Document Detail


Mucosal immunization of rhesus monkeys against respiratory syncytial virus subgroups A and B and human parainfluenza virus type 3 by using a live cDNA-derived vaccine based on a host range-attenuated bovine parainfluenza virus type 3 vector backbone.
MedLine Citation:
PMID:  11773385     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Reverse genetics was used to develop a two-component, trivalent live attenuated vaccine against human parainfluenza virus type 3 (HPIV3) and respiratory syncytial virus (RSV) subgroups A and B. The backbone for each of the two components of this vaccine was the attenuated recombinant bovine/human PIV3 (rB/HPIV3), a recombinant BPIV3 in which the bovine HN and F protective antigens are replaced by their HPIV3 counterparts (48). This chimera retains the well-characterized host range attenuation phenotype of BPIV3, which appears to be appropriate for immunization of young infants. The open reading frames (ORFs) for the G and F major protective antigens of RSV subgroup A and B were each placed under the control of PIV3 transcription signals and inserted individually or in homologous pairs as supernumerary genes in the promoter proximal position of rB/HPIV3. The level of replication of rB/HPIV3-RSV chimeric viruses in the respiratory tract of rhesus monkeys was similar to that of their parent virus rB/HPIV3, and each of the chimeras induced a robust immune response to both RSV and HPIV3. RSV-neutralizing antibody titers induced by rB/HPIV3-RSV chimeric viruses were equivalent to those induced by infection with wild-type RSV, and HPIV3-specific antibody responses were similar to, or slightly less than, after infection with the rB/HPIV3 vector itself. This study describes a novel vaccine strategy against RSV in which vaccine viruses with a common attenuated backbone, specifically rB/HPIV3 derivatives expressing the G and/or F major protective antigens of RSV subgroup A and of RSV subgroup B, are used to immunize by the intranasal route against RSV and HPIV3, which are the first and second most important viral agents of pediatric respiratory tract disease worldwide.
Authors:
Alexander C Schmidt; Daniel R Wenzke; Josephine M McAuliffe; Marisa St Claire; William R Elkins; Brian R Murphy; Peter L Collins
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of virology     Volume:  76     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-01-04     Completed Date:  2002-02-12     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1089-99     Citation Subset:  IM    
Affiliation:
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. aschmidt@niaid.nih.gov
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Viral / biosynthesis,  blood,  immunology
Antigens, Viral / genetics,  immunology
Base Sequence
Cattle
Cell Line
Cercopithecus aethiops
DNA, Viral
Disease Models, Animal
Genetic Vectors* / genetics,  physiology
Genome, Viral
HN Protein / genetics,  immunology
Humans
Immunity, Mucosal / immunology
Macaca mulatta
Molecular Sequence Data
Mutagenesis, Insertional / methods
Open Reading Frames
Parainfluenza Vaccines / genetics,  immunology*
Parainfluenza Virus 3, Bovine* / genetics,  physiology
Parainfluenza Virus 3, Human / genetics,  immunology*
Respiratory Syncytial Virus Infections / immunology*,  prevention & control
Respiratory Syncytial Virus Vaccines / genetics,  immunology*
Respiratory Syncytial Viruses / genetics,  immunology*
Respirovirus Infections / immunology*,  prevention & control
Transcription, Genetic
Tumor Cells, Cultured
Vaccination
Vaccines, Attenuated / genetics,  immunology
Vaccines, DNA / genetics,  immunology*
Vero Cells
Viral Fusion Proteins / genetics,  immunology
Viral Proteins / genetics,  immunology
Virus Replication
Grant Support
ID/Acronym/Agency:
AI-000030/AI/NIAID NIH HHS; AI-000087/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Viral; 0/Antigens, Viral; 0/DNA, Viral; 0/HN Protein; 0/Parainfluenza Vaccines; 0/Respiratory Syncytial Virus Vaccines; 0/Vaccines, Attenuated; 0/Vaccines, DNA; 0/Viral Fusion Proteins; 0/Viral Proteins; 109300-94-9/F protein, parainfluenza virus 3
Comments/Corrections

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