HA-specific influenza virus attenuated vaccine comprising mutations in segment 7, and uses therefor
Inventors
Kapczynski, Darrell R. • Digard, Paul • Vervelde, Lonneke • Suarez, David L.
Assignees
University of Edinburgh • US Department of Agriculture USDA
Publication Number
US-11214799-B2
Publication Date
2022-01-04
Expiration Date
2040-03-10
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Abstract
The disclosure relates to mutant recombinant influenza virus gene segment 7 with at least one mutation that modulates expression of M2 and M42 polypeptide. Also disclosed are recombinant influenza viruses comprising the mutant influenza virus gene segment 7, compositions comprising the mutant recombinant influenza virus gene segment 7, use of such mutant recombinant influenza virus gene segment 7 and mutant recombinant Influenza viruses.
Core Innovation
The invention provides mutant recombinant influenza virus gene segment 7 with at least one mutation that modulates expression of the M2 and/or M42 polypeptides. Recombinant influenza viruses comprising the mutant influenza virus gene segment 7 and compositions containing these mutants are also provided. The invention includes methods for generating these mutant gene segments and their use in influenza vaccines.
The problem addressed is the risk of reversion to virulent forms in live influenza virus vaccines and the limited immunity conferred by current vaccines, which mainly induce immunity against the hemagglutinin (HA) protein. Existing vaccines have issues such as undefined mutations, concerns about reversion to wild-type, and limitations in protection breadth. There is a need for live attenuated vaccines inducing mucosal immunity, systemic antibodies, and cellular immunity against all influenza proteins while having low pathogenicity and limited transmission potential.
Claims Coverage
The patent claims six main inventive features based on independent claims covering the vaccine composition, recombinant gene segments, cells, compositions, and their use.
HA-specific influenza virus live attenuated vaccine with segment 7 mutation
An influenza virus live attenuated vaccine comprising a mutant recombinant influenza virus gene segment 7 having either a G to C mutation at nucleotide position 52 (G52C) or a G to A mutation at nucleotide position 145 (G145A) derived from Influenza A/Chicken/Penn/1/1983. The vaccine virus does not transmit between vaccinated hosts.
Cell expressing recombinant mutant influenza virus gene segment 7
A cell selected from MDCK, Vero, CV-1, LLcomk.2, MDBK, BK-1, Chinese Hamster Ovary, 293T, human embryonic, avian embryonic, or in ovo cells, expressing the HA-specific influenza virus live attenuated vaccine containing the mutant gene segment 7 with either G52C or G145A mutations.
Composition comprising the live attenuated vaccine and adjuvant
A composition comprising the HA-specific influenza virus live attenuated vaccine with the mutant recombinant influenza virus gene segment 7 having a G52C or G145A mutation, optionally including an adjuvant.
Use of the live attenuated vaccine for treating influenza
Use of the HA-specific influenza virus live attenuated vaccine comprising a mutant recombinant influenza virus gene segment 7 with either G52C or G145A mutation for treatment of influenza in vertebrates including birds, mammals, and primates.
Recombinant influenza virus with eight viral gene segments including mutated M gene
A recombinant influenza virus comprising the PA, PB1, PB2, HA, NA, NP, NS viral gene segments and an M viral gene segment harboring either the G52C or G145A mutation compared to wild type Influenza A virus M gene segment. The vaccine virus does not transmit between vaccinated hosts.
Gene segment 7 encoding specified amino acid sequences
The gene segment 7 in the vaccine encodes amino acid sequences selected from SEQ ID NOs: 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, or 27.
The claims cover vaccines comprising mutant recombinant influenza virus gene segment 7 with specific single nucleotide mutations (G52C or G145A) that modulate M2 and/or M42 expression, characterize cells and compositions containing these mutants, and their use for immunization and treatment to prevent viral transmission between hosts.
Stated Advantages
The mutant influenza virus vaccines induce mucosal immunity, systemic antibodies, and cellular immunity against all influenza proteins, offering broader immune protection.
The recombinant viruses have low pathogenic genotype and phenotype, with limited replication and transmission potential, reducing the risk of reversion to virulence.
The live attenuated vaccines elicit robust immune responses and protect chickens against lethal challenge from highly pathogenic avian influenza viruses from both North American and Asian lineages.
Live vaccines are less costly to produce than inactivated vaccines and stimulate local mucosal immunity in the respiratory tract.
Vaccines comprising the mutant gene segments do not transmit between vaccinated hosts, enhancing safety and control of virus spread.
Documented Applications
Use of recombinant influenza virus comprising mutant gene segment 7 as live attenuated vaccines for immunizing vertebrates including birds (chickens, turkeys, waterfowl) and mammals (pigs, horses, whales, dolphins, humans) against influenza.
Vaccination of poultry to increase resistance to infection, prevent illness and death, reduce virus replication and shedding, and block virus transmission.
Preparation of recombinant influenza vaccines using sequences based on avian, canine, equine, feline, or human influenza virus gene segment 7.
Production of both live attenuated and inactivated influenza vaccines incorporating the mutant recombinant gene segment 7.
Use of vaccines for active immunization in subjects to protect against homologous and heterologous highly pathogenic influenza virus challenge from multiple lineages.
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