors.
Core Innovation
The invention provides recombinant viral vectors comprising one or more heterologous polynucleotides coding for and expressing at least one antigen of an avian pathogen, specifically avian influenza virus (AIV) antigens such as hemagglutinin (HA). These recombinant vectors include herpesvirus of turkeys (HVT) and fowlpox virus (FPV) vectors. The invention also discloses compositions or vaccines comprising these recombinant viral vectors, including polyvalent vaccines containing multiple vectors expressing different avian pathogen antigens.
The recombinant viral vectors are designed to express HA antigens optimized for immunogenicity, including modifications at the cleavage site to alter pathogenicity. The vectors bear heterologous polynucleotides inserted at specific non-essential genomic loci, with expression driven by various strong promoters such as SV40, mCMV, HHV3gB, or vaccinia H6 promoters. Methods of vaccination employing these recombinant vectors, including prime-boost regimens using HVT and FPV vectors, are also provided.
The problem addressed arises from the global economic and health impact of avian influenza virus infection, including the highly pathogenic H5N1 and H5N2 subtypes, which cause significant mortality in poultry and pose potential pandemic threats. Current influenza vaccines face challenges due to the antigenic variability of influenza viruses and the need for effective immunization strategies to protect susceptible avian species. Therefore, there is a need for novel, safe, and effective vaccine vectors expressing AIV antigens to prevent avian influenza infections in birds.
Claims Coverage
The patent contains multiple independent claims focused on compositions and recombinant viral vectors expressing avian influenza virus antigens, particularly HA antigens, and methods of vaccination using these compositions or vectors.
Composition or vaccine comprising recombinant HVT viral vectors expressing avian influenza HA antigen
A composition or vaccine containing one or more recombinant herpesvirus of turkeys (HVT) viral vectors, where at least one vector carries one or more heterologous polynucleotides coding for and expressing at least one avian influenza virus antigen, specifically an HA antigen. The HA antigen polynucleotide encodes amino acid sequences as specified by SEQ ID NOs: 2, 4, 20-28 or with at least 75% sequence identity to nucleotide sequences SEQ ID NO:1, 3, or 99% identity to amino acid SEQ ID NO:17.
Polynucleotide regulatory elements and insertion loci for improved expression
The HA antigen polynucleotide is operably linked to selected promoters from a group including immediate early cytomegalovirus (CMV), SV40, Human Herpesvirus Type III glycoprotein B (HHV3gB), vaccinia H6, and others. The polynucleotide is inserted into defined non-essential loci of the HVT genome such as the IG1 (UL55), IG2, IG3, UL43, US10, or SORF3/US2 loci.
Inclusion of mutated HA cleavage region for modification of antigen properties
The HA antigen includes a mutated cleavage site region with a specific amino acid sequence set forth in SEQ ID NO:15 to modify pathogenic characteristics.
Polyvalent vaccine compositions with multiple recombinant viral vectors
Vaccines may further comprise a second viral vector, either HVT or FPV, also expressing avian influenza virus antigen(s), potentially including HA antigens with specified sequence identities, for polyvalent protection.
Recombinant herpesvirus of turkeys (HVT) viral vector expressing avian influenza HA antigen
A recombinant HVT vector with one or more heterologous polynucleotides encoding an avian influenza HA antigen with sequences as specified or at least 75% nucleotide or 99% amino acid identity to identified SEQ ID NOs, operably linked to strong promoters and inserted into defined loci to ensure viable virus and antigen expression.
Method of vaccinating an animal including prime-boost regimens
A method to vaccinate animals or induce immunogenic or protective responses against avian influenza by administering at least one dose of the disclosed compositions or recombinant vectors, including regimes where prime and boost administrations may involve the same or different viral vectors selected from HVT and FPV.
Recombinant fowlpox virus (FPV) vector expressing avian influenza HA antigen
A recombinant FPV viral vector harboring heterologous polynucleotides encoding avian influenza HA antigen sequences, operably linked to promoters such as vaccinia H6, inserted into FPV genome loci including F7 and F8, with modifications including the mutated HA cleavage region.
The claims cover compositions and recombinant viral vectors using herpesvirus of turkeys and fowlpox virus to express avian influenza HA antigens with specific sequence identities and regulatory elements. These vectors are designed for safe and effective vaccination methods including polyvalent vaccines and prime-boost regimens against avian influenza pathogens.
Stated Advantages
Recombinant viral vectors expressing modified HA proteins provide better protection in avian species than vectors expressing mutant HA proteins.
Polyvalent compositions or vaccines comprising multiple recombinant viral vectors effectively protect animals against a variety of avian pathogens without interference.
The vectors allow for stable expression of antigens and are free from detectable parental viruses, ensuring safety and consistency.
Vaccines based on these vectors reduce viral shedding post-challenge, enhancing disease control and limiting transmission risk.
Use of various promoters and optimized insertion sites enables high-level antigen expression to induce robust immune responses.
Documented Applications
Vaccination of avian species, including chickens and turkeys, against avian influenza virus infections using recombinant HVT and FPV viral vectors expressing HA antigens.
Use in prime-boost immunization regimens combining HVT and FPV vectors or sequential administrations to enhance immune responses in birds.
Production of polyvalent vaccines incorporating multiple recombinant viral vectors expressing different avian pathogen antigens for broad protection.
Immunization of broiler chickens with maternally derived antibodies to overcome maternal antibody interference by prime-boost strategies involving HVT and recombinant Newcastle Disease Virus (rNDV) vaccines.
Interested in licensing this patent?