St. Jude Children's Research Hospital

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

Icahn School of Medicine at Mount Sinai

Leland Stanford Junior University

Mount Sinai School of Medicine

Zoetis Services LLC

Richard John Webby

Robert G Webster

Peter M Palese

Adolfo Garcia-Sastre

Kelly M Lager

Erich Hoffmann

Juergen A Richt

Aleksandr S Lipatov

Elena A Govorkova

Mahesh Kumar

Steven K Foung

Zhen-Yong Keck

Scott L Krauss

Hiroichi Ozaki

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

A panel of IgGhuman monoclonal antibodies (HMAbs) identified by hemagglutination inhibition (HI) assay has been produced from peripheral B cells of an individual immunized with prototype H5N1 vaccine. Sequence analysis of antibody clones showed three clusters of different HMAbs as represented by HMAbs designated as BF1-1, BF1-19 and BF1-10. BF1-1 and BF1-10 have distinct CDR 1, 2 and 3 regions of both heavy and light chains. BF1-19 has the same heavy chain as BF1-1 but the light chain of BF1-10. Antibody binding affinity, K, studies showed all three HMAbs ranging from at least about 10to at least about 10. In vivo protection studies showed that these antibodies afforded significant protection against infection. These findings demonstrate that the antibodies of the invention are cross-neutralizing and therapeutic.

Human neutralizing monoclonal antibodies to H5N1 influenza A virus

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

Growing community of inventors

Memphis, TN, United States of America

Richard John Webby