Drug – bio-affecting and body treating compositions – Lymphokine
Patent
1990-10-05
1992-12-08
Wax, Robert A.
Drug, bio-affecting and body treating compositions
Lymphokine
530350, 530395, 530826, 435 697, C07K 1300, A61K 39155
Patent
active
051696282
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention encompasses novel chimeric glycoproteins which are useful for preparing virus specific immune responses against human parainfluenza virus type 3, PIV3. Host cells transformed with structural genes coding for the glycoproteins, expression and replication plasmids containing the structural genes, vaccines made from the glycoproteins and methods for protecting humans by inoculation with said vaccines are also part of this invention.
BACKGROUND
Human parainfluenza virus type 3, PIV3, is an important primary cause of severe lower respiratory tract disease in infants and young children. The virus occurs worldwide and infects virtually all children under the age of four. Acute respiratory disease and secondary complications are particularly serious in infants and young children due to the immaturity of the respiratory system and may require hospitalization in severe cases. Lower respiratory infections 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. Older children and adults are also frequently reinfected although reinfection typically results in less severe upper respiratory tract illness.
Attempts to develop effective PIV3 vaccines have been largely unsuccessful. Clinical studies using live or inactivated PIV3 vaccines demonstrated an increase in virus specific serum antibodies but provided no significant protection against the disease.
INFORMATION DISCLOSURE STATEMENT
The recombinant vaccinia virus expression system is known to separately express the F and HN glycoproteins of PIV3 and to separately induce protective immune responses in challenged cotton rats, Collins, P. L., et al, Expression of the F and HN Glycoproteins of Human Parainfluenza Virus Type 3 by Recombinant Vaccinia Viruses: Contributions of the Individual Proteins to Host Immunity, Journal of Virology 61: 3416-3423 (1987). The recombinant vaccinia virus expression system is also known to induce PIV3-specific serum neutralizing antibodies and to confer resistance to PIV3 replication in the respiratory tract in primates, Collins, P. L., et al., Journal of Virology 62: 1293-1296 (1988). Immunization with a mixture of purified F and HN glycoproteins induced virus neutralizing activity and afforded complete protection from challenge infection in hamsters, Ray, R., et al., Journal of Virology 62: 783-787 (1988).
SUMMARY OF THE INVENTION
This invention encompasses a polypeptide comprising a signal sequence and at least one immunogenic fragment from both human parainfluenza virus type 3 glycoproteins F and HN. The use of this protein as a vaccine, methods to prevent PIV3-related disease and preparation of this protein using recombinant techniques are also part of this invention.
DETAILED DESCRIPTION
The following defined terms are used in this specification. The phrase "cell culture" refers to the containment of growing cells derived from either a multicellular plant or animal which allows for the cells to remain viable outside the original plant or animal. The term "downstream" identifies sequences proceeding farther in the direction of expression; for example, the coding region is downstream from the initiation codon. The term "upstream" identifies sequences proceeding in the opposite direction from expression; for example, the bacterial promoter is upstream from the transcription unit, the initiation codon is upstream from the coding region. The term "microorganism" includes both single cellular prokaryote and eukaryote organisms such as bacteria, actinomycetes and yeast. The term "operon" is a complete unit of gene expression and regulation, including structural genes, regulator genes and control elements in DNA recognized by regulator gene product. The term "plasmid" refers to an autonomous self-replicating extrachromosomal circular DNA and includes both the expression and nonexpression types. Where a recombinant microorganism or
REFERENCES:
patent: 4743553 (1088-10-01), Rice
patent: 4790987 (1988-12-01), Compans
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Spriggs, M. K., et al., "Immunization with Vaccinia Virus Recombinants that Express the Surface Glycoproteins of Human Parainfluenza Virus Type 3 (PIV3) Protects Patas Monkeys against PIV3 Infection", Journal of Virology, vol. 62 (No. 62 (No. 4):1293-1296, Apr. 1988).
Ray R., et al. "Role of Individual Glycoproteins of Human Parainfluenza Virus Type 3 in the Induction of a Protective Immune Response", Journal of Virology, vol. 62 (No. 3):783-787, (Mar. 1988).
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Ray, R., et al, "Glycoproteins of Human Parainfluenza Virus Type 3: Characterization and Evaluation as a Subunit Vaccine", The Journal of Infectious Disease, vol. 152, No. 6, pp. 1219-1230 (Dec. 1985).
Baker R. Keith
DeLuca Mark
The Upjohn Company
Wax Robert A.
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