Influenza virus vectors and uses therefor

Inventors

LeFebvre, Matthew Frederick • Hatta, Yasuko • Bilsel, Pamuk • Moser, Michael J.

Assignees

FluGen Inc

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 relates to mutant influenza viral vectors that are M2-defective for antigen delivery and vaccination. The concept is based on M2 knockout conditions in which no functional M2 expression occurs, and on stability against reversion. Foreign antigen coding sequences are introduced such that the composition produces immune responses while maintaining the mutant M2 viral characteristics.

In particular, the disclosure describes nucleic acid sequences including SEQ ID NO:35, with SEQ ID NO:35 further comprising nucleic acid encoding one or more foreign antigens, and recombinant influenza virus/vaccine constructs that include these sequences. The vectors are configured for antigen expression, with the foreign antigens described as pathogen-derived antigens and tumor-derived antigens in the context of immunogenic compositions.

The mutant influenza vectors are supported by findings showing restricted replication compared with replication in normal conditions, attenuation of pathogenicity in mice, and induction of humoral and mucosal immunogenicity. The disclosure further states protection against lethal challenge and describes non-replication or dissemination and lack of transmission in a ferret model, along with intradermal delivery using microneedle devices.

Claims Coverage

The independent claims cover two inventive features: an immunogenic composition defined by SEQ ID NO:35 with foreign antigen encoding, and a vaccine preparation method using a bioreactor and viral propagation of a recombinant virus carrying the nucleic acid sequence of claim 1.

The claims center on a vaccine system defined by an immunogenic composition containing SEQ ID NO:35 with nucleic acid encoding foreign antigens, and on a method for preparing a vaccine by propagating a recombinant virus in a bioreactor, isolating progeny virus particles, and formulating for administration.

Stated Advantages

Documented Applications