Immunogenic compositions against influenza
Inventors
Moser, Michael J. • Hatta, Yasuko • Bilsel, Pamuk
Assignees
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Publication Number
US-11344616-B2
Publication Date
2022-05-31
Expiration Date
Abstract
Disclosed herein are compositions and methods related to mutant viruses, and in particular, mutant influenza viruses. The mutant viruses disclosed herein include mutant M2 sequences, mutant BM2 sequences, and are useful in immunogenic compositions, e.g., as a quadrivalent vaccines. Also disclosed herein are methods, compositions and cells for propagating the viral mutants, and methods, devices and compositions related to vaccination.
Core Innovation
The invention relates to an influenza immunogenic system using a multivalent immunogenic composition that includes recombinant viruses from at least two influenza strains. The multivalent composition comprises at least one engineered attenuated influenza A M2-deficient recombinant virus and at least one engineered attenuated influenza B BM2-deficient recombinant virus, each engineered to lack functional M2 or BM2 ion-channel activity.
In one described format, the composition is a quadrivalent formulation that combines engineered attenuated influenza A viruses representing H1N1 and H3N2 subtypes with engineered attenuated influenza B viruses representing the B/Yamagata and B/Victoria lineages. The system uses recombinant single-replication viruses lacking functional M2 and BM2 ion-channel activity, and the composition may further include a pharmaceutically acceptable carrier and/or a pharmaceutically acceptable adjuvant.
The documented immunological outcome is that quadrivalent formulations elicit anti-HA IgG responses and hemagglutination inhibition activity against both influenza A and influenza B components without component interference. The system is also described as providing protection in mice and ferrets against lethal homologous and heterologous influenza challenge, with reduced viral titers and weight loss/clearance depending on antigen match.
Claims Coverage
The document includes two independent claims. The claim scope centers on a multivalent immunogenic composition and a method of stimulating an immune response against influenza A and influenza B by administering that composition, with shared inventive features of recombinant engineered attenuated influenza A M2-deficient viruses and recombinant engineered attenuated influenza B BM2-deficient viruses defined by specific mutant gene SEQ ID ranges.
Multivalent recombinant influenza immunogenic composition with engineered attenuated M2-deficient influenza A and BM2-deficient influenza B
A multivalent composition comprising at least one engineered attenuated influenza A M2-deficient recombinant virus and at least one engineered attenuated influenza BM2-deficient recombinant virus, where the engineered influenza A virus comprises a mutant M2 gene comprising SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3, and the engineered influenza B virus comprises a mutant BM2 gene comprising SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, or SEQ ID NO: 11.
Method for stimulating immune response to influenza A and influenza B using the multivalent engineered M2/BM2-deficient composition
A method of stimulating an immune response against influenza A and influenza B comprising administering to a subject in need thereof a multivalent immunogenic composition comprising at least one engineered attenuated influenza A M2-deficient recombinant virus and at least one engineered attenuated influenza BM2-deficient recombinant virus, with the same SEQ ID-defined mutant M2 and BM2 genes.
Across both independent claims, the claim scope centers on a multivalent immunogenic composition that includes recombinant engineered attenuated influenza A M2-deficient viruses and recombinant engineered attenuated influenza B BM2-deficient viruses, with a corresponding method of administering this composition to stimulate immune responses to both influenza A and influenza B.
Stated Advantages
Elicits anti-HA IgG responses and hemagglutination inhibition activity against both influenza A and influenza B components without component interference.
Provides protection in mice and ferrets against lethal homologous and heterologous influenza challenge with reduced viral titers and weight loss/clearance depending on antigen match.
Documented Applications
Immunogenic compositions and corresponding administration methods for stimulating immune responses against influenza A and influenza B in a subject in need thereof.
Quadrivalent vaccine formulations for influenza A including H1N1 and H3N2 and influenza B including B/Yamagata and B/Victoria, evaluated in mice and ferrets with homologous and heterologous influenza challenge.
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