Influenza virus vectors and uses therefor
Inventors
LeFebvre, Matthew Frederick • Hatta, Yasuko • Bilsel, Pamuk • Moser, Michael J.
Assignees
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Publication Number
US-11253584-B2
Publication Date
2022-02-22
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 a mutant M2 sequence, and are useful in immunogenic compositions, e.g., as vaccines. The mutant viruses disclosed herein including a mutant M2 sequence are also useful to deliver antigens to a subject, e.g., to induce an immune response to the antigen. 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 a nucleic acid sequence comprising SEQ ID NO:35, wherein SEQ ID NO:35 further comprises a nucleic acid sequence encoding one or more antigens. The nucleic acid is supported as a component of immunogenic compositions and vaccine formulations, and as a component of a recombinant influenza virus in an influenza-based system.
The document further provides influenza viral vectors and recombinant influenza viruses that use mutant influenza (M2) biology. Influenza M2 mutants are described as lacking M2 ion channel function, showing attenuated and replication-restricted behavior, and remaining stable without reversion in defined propagation contexts.
The described approach includes compositions and methods for immunization and immune response elicitation in a subject using influenza viral vectors carrying nucleic acid encoding one or more antigens. The disclosure also describes intranasal influenza vaccination in ferrets, prime and prime/boost regimens, viral shedding via nasal washes, antibody responses via IgA/IgG assays, adverse event assessment related to vaccination, and protection readouts after challenge.
Claims Coverage
The independent claims cover two inventive features: a nucleic acid sequence comprising SEQ ID NO:35 that encodes one or more antigens, and a method for eliciting an immune response by administering an influenza viral vector containing antigen-encoding nucleic acid within specified SEQ ID configurations.
Nucleic acid comprising SEQ ID NO:35 encoding one or more antigens
A nucleic acid sequence comprising SEQ ID NO:35, wherein SEQ ID NO:35 further comprises a nucleic acid sequence encoding one or more antigens.
Influenza viral vector with antigen-encoding nucleic acid and specified SEQ ID configurations
A method for eliciting an immune response in a subject, comprising administering to the subject an influenza viral vector, wherein the influenza viral vector comprises nucleic acid encoding one or more antigens, wherein the virus comprises SEQ ID NO:1, SEQ ID NO:34, or SEQ ID NO:35.
Overall, the claims emphasize antigen-encoding nucleic acids that include SEQ ID NO:35 and methods that administer influenza viral vectors containing antigen-encoding nucleic acid within specified SEQ ID configurations to elicit immune responses.
Stated Advantages
M2KO(ΔTM) causes no clinical signs in the respiratory tract of ferrets.
M2KO(ΔTM) causes no histopathology signs in the respiratory tract of ferrets.
M2KO(ΔTM) shows limited or none replication in harvested respiratory organs.
M2KO(ΔTM) is suitable for intranasal influenza vaccination.
The document reports protection readouts after vaccination with M2KO(ΔTM) regimens.
M2 mutants lack M2 ion channel function and show attenuated and replication-restricted behavior.
M2 mutants remain stable without reversion in defined propagation contexts.
The immune response is elicited in a subject by administering the influenza viral vector comprising antigen-encoding nucleic acid.
Documented Applications
Intranasal influenza vaccination using M2KO(ΔTM) in ferrets, including prime and prime/boost regimens and subsequent protection readouts after challenge.
Eliciting immune responses in subjects by administering influenza viral vectors comprising nucleic acid encoding one or more antigens, including measurement of antibody responses such as nasal wash viral shedding and IgA/IgG responses.
Transmission studies in ferrets to assess whether M2KO(ΔTM) transmits to contact ferrets via direct contact or aerosol.
Immunizing a subject by administering a composition containing a recombinant influenza virus having the nucleic acid sequence of SEQ ID NO:35.
Immunogenicity and protection evaluation in murine examples after intranasal immunization, including protection against lethal homosubtypic and heterosubtypic challenges and comparative efficacy versus FluMist/Fluzone.
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