Recombinant parainfluenza virus vaccines attenuated by deletion or ablation of a non-essential gene

US6410023B1 · kind B1 · utility

Assignee

• The United States of America · US

Inventors

• Anna P. Durbin · Takoma Park, US
• Peter L. Collins · Kensington, US
• Brian R. Murphy · Bethesda, US

Key dates

• Filing date: Jul 9, 1999
• Grant date: Jun 25, 2002
• Expiry date: Jul 9, 2019

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2760/18661
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Recombinant parainfluenza virus (PIV) are provided in which expression of the C, D and/or V translational open reading frame(s) (ORFs) is reduced or ablated to yield novel PIV vaccine candidates. Expression of the C, D and/or V ORF(s) is reduced or ablated by modifying a recombinant PIV genome or antigenome, for example by introduction of a stop codon, by a mutation in an RNA editing site, by a mutation that alters the amino acid specified by an initiation codon, or by a frame shift mutation in the targeted ORF(s). Alternatively, the C, D and/or V ORF(s) is deleted in whole or in part to render the protein(s) encoded thereby partially or entirely non-functional or to disrupt protein expression altogether. C, D and/or V ORF(s) deletion and knock out mutants possess highly desirable phenotypic characteristics for vaccine development. These deletion and knock out mutations changes specify one or more desired phenotypic changes in the resulting virus or subviral particle. Vaccine candidates are generated that show a change in viral growth characteristics, attenuation, plaque size, and/or a change in cytopathogenicity, among other novel phenotypes. A variety of additional mutations and …