Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Glycoprotein – e.g. – mucins – proteoglycans – etc.
Patent
1990-06-20
1993-03-16
Schwartz, Richard A.
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
Glycoprotein, e.g., mucins, proteoglycans, etc.
4351723, 435 697, 424 89, C07K 1300, C12N 1545, C12P 2102, A61K 3702
Patent
active
051945959
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention encompasses DNA compositions encoding novel chimeric glycoproteins which are useful for preparing virus specific immune responses against human respiratory syncytial virus, HRSV. The DNA compositions include structural genes coding for the glycoproteins and expression and replication plasmids containing the structural genes. Host cells transformed with the above DNA compositions, vaccines made from the glycoproteins and methods for protecting humans by inoculation with said vaccines are also part of this invention.
BACKGROUND
HRSV was discovered in 1956 and is found worldwide. It causes upper and lower respiratory tract disease particularly in infants and young children. About 30 percent of hospitalized young children with acute respiratory disease have respiratory syncytial virus infection. In older children and adults the disease is milder. In infants this severe illness often requires hospitalization.
Infections with respiratory syncytial virus are referable to all segments of the respiratory tract, are usually associated with fever, cough, runny nose, and fatigue, and are diagnosed clinically as bronchitis, bronchiolitis, pneumonia, croup, or viral infection. In older children and adults the virus is generally limited to replication in the upper respiratory tract. Infants may be more severely involved when the virus extends into the lungs. Lung damage can be permanent.
Primary infection with respiratory syncytial virus occurs early in life, usually before 4 years of age. Among children, illness caused by this virus tends to occur at least once each year in rather sharply defined outbreaks of several months duration. Epidemics are sharply circumscribed, generally for 3 to 5 months. In family studies, children in early school years frequently introduce the virus into the home, infecting younger members of the family more severely than other family members. The clinical consequence of infection is most severe on first experience and becomes milder in older individuals who are immunologically experienced.
Secondary effects of respiratory syncytial virus can range from inapparent infection to severe pneumonia and death. Inflammation of the respiratory tract is responsible for most symptoms. Complete recovery in most cases occurs in one to three weeks with the production of antibody which appears to persist throughout life. In the United States about 30 percent of 1-year-old infants and 95 percent of 5-year-old children have circulating respiratory syncytial virus antibody. Reinfections in older infants, children, and adults with antibody are mostly mild upper respiratory illnesses in the form of colds.
Although low yields of virus in cell culture have hindered HRSV research, the virus has been well studied. HRSV is a paramyxovirus containing a single negative strand of RNA which is transcribed into 10 predominantly monocistronic messengers. The messengers have been isolated and translated in vitro. The products have been characterized by gel electrophoresis, peptide mapping and immuno-precipitation as being similar to structural proteins isolated from virions. The structural proteins include a major nucleocapsid protein (N; MW ca. 42,000), a nucleocapsid phosphoprotein (P; MW ca. 34,000), a large nucleocapsid protein (L; MW ca. 200,000), an envelope matrix protein (M; MW ca. 26,000), a matrix glycoprotein (ca. 22,000) and two envelope glycoproteins, the fusion glycoprotein (F; MW ca. 68,000 to 70,000) and a second, methionine poor glycoprotein (G; MW ca. 84,000 to 90,000). In addition, a virally encoded protein of about 9,500 daltons and other small proteins are known to be present in infected cells, Collins, et al., Identification of a tenth mRNA of HRSV and assignment of polypeptides to the 10 viral genes, J. of Virol. 49:572-578 (1984) and references cited therein. Additional work describing the molecular biology of HSRV includes: (1) Collins, et al., Nucleotide Sequence of the gene encoding the fusion (F) glycoprotein of human respiratory syncytial virus, Proc.
REFERENCES:
patent: 4855224 (1989-08-01), Berman et al.
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Ball, L. A., et al., "Expression of the Major Glycoprotein G of Human Respiratory Syncytial Virus from Recombinant Vaccinia Virus Vectors", Jan. 1986, Proc. Natl. Acad. Sci. U.S.A., 83:246-250.
Olmstead, R. A., et al., "Expression of the F Glycoprotein of Respiratory Syncytial Virus by a Recombinant Vaccinia Virus: Comparison of the Individual Contributions of the F and G Glycoproteins to Host Immunity", Oct. 1986, Proc. Natl. Acad. Sci. U.S.A., 83:7462-7466.
Stott, E. J., et al., "Human Respiratory Syncytial Virus Glycoprotein G Expressed from a Recombinant Vaccinia Virus Vector Protects Mice Against Live-Virus Challenge", Nov. 1986, J. Virol. 60(2):607-613.
Walsh, E. E., et al., "Immunization with Glycoprotein Subunits of Respiratory Syncytial Virus to Protect Cotton Rats Against Viral Infection", Jun. 1987, J. Infect. Dis. 155(6):1198-1204.
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Elango, N., et al., "Resistance to Human Respiratory Syncytial Virus (RSV) Infection Induced by Immunization of Cotton Rats with a Recombinant Vaccinia Virus Expressing the RSV G Glycoprotein", Mar. 1986, Proc. Natl. Acad. Sci. U.S.A., 83:1906-1910.
Wertz, G. W., et al., "Nucleotide Sequence of the G Protein Gene of Human Respiratory Syncytial Virus Reveals an Unusual Type of Viral Membrane Protein", Jun. 1985, Proc. Natl. Acad. Sci. U.S.A. 82:4075-4079.
Johnson, Jr., R. J., et al., "Antigenic Relatedness Between Glycoproteins of Human Respiratory Syncytial Virus Subgroups A and B: Evaluation of the Contributions of F and G Glycoproteins to Immunity", Oct. 1987, J. Virol. 61(10):3163-3166.
Moss, B., "Vaccine Against Respiratory Syncytial Virus is Recombinant Vaccinia Virus Esp. Vaccinia-RSV G and F Glycoprotein Viruses", 26 Aug. 1986, Dialog Information Services, File 351, World Patent Index 81-89, Dialog Accession No. 4,315,328, U.S. 6,849,299, A.
Collins et al., PNAS vol. 81, 1984, pp. 7683-7687.
Corneglio Donald
DeLuca Mark
Ketter James
Schwartz Richard A.
The Upjohn Company
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