Recombinant bovine/human parainfluenza virus type 3 (B/HPIV3) expressing the respiratory syncytial virus (RSV) G and F proteins can be used to achieve simultaneous mucosal immunization against RSV and HPIV3.
Recombinant bovine/human parainfluenza virus type 3 (rB/HPIV3), a recombinant bovine PIV3 (rBPIV3) in which the F and HN genes were replaced with their HPIV3 counterparts, was used to express the major protective antigens of respiratory syncytial virus (RSV) in order to create a bivalent mucosal vaccine against RSV and HPIV3. The attenuation of rB/HPIV3 is provided by the host range restriction of the BPIV3 backbone in primates. RSV G and F open reading frames (ORFs) were placed under the control of PIV3 transcription signals and inserted individually into the rB/HPIV3 genome in the promoter-proximal position preceding the nucleocapsid protein gene. The recombinant PIV3 expressing the RSV G ORF (rB/HPIV3-G1) was not restricted in its replication in vitro, whereas the virus expressing the RSV F ORF (rB/HPIV3-F1) was eightfold restricted compared to its rB/HPIV3 parent. Both viruses replicated efficiently in the respiratory tract of hamsters, and each induced RSV serum antibody titers similar to those induced by RSV infection and anti-HPIV3 titers similar to those induced by HPIV3 infection. Immunization of hamsters with rB/HPIV3-G1, rB/HPIV3-F1, or a combination of both viruses resulted in a high level of resistance to challenge with RSV or HPIV3 28 days later. These results describe a vaccine strategy that obviates the technical challenges associated with a live attenuated RSV vaccine, providing, against the two leading viral agents of pediatric respiratory tract disease, a bivalent vaccine whose attenuation phenotype is based on the extensive host range sequence differences of BPIV3.
Schmidt
A C
AC
Laboratory of Infectious Disease, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. aschmidt@niaid.nih.gov
McAuliffe
J M
JM
Murphy
B R
BR
Collins
P L
PL
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000097:blood; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D002417:Cattle; D002460:Cell Line; D006224:Cricetinae; D004279:DNA, Viral; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D018928:Immunity, Mucosal; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D016366:Open Reading Frames; D022241:Parainfluenza Vaccines / Q000235:genetics / Q000276:immunology*; D010224:Parainfluenza Virus 3, Human / Q000235:genetics / Q000276:immunology*; D011995:Recombination, Genetic; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology*; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D012137:Respiratory System / Q000378:metabolism; D018108:Respirovirus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D010253:Respirovirus Infections / Q000517:prevention & control*; D014407:Tumor Cells, Cultured; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; 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; D022241:Parainfluenza Vaccines; D022261:Respiratory Syncytial Virus Vaccines; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; D014764:Viral Proteins