Production of attenuated respiratory syncytial virus vaccines fr

Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Virus or component thereof

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4242041, 4242051, 435 693, 435236, 4353201, A61K 39155, C12N 704, C12N 1500

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active

059938242

ABSTRACT:
Attenuated respiratory syncytial virus (RSV) and vaccine compositions thereof are produced by introducing specific mutations associated with attenuating phenotypes into wild-type or RSV which is incompletely attenuated by cold-passage or introduction of mutations which produce virus having a temperature sensitive (ts) or cold adapted (ca) phenotype. Alternatively, recombinant RSV and vaccine compositions thereof incorporate attenuating and other mutations specifying desired structural and or phenotypic characteristics in an infectious RSV. Recombinant RSV incorporate desired mutations specified by insertion, deletion, substitution or rearrangement of a selected nucleotide sequence, gene, or gene segment in an infectious RSV clone. The immune system of an individual is stimulated to induce protection against natural RSV infection, or multivalently against infection by RSV and another pathogen, such as PIV, by administration of attenuated, biologically derived or recombinant RSV.

REFERENCES:
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Connors et al., "A Cold-Passaged, Attenuated Strain of Human Respiratory Syncytial Virus Contains Mutations in the F and L Genes," Virology 208:478-484 (1995).
Firestone et al., "Nucleotide Sequence Analysis of the Respiratory Syncytial Virus Sugroup A Cold-Passaged (cp) Temperature Sensitive (ts) cpts-248/404 Live Attenuated Virus Vaccine Candidate," Virology 225:419-422 (1996).
Crowe, Jr., et al., "Acquisition of the ts Phenotype by a Chemically Mutagenized Cold-passaged Human Respiratory Syncytial Virus Vaccine Candidate Results from the Acquisition of a Single Mutation in the Polymerase (L) Gene," Virus Genes 13:269-273 (1996).
Crowe, et al., "A further attenuated derivative of a cold-passaged temperature-sensitive mutant of human respiratory syncytial viurs retains immunogenecity and protective efficacy agains wild-type challenge in seronegative chimpanzees", Vaccine, vol. 12, 1994.
Wathen et al., "Characterizaton of a novel human respiratory syncytial virus chimeric FG glycoprotein expressed using a baculovirus vector", J. Gen. Virol., vol. 70, pp. 2625-2635, 1989.

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