摘要:
Recombinant human parainfluenza virus type 2 (HPIV2) viruses and related immunogenic compositions and methods are provided. The recombinant HPIV2 viruses, including HPIV2 chimeric and chimeric vector viruses, provided according to the invention are infectious and attenuated in permissive mammalian subjects, including humans, and are useful in immunogenic compositions for eliciting an immune responses against one or more PIVs, against one or more non-PIV pathogens, or against a PIV and a non-PIV pathogen. Also provided are isolated polynucleotide molecules and vectors incorporating a recombinant HPIV2 genome or antigenome.
摘要:
Recombinant human parainfluenza virus type 2 (HPIV2) viruses and related immunogenic compositions and methods are provided. The recombinant HPIV2 viruses, including HPIV2 chimeric and chimeric vector viruses, provided according to the invention are infectious and attenuated in permissive mammalian subjects, including humans, and are useful in immunogenic compositions for eliciting an immune responses against one or more PIVs, against one or more non-PIV pathogens, or against a PIV and a non-PIV pathogen. Also provided are isolated polynucleotide molecules and vectors incorporating a recombinant HPIV2 genome or antigenome.
摘要:
Recombinant human parainfluenza virus type 1 (HPIV1) compostions, formulations and methods are provided. The recombinant HPIV1 viruses and HPIV1 chimeric and chimeric vector viruses provided according to the invention are infectious and attenuated in permissive mammalian subjects, including humans, and are useful in immunogenic composition s for eliciting an immune responses against one or more PIVs, against one or more non-PIV pathogens, or against a PIV and a non-PIV pathogen. Also provided are isolated polynucleotide molecules and vectors incorporating a recombinant HPIV1 genome or antigenome.
摘要:
Recombinant human parainfluenza virus type 2 (HPIV2) viruses and related immunogenic compositions and methods are provided. The recombinant HPIV2 viruses, including HPIV2 chimeric and chimeric vector viruses, provided according to the invention are infectious and attenuated in permissive mammalian subjects, including humans, and are useful in immunogenic compositions for eliciting an immune responses against one or more PIVs, against one or more non-PIV pathogens, or against a PIV and a non-PIV pathogen. Also provided are isolated polynucleotide molecules and vectors incorporating a recombinant HPIV2 genome or antigenome.
摘要:
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 and 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 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.
摘要:
Attenuated, recombinant negative stranded RNA viruses suitable for vaccine use are produced from one or more isolated polynucleotide molecules encoding the virus. A recombinant genome or antigenome of the subject virus is modified to encode a mutation within a recombinant protein of the virus at one or more amino acid positions(s) corresponding to a site of an attenuating mutation in a heretologous, mutant negative stranded RNA virus. A similar attenuating mutation as identified in the heterologous negative stranded RNA virus is thus incorporated at a corresponding site within the recombinant virus to confer an attenuated phenotype on the recombinant virus. The attenuating mutation incorporated in the recombinant virus may be identical or conservative in relation to the attenuating mutation identified in the heterologous, mutant virus. By the transfer of mutations into recombinant negative stranded RNA viruses in this matter, candidate vaccine viruses are engineered to elicit a desired immune response against a subject virus in a host susceptible to infection thereby.
摘要:
The invention provides isolated nucleic acids encoding recombinant genomes or antigenomes of Human Parainfluenza Viruses that are useful as vaccines. The recombinant genomes or antigenomes can be incorporated into expression vectors for production of recombinant viruses in vitro. The invention also provides recombinant Human Parainfluenza viruses having one or more mutations that attenuate replication of the virus in a host.
摘要:
The invention provides self replicating infectious recombinant paramyxoviruses where the P and C genes are separated rated. The recombinant paramyxoviruses preferably have one or more attenuating mutations and/or at least one temperature sensitive mutation and one non-temperature sensitive mutation. In some embodiments, the recombinant paramyxovirus has a separate variant polynucleotide encoding a C protein and a separate monocistronic polynucleotide encoding a P protein. Also provided are compositions and methods for using the recombinant paramyxoviruses as described herein.
摘要:
Chimeric parainfluenza viruses (PIVs) are provided that incorporate a PIV vector genome or antigenome modified to encode a chimeric glycoprotein incorporating one or more heterologous antigenic domains, fragments, or epitopes of a second, antigenically distinct HPIV. 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, and, optionally against respiratory syncytial virus (RSV). Also provided are isolated polynucleotide molecules and vectors incorporating a chimeric PIV genome or antigenome which includes a HPIV vector genome or antigenome combined or integrated with one or more heterologous genome segment(s) encoding one or more antigenic determinant(s) of a heterologous PIV to encode a chimeric glycoprotein. In preferred aspects of the invention, the chimeric virus is attenuated for use as a vaccine agent by additional mutations or nucleotide modifications introduced into the chimeric genome or antigenome.
摘要:
Isolated polynucleotide molecules provide recombinant PIV genomes and antigenomes for production of recombinant PIV vaccines. The recombinant genome or antigenome can be expressed with a nucleoprotein (N), phosphoprotein (P), and a large (L) polymerase protein to produce isolated infectious PIV particles. The recombinant PIV genome and antigenome can be modified to produce desired changes, for example to incorporate attenuating mutations from biologically derived PIV mutants or to create chimeric PIV clones, to generate attenuated, immunogenic viruses for vaccine use.