Use of recombinant parainfluenza viruses (PIVs) as vectors to protect against infection and disease caused by PIV and other human pathogens

A parainfluenza, virus technology, applied in the direction of virus antigen components, virus/phage, introduction of foreign genetic material using vectors, etc.

Inactive Publication Date: 2012-11-07
UNITED STATES OF AMERICA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The challenge that remains in this specification is that additional tools are needed to produce appropriately attenuated, immunogenic, genetically stable vaccine candidates against one or more pathogens for use in different clinical situations

Method used

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  • Use of recombinant parainfluenza viruses (PIVs) as vectors to protect against infection and disease caused by PIV and other human pathogens
  • Use of recombinant parainfluenza viruses (PIVs) as vectors to protect against infection and disease caused by PIV and other human pathogens
  • Use of recombinant parainfluenza viruses (PIVs) as vectors to protect against infection and disease caused by PIV and other human pathogens

Examples

Experimental program
Comparison scheme
Effect test

Embodiment I

[0220] Construction of cDNA encoding a chimeric PIV3 / measles virus-HA antigenome and acquisition of infectious virus

[0221] A full-length cDNA clone, p3 / 7(131)2G, has been described previously + , which encodes the complete 15462 nucleotide antigenome of the JS PIV3wt virus, and pFLCcp45L, which encodes the antigenome of a JS wt derivative containing three cp45-specific temperature-sensitive mutations in the L ORF of PIV3 (Durbin et al., Virology 235 : 323-332, 1997a; Skiadopoulos et al., J. Virol. 72: 1762-8, 1998, incorporated herein by reference). These clones were used as vectors for insertion of the HA gene of measles virus to generate wild-type and attenuated HPIV3 chimeric constructs expressing heterologous epitopes such as the HA protein of measles virus. The size of each insert containing the measles HA gene is a multiple of 6, allowing chimeric viruses derived from cDNA to conform to the 6 rule (Durbin et al., Virology 234:74-83, 1997b, incorporated herein by refe...

Embodiment II

[0240] Chimeric rPIV3 containing measles virus epitopes replicates efficiently in hamsters and induces high titers of anti-HPIV3 and anti-measles antibodies

[0241] Determination of Replication and Immunogenicity of rPIV3(HA) Virus in Hamsters

[0242] The level of replication of chimeric rPIV3 containing measles virus epitopes was compared to that of its parental rPIV3 to determine whether the acquisition of determinants such as HA inserts significantly altered its ability to replicate and induce an immune response in vivo. In two different experiments, 0.1 ml of 10 6.0 EMEM (Life Tchnologies) of rJS, rcp45L, rcp45L(HAP-M), rcp45L(HA N-P), rPIV3(HA HN-L) or rPIV3(HA P-M) of PFU (Table 2 and Table 3). On day 4 after inoculation, the hamsters were sacrificed, and the lungs and turbinates were removed. Turbinates and lungs were homogenized in 10% and 20% w / v L-15 (Quality Biologicals, Gaithersburg, MD) suspensions, respectively, and samples snap frozen. Viruses present in th...

Embodiment III

[0271] Construction of an antigenomic cDNA encoding a chimeric HPIV3-1 vector containing the HPIV2 HN gene as an external transcription / translation unit inserted between the F and HN genes, and acquisition of infectious virus

[0272] rPIV3-1 is a recombinant chimeric HPIV3 in which the HN and F genes are replaced with those of HPIV1 (see, e.g., Skiadopoulos et al., Vaccine 18:503-510, 1999; Tao et al., Vaccine 17: 1100-1108, 1999; U.S. Patent Application Serial No. 09 / 083,793, filed May 22, 1998; U.S. Patent Application Serial No. 09 / 458,813, filed December 10, 1999; U.S. Patent Application Serial No., filed December 10, 1999 No. 09 / 459,062, both of which are incorporated herein by reference). In this example, the HN gene of HPIV2 was inserted into the rPIV3-1 chimeric virus, which was used as a vector for generating chimeric derivative viruses, containing introduced heterologous antigenic determinants from HPIV2, capable of producing protection against HPIV1 and HPIV2. The ...

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Abstract

Chimeric parainfluenza viruses (PIVs) are provided that incorporate a PIV vector genome or antigenome and one or more antigenic determinant(s) of a heterologous PIV or non-PIV pathogen. These chimeric viruses are infectious and attenuated in humans and other mammals and are useful in vaccine formulations for eliciting an immune responses against one or more PIVs, or against a PIV and non-PIV pathogen. Also provided are isolated polynucleotide molecules and vectors incorporating a chimeric PIV genome or antigenome which includes a partial or complete PIV vector genome or antigenome combined or integrated with one or more heterologous gene(s) or genome segment(s) encoding antigenic determinant(s) of a heterologous PIV or non-PIV pathogen. In preferred aspects of the invention, chimeric PIV incorporate a partial or complete human, bovine, or human-bovine chimeric, PIV vector genome or antigenome combined with one or more heterologous gene(s) or genome segment(s) from a heterologous PIV or non-PIV pathogen, wherein the chimeric virus is attenuated for use as a vaccine agent by any of a variety of mutations and nucleotide modifications introduced into the chimeric genome or antigenome.

Description

[0001] The application date is December 8, 2000, the application number is 00805939.X, and the title of the invention is "Use of recombinant parainfluenza virus (PIV) as a carrier to provide protection against infections and diseases caused by PIV and other human pathogens" A divisional application of an invention patent application. Background of the invention [0002] Human parainfluenza virus type 3 (HPIV3) is a common cause of severe lower respiratory tract infection in infants and children under one year of age. Second only to respiratory syncytial virus (RSV) as the leading cause of hospitalization for viral lower respiratory disease in this age group (Collins et al., pp. 1205-1243 in B.N. Fields (Knipe et al.), Fields Virology", Third Edition, Vol. 1, Lippincott-Raven Publishers, Philadelphia, 1996; Crowe et al., Vaccine 13:415-421, 1995; Marx et al., J.Infect.Dis .) 176:1423-1427, 1997). Infection with the virus results in higher morbidity in children under 3 years o...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N7/01C12N15/45C07K14/115C07K19/00A61K39/295C12N15/62C12N15/63A61K39/00C12N15/09A61K39/12A61K39/145A61K39/205A61K39/245A61K48/00A61P37/02C12N7/00C12N15/86C12R1/93
CPCA61K2039/5256C12N2760/18622C12N2760/18643A61K39/00C12N15/86C07K14/005A61P37/02
Inventor B·R·摩菲P·L·克林斯A·C·施密特A·P·德宾M·H·斯奇雅多普罗斯陶涛
Owner UNITED STATES OF AMERICA
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