Provided are compounds of Formula III that enhance the efficacy of viruses by increasing spread of the virus in cells, increasing the titer of virus in cells, or increasing the antigen expression from a virus, gene or trans-gene expression from a virus, or virus protein expression in cells. Other uses, compositions and methods of using same are also provided. ##STR00001##

An isolated recombinant influenza virus is provided having PA, PB1, PB2, NP, NS, M, NA and HA viral segments, wherein the PB1 viral segment encodes a PB1 with a residue other than isoleucine at position 711 or the M viral segment encodes a M1 with a residue other than methionine at position 128, wherein the recombinant influenza virus has enhanced replication relative to a corresponding influenza virus having a PB1 viral segment that encodes a PB1 with an isoleucine at position 711 or having a M viral segment that encodes a M1 with methionine at position 128, as well as methods of making and using the virus.

The present invention provides a method for purification of a virus or virus antigen comprising providing a virus preparation and centrifugation of said virus preparation in a gradient of a sugar established by the addition of two or more buffered sugar layers of different concentration. The method leads to higher yields and reduces unwanted aggregation of the virus or virus antigen by increasing the volume of the peak pool.

New influenza donor strains for the production of reassortant influenza A viruses are provided.

The present invention relates to the microbial immunogens engineered to bear -gal epitope(s) for induction of potent humoral and cellular immune responses when administered to subjects having anti-Gal antibodies. In one embodiment, the present invention provides compositions and methods for propagating influenza virus in human, ape, Old World monkey or bird cells that have been engineered to express an 1,3galactosyltransferase ( 1,3GT) gene to produce virions bearing hemagglutinin molecules containing -gal epitopes, to increase the immunogenicity of the influenza virus. In another embodiment, the present invention provides fusion proteins between influenza virus hemagglutinin and a microbial peptide or protein of interest, and enzymatic processing of this fusion protein to carry -gal epitopes, to increase the immunogenicity of the microbial peptide or protein of interest.

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.

The present application provides an attenuated orthomyxovirus-based (e.g., influenza A virus (IAV)-based) replicon vector, which optionally encodes a biological cargo, and in which the one or more envelope glycoprotein transcripts are engineered to comprise one or more miRNA Silencing Elements (MSEs) such that the one or more vector envelope glycoproteins are expressed in a first cell type or species, but are not expressed in a second cell type or species, wherein the introduction of the attenuated replicon vector into the second cell type or species results in a sustained production of the biological cargo in the absence of vector propagation and cell death and/or toxicity. In other aspects, the present application is directed to the attenuated replicon vector production and its use for sustained production of biological cargo in vivo and prevention and treatment of diseases.

New influenza donor strains for the production of reassortant influenza A viruses are provided.

The invention provides compositions and methods useful to prepare segmented, negative strand RNA viruses, e.g., orthomyxoviruses such as influenza A viruses, entirely from cloned cDNAs and in the absence of helper virus.

The present invention relates to the microbial immunogens engineered to bear -gal epitope(s) for induction of potent humoral and cellular immune responses when administered to subjects having anti-Gal antibodies. In one embodiment, the present invention provides compositions and methods for propagating influenza virus in human, ape, Old World monkey or bird cells that have been engineered to express an 1,3galactosyltransferase ( 1,3GT) gene to produce virions bearing hemagglutinin molecules containing -gal epitopes, to increase the immunogenicity of the influenza virus. In another embodiment, the present invention provides fusion proteins between influenza virus hemagglutinin and a microbial peptide or protein of interest, and enzymatic processing of this fusion protein to carry -gal epitopes, to increase the immunogenicity of the microbial peptide or protein of interest.