The Scripps Research Institute

Intracel Resources LLC

The United States of America, as Represented by the Secretary, Department of Health and Human Services

American Home Products Corporation

The United States of America as Represented by the Department of Health

The United States of America

James E Crowe, Jr

Brian R Murphy

Robert M Chanock

Dennis R Burton

Carlos F Barbas, Iii

Mark Connors

Alan R Davis

Michael D Lubeck

Kuo-Hom L Hsu

Glenn R Pilkington

Bernard H Selling

Page S Gilmour

The present invention relates to the identification and cloning of a novel neutralizing human monoclonal antibody to the Respiratory Syncytial Virus. The invention provides such antibodies, fragments of such antibodies retaining RSV-binding ability, chimeric antibodies retaining RSV-binding ability, and pharmaceutical compositions including such antibodies. The invention further provides for isolated nucleic acids encoding the antibodies of the invention and host cells transformed therewith. Finally, the invention provides for diagnostic and therapeutic methods employing the antibodies and nucleic acids of the invention.

Neutralizing monoclonal antibodies to respiratory syncytial virus

Human monoclonal antibodies and fragments thereof which bind, neutralize and provide passive immunotherapy to respiratory syncytial virus (RSV) antigenic subgroups A and B are disclosed. Also disclosed are diagnostic and immunotherapeutic methods of using the monoclonal antibodies as well as cell line producing the monoclonal antibodies.

Human neutralizing monoclonal antibodies to respiratory syncytial virus

A method for providing passive immmunotherapy to respiratory syncytial virus (RSV) disease in a host is disclosed. The method includes administering to a host a human monoclonal antibody Fab fragment that neutralizes both antigenic subgroup A and subgroup B of respiratory syncytial virus (RSV), or a monoclonal antibody comprising the fragment.

The respiratory syncytial virus (RSV) is a major cause of lower respiratory tract disease in infants and children throughout the world. RSV is a major cause of pneumonia and bronchiolitis in infants under one year of age, and is a major cause of fatal respiratory tract disease in these infants. The treatment and prevention of RSV infection has been problematic. However, the present invention addresses some of these concerns by providing attenuated RSV strains that are suitable for inclusion in immunizing compositions. Specifically, the present invention is directed toward the introduction of growth restriction mutations into incompletely attenuated host range-restricted cold-passaged respiratory syncytial virus (cpRSV) strains by further passage of the strains at increasingly reduced temperatures to produce derivative strains which are more satisfactorily attenuated. These cold-adaptation (ca) approaches were used to introduce further attenuation in the parental RSV virus cpRSV-3131, which is incompletely attenuated in seronegative children. Mutants of the parental strain were obtained by selecting for large plaque production at reduced temperatures. An RSV cp-3131 derivative, designated D,, was isolated that produces large plaques at 25&deg; C. Biologically cloned virus D1 produces distinctly and uniformly larger plaques at 25&deg; C. as compared to the parental attenuated strain cpRSV-3131 or wild-type strain A2. Thus, D1 is an attenuated cold-adapted, but not temperature-sensitive, RSV mutant. The invention also provides methods for stimulating RSV-specific immune responses in an individual through the administration of said mutants.

Immunogenic compositions comprising cold-adapted attenuated respiratory syncytial virus mutants

The present invention provides vaccine compositions of attenuated respiratory syncytial virus (RSV). More particularly, the attenuated virus may be a derivative of RSV which has been incompletely attenuated by cold-passage or introduction of mutations which produce virus having a temperature sensitive (ts) or cold adapted (ca) phenotype. The invention also provides methods for stimulating the immune system of an individual to induce protection against respiratory syncytial virus by administration of attenuated RSV. The invention also provides pure cultures of attenuated RS virus, wherein the virus has been more completely attenuated by the further derivatization of previously identified incompletely attenuated ts or cp mutants.

Attenuated respiratory syncytial virus vaccine compositions

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Chevy Chase, MD, United States of America

James E Crowe, Jr