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AssigneeThe United States of America as represented by the Department of Health and Human Services
InventorsBrian R. Murphy, Peter L. Collins, Stephen S. Whitehead, Alexander A. Bukreyev, Katalin Juhasz, Michael N. Teng
Estimating the term…
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.
An isolated infectious recombinant respiratory syncytial virus (RSV) comprising a RSV genome or antigenome, a major nucleocapsid (N) protein, a nucleocapsid phosphoprotein (P), a large polymerase protein (L), and a RNA polymerase elongation factor, wherein the recombinant RSV has at least two attenuating mutations, one of the mutations specifying a temperature-sensitive substitution at amino acid Phe.sub.521, Gln.sub.831, Met.sub.1169, or Tyr.sub.1321 in the RSV polymerase gene or a temperature-sensitive nucleotide substitution in the gene-start sequence of gene M2, and wherein said recombinant RSV has one or more recombinant modifications selected from (i) multiple nucleotide changes in a codon specifying the temperature sensitive substitution, (ii) a restriction marker;
The RSV of 6, wherein the temperature-sensitive substitutions are at Gln.sub.831 and Tyr.sub.1321.
A composition which comprises an expression vector comprising an isolated polynucleotide molecule encoding a RSV genome or antigenome having at least two attenuating mutations, at least one of the mutations specifying a temperature-sensitive substitution at amino acid Phe.sub.521, Gln.sub.831, Met.sub.1169, or Tyr.sub.1321 in the RSV polymerase gene or a temperature-sensitive nucleotide substitution in the gene-start sequence of gene M2, and one or more expression vectors which comprise one or more polynucleotide molecules encoding N, P, L and RNA polymerase elongation factor proteins of RSV, whereby upon expression an infectious RSV particle is produced.
Dependencies are inferred from the claim text.