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.
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.
Schmidt
Alexander C
AC
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. aschmidt@niaid.nih.gov
Wenzke
Daniel R
DR
McAuliffe
Josephine M
JM
St  Claire
Marisa
M
Elkins
William R
WR
Murphy
Brian R
BR
Collins
Peter L
PL
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D002417:Cattle; D002460:Cell Line; D002522:Chlorocebus aethiops; D004279:DNA, Viral; D004195:Disease Models, Animal; D005822:Genetic Vectors / Q000235:genetics / Q000502:physiology; D016679:Genome, Viral; D015707:HN Protein / Q000235:genetics / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional / Q000379:methods; D016366:Open Reading Frames; D022241:Parainfluenza Vaccines / Q000235:genetics / Q000276:immunology*; D029101:Parainfluenza Virus 3, Bovine / Q000235:genetics / Q000502:physiology; D010224:Parainfluenza Virus 3, Human / Q000235:genetics / Q000276:immunology*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000517:prevention & control; D022261:Respiratory Syncytial Virus Vaccines / Q000235:genetics / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology*; D010253:Respirovirus Infections / Q000276:immunology* / Q000517:prevention & control; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D014709:Vero Cells; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology; D014779:Virus Replication
D000914:Antibodies, Viral; D000956:Antigens, Viral; D004279:DNA, Viral; D015707:HN Protein; D022241:Parainfluenza Vaccines; D022261:Respiratory Syncytial Virus Vaccines; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA; D014760:Viral Fusion Proteins; D014764:Viral Proteins; C072983:F protein, parainfluenza virus 3