摘要:
Isolated polynucleotide molecules provide RSV genome and antigenomes, including that of human, bovine or murine RSV or RSV-like viruses, and chimera thereof. The recombinant genome or antigenome can be expressed with a nucleocapsid (N) protein, a nucleocapsid phosphoprotein (P), a large (L) polymerase protein, and an RNA polymerase elongation factor to produce isolated infectious RSV particles. The recombinant RSV genome and antigenome can be modified to produce desired phenotypic changes, such as attenuated viruses for vaccine use.
摘要:
RNA synthesis by the paramyxovirus respiratory syncytial virus (RSV), a ubiquitous human pathogen, was found to be more complex than previously appreciated for the nonsegmented negative-strand RNA viruses. Intracellular RNA replication of a plasmid-encoded “minigenome” analog of viral genomic RNA was directed by coexpression of the nucleocapsid (N) protein, nucleocapsid phosphoprotein (P), and the large polymerase (L) protein. But, under these conditions, it appeared that the greater part of mRNA synthesis terminated prematurely. However, coexpression of the M2 (ORF1) gene resulted in the efficient production of full-length mRNA. Thus, these results demonstrate that expression of the upstream ORF1, which encoded the previously described 22-kDa M2 protein, was associated with transcription elongation. Accordingly, the claimed invention is directed toward infectious recombinant RSV particles which comprise a recombinant genome or antigenome, as well as the RSV proteins N, P, L, and the RNA polymerase elongation factor M2. This system will permit the introduction of defined changes into infectious RSV which will prove useful in a variety of applications, such as the analysis of RSV molecular biology and pathogenesis, the development of attenuated RSV immunogenic compositions for the preparation of RSV-specific immunological reagents, and the expression of foreign antigens.
摘要:
An altered G protein or portion thereof of RSV which retains immunogenicity and which, when incorporated into an immunogenic composition or vaccine and administered to a vertebrate, does not induce enhanced disease (e.g., atypical pulmonary inflammation such as pulmonary eosinophilia) upon subsequent infection with RSV, is disclosed. In a particular embodiment, the altered G protein comprises an alteration in one or more regions selected from the group consisting of the region from amino acid 159 to amino acid 198, the region from amino acid 159 to amino acid 174, the region from amino acid 171 to amino acid 187, the region from amino acid 176 to amino acid 190, and the region from amino acid 184 to amino acid 198 of the RSV G protein. Immunogenic compositions and vaccines comprising the altered RSV G protein, and optionally comprising RSV F protein, are also disclosed.
摘要:
A polypeptide useful as an immunogen element and characterized in that it is carried on the peptide sequence between amino acid residues 130-230 of the G protein sequence of the human respiratory syncytial virus of sub-groups A and B, or of the bovine respiratory syncytial virus, or on a sequence at least 80% homologous thereto. An immunogenic agent or pharmaceutical composition containing said polypeptide, and methods for preparing and using the same, are also disclosed.
摘要:
A polypeptide useful as an immunogen element and characterized in that it is carried on the peptide sequence between amino acid residues 130-230 of the G protein sequence of the human respiratory syncytial virus of sub-groups A and B, or of the bovine respiratory syncytial virus, or on a sequence at least 80% homologous thereto. An immunogenic agent or pharmaceutical composition containing said polypeptide, and methods for preparing and using the same, are also disclosed.
摘要:
The present invention relates to peptides which exhibit potent anti-retroviral activity. The peptides of the invention are derived from regions of viral fusion proteins referred to as HR1 and HR2. In particular, the invention relates to peptides referred to herein as DP107 and DP178 which comprise amino acid sequences corresponding to sequences found in the HR1 and HR2 regions, respectively of the HIV-1LAI gp41 protein. The invention further relates to “DP107-like” and “DP178-like” peptides that are derived from HR1 and HR2 regions, respectively, of other proteins, including DP107-like and DP178-like peptides derived from the HR1 and HR2 regions of the F1 subunit of the respiratory syncytial virus fusion protein.
摘要:
The nucleic acid and the corresponding amino acid sequence for the attachment glycoprotein of Avian Metapneumovirus (Colorado) Type C strain is provided. The nucleotide sequence is 1,321 base pairs with only one substantial open reading frame encoding a glycoprotein of about 435 amino acids with a predicted Mr of about 48,483 and a net charge of about 23.15 at neutral pH.
摘要:
Immunogenic envelope glycoproteins are produced from enveloped virus, such as of the paramyxoviridae family, particularly PIV-3 and RSV, by culturing the virus in the substantial absence of exogenous serum proteins, isolating the virus from the tissue culture, solubilizing the envelope glycoproteins and isolating the solubilized envelope glycoproteins by chromatography.
摘要:
The present invention relates to recombinant bovine parainfluenza virus (bPIV) cDNA or RNA which may be used to express heterologous gene products in appropriate host cell systems and/or to rescue negative strand RNA recombinant viruses that express, package, and/or present the heterologous gene product. The chimeric viruses and expression products may advantageously be used in vaccine formulations including vaccines against a broad range of pathogens and antigens.
摘要:
The present invention relates to recombinant DNA molecules which encode bovine respiratory syncytial (BRS) virus proteins, to BRS virus proteins, and peptides and to recombinant BRS virus vaccines produced therefrom. It is based, in part, on the cloning of substantially full length cDNAs which encode the entire BRS virus G, F, and N proteins. According to particular embodiments of the invention, DNA encoding a BRS virus protein or peptide may be used to diagnose BRS virus infection, or, alternatively, may be inserted into an expression vector, including, but not limited to, vaccinia virus as well as bacterial, yeast, insect, or other vertebrate vectors. These expression vectors may be utilized to produce the BRS virus protein or peptide in quantity; the resulting substantially pure viral peptide or protein may be incorporated into subunit vaccine formulations or may be used to generate monoclonal or polyclonal antibodies which may be utilized in diagnosis of BRS virus infection or passive immunization. In additional embodiments, BRS virus protein sequence provided by the invention may be used to produce synthetic peptides or proteins which may be utilized in subunit vaccines, or polyclonal or monoclonal antibody production. Alternatively, a nonpathogenic expression vector containing the genes, parts of the genes, any combination of the genes, or parts thereof may itself be utilized as a recombinant virus vaccine.