Immunogenic compositions against influenza

Inventors

Moser, Michael J. • Hatta, Yasuko • Bilsel, Pamuk

Assignees

FluGen Inc

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Publication Number

US-12311020-B2

Patent

Publication Date

2025-05-27

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 disclosure describes mutant influenza A single-replication recombinant viruses and mutant influenza B single-replication recombinant viruses. For influenza A, the viruses are M2-deficient and include mutant M2 gene sequences referenced as SEQ ID NOs (M2SR, SEQ ID NOs 1–3). For influenza B, the viruses are BM2-deficient and include mutant BM2 gene sequences referenced as SEQ ID NOs (BM2SR, SEQ ID NOs 6–11).

The invention provides multivalent vaccine compositions that combine engineered influenza A subtypes and influenza B lineages. The compositions are described as quadrivalent formulations including engineered attenuated influenza A viruses comprising H1N1 and H3N2 and engineered attenuated influenza B viruses comprising B/Victoria and B/Yamagata. Each virus is defined by a specific mutant M2 or BM2 gene sequence identifier.

The document further describes concepts for vaccine use, including pharmaceutically acceptable carriers/adjuvants and formulated delivery options. It describes delivery including intranasal or intracutaneous administration, including references to devices for intracutaneous delivery. The disclosure also positions the SR vaccine mechanism versus conventional attenuated/live vaccines, and provides characterization of immune responses and cross-protection in animal challenge models.

Claims Coverage

The partial content includes four independent claims that cover quadrivalent immunogenic compositions with defined engineered attenuated influenza A and B virus components, and methods of stimulating an immune response by administering the defined quadrivalent immunogenic compositions. The inventive features center on the specific quadrivalent virus/genetic composition and, in dependent refinements, formulation and administration route options.

Quadrivalent composition with engineered attenuated influenza A and mutant M2 SEQ ID NO: 1

An immunogenic composition that is a quadrivalent composition consisting of two engineered attenuated influenza A viruses, H1N1 having a mutant M2 gene comprising SEQ ID NO: 1 and H3N2 having a mutant M2 gene comprising SEQ ID NO: 1.

Quadrivalent composition with engineered attenuated influenza B and mutant BM2 SEQ ID NO: 9

An immunogenic composition that is a quadrivalent composition consisting of two engineered attenuated influenza B viruses, B/Victoria having a mutant BM2 gene comprising SEQ ID NO: 9 and B/Yamagata having a mutant BM2 gene comprising SEQ ID NO: 9.

Quadrivalent composition with engineered attenuated influenza A and mutant M2 SEQ ID NO: 1 plus engineered attenuated influenza B and mutant BM2 SEQ ID NO: 11

An immunogenic composition that is a quadrivalent composition consisting of two engineered attenuated influenza A viruses, H1N1 having a mutant M2 gene comprising SEQ ID NO: 1 and H3N2 having a mutant M2 gene comprising SEQ ID NO: 1, and two engineered attenuated influenza B viruses, B/Victoria having a mutant BM2 gene comprising SEQ ID NO: 11 and B/Yamagata having a mutant BM2 gene comprising SEQ ID NO: 11.

Method of stimulating an immune response with quadrivalent composition containing engineered attenuated influenza A and influenza B defined by mutant M2/BM2 gene sequences

A method of stimulating an immune response against influenza A and influenza B comprising administering to a subject a quadrivalent immunogenic composition consisting of two engineered attenuated influenza A viruses and two engineered attenuated influenza B viruses defined by mutant M2 and BM2 gene sequences.

Across the independent claims shown, the claim coverage centers on quadrivalent immunogenic compositions comprising specifically engineered attenuated influenza A viruses and specifically engineered attenuated influenza B viruses with mutant M2 and BM2 gene sequences. The related independent method claims cover administering these quadrivalent compositions to stimulate immune responses against influenza A and influenza B.

Stated Advantages

Lack of interference in multivalent formulations.

Reduced viral replication in challenge models.

Documented Applications

Vaccine use to stimulate immune responses against influenza A and influenza B by administering a quadrivalent immunogenic composition.

Animal challenge model evaluation including antibody responses and cross-protection/survival in mice and ferrets challenged with influenza A/B.

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