St. Jude Children's Research Hospital

United States of America, As Represented by the Secretary of Agriculture

Icahn School of Medicine at Mount Sinai

University of Massachusetts

Mount Sinai School of Medicine

Zoetis Services LLC

New York University

Robert G Webster

Richard John Webby

Peter M Palese

Adolfo Garcia-Sastre

Kelly M Lager

Erich Hoffmann

Juergen A Richt

Elena A Govorkova

Aleksandr S Lipatov

Harriet L Robinson

Ellen F Fynan

Brian R Murphy

Robert M Chanock

Shan Lu

Nicolai V Kaverin

Virginia S Hinshaw

Mahesh Kumar

Peter Palese

Scott L Krauss

Hiroichi Ozaki

Richard J Webby

The present invention relates, in general, to attenuated swine influenza viruses having an impaired ability to antagonize the cellular interferon (IFN) response, and the use of such attenuated viruses in vaccine and pharmaceutical formulations. In particular, the invention relates to attenuated swine influenza viruses having modifications to a swine NS1 gene that diminish or eliminate the ability of the NS1 gene product to antagonize the cellular IFN response. These viruses replicate in vivo, but demonstrate decreased replication, virulence and increased attenuation, and therefore are well suited for use in live virus vaccines, and pharmaceutical formulations.

Genetically engineered swine influenza virus and uses thereof

The immunogenicity of the influenza virus hemagglutinin (HA) molecule may be increased by substitutions of amino acids in the HA sequence. The substitution of specific HA residues, such as asparagine at position 223 of H5 HA, increase the sensitivity of the hemagglutinin inhibition (HI) assay by altering receptor specificity and/or antibody-antigen binding. HA molecules containing such substitutions will be useful in the development of diagnostic reference viruses and improved influenza vaccines.

Modified influenza virus for monitoring and improving vaccine efficiency

A vaccine composition and method which is effective in preventing or ameliorating Avian Influenza Virus infection is set forth herein. The vaccine contains at least two inactivated strains of avian influenza virus, wherein the combined hemagglutinin (HA) total is at least about 200 HA/dose of the vaccine composition, and wherein each of the strains presents at least about 128 HA/dose, and further wherein one of the strains has the same HA subtype as that of a challenge virus, and wherein at least one of the strains has a different NA subtype than the challenge virus.

Avian influenza viruses, vaccines, compositions, formulations, and methods

This invention relates to a method of immunizing a vertebrate, comprising introducing into the vertebrate a DNA transcription unit which comprises DNA encoding a desired antigen or antigens. The uptake of the DNA transcription unit by a host vertebrate results in the expression of the desired antigen or antigens, thereby eliciting humoral or cell-mediated immune responses or both humoral and cell-mediated responses. The elicited humoral and cell-mediated immune response can provide protection against infection by pathogenic agents, provide an anti-tumor response, or provide contraception. The host can be any vertebrate, avian or mammal, including humans.

Immunization by inoculation of DNA transcription unit

The present invention is based on the discovery that a high titer reassortant influenza virus is produced in mammalian cell culture by replacing the NS gene of the A/PuertoRico/3/24 master strain with the NS gene of the A/England/1/53 strain. The invention provides influenza viruses and vaccines generated in mammalian cells as well as methods for producing such. The invention further provides an influenza virus master strain and kits for generating reassortant influenza viruses in mammalian cell culture and methods of making and using the master strain.

Method for generating influenza viruses and vaccines

The invention provides replication of high growth influenza virus strains, derived from clinical isolates, in cultured mammalian cells by infecting the mammalian cells with the high growth strains to obtain infected cells, and culturing the cells while maintaining a trypsin concentration range of 0.05-1.0 &mgr;g/ml in the culture medium, where the resulting replicated virus is suitable for use in mammalian influenza vaccines and vaccination methods, which are also provided by the invention.

Influenza virus replicated in mammalian cell culture and vaccine production

The present invention describes a reliably protective avian vaccine that contains a DNA transcription unit comprising a nucleic acid that encodes a viral protein. This effective and reliable avian vaccine significantly improves upon that which heretofore has been disclosed. The present invention demonstrates that the reliable efficacy found for DNA influenza vaccines, formerly observed in experimental inbred mice, can now be obtained for outbred avian species as well. Methods of use and specific DNA constructs are disclosed.

DNA transcription unit vaccines that protect against avian influenza

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Memphis, TN, United States of America

Robert G Webster