Immunogenic compositions comprising cold-adapted attenuated respiratory syncytial virus mutants

US6284254A · kind A · utility

Assignee

• The United States of America, as represented by the Department of Health and Human Services · US

Inventors

• Brian R. Murphy · Bethesda, US
• Robert M. Chanock · Bethesda, US
• James E. Crowe, Jr. · Nashville, US
• Mark Connors · Bethesda, US
• Kuo-Hom L. Hsu · Fort Washington, US
• Alan R. Davis · Plainwell, US
• Michael D. Lubeck · Glenmoore, US
• Bernard H. Selling · Via Enrico Fermi, US

Key dates

• Filing date: May 30, 1995
• Grant date: Sep 4, 2001
• Expiry date: May 30, 2015

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2760/18561
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

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, desi…