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

J Virol. 2001 May;75(10):4594-603. doi: 10.1128/JVI.75.10.4594-4603.2001.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Viral / biosynthesis
  • Antibodies, Viral / blood
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology*
  • Base Sequence
  • Cattle
  • Cell Line
  • Cricetinae
  • DNA, Viral
  • Gene Expression
  • Genetic Vectors / genetics
  • Genetic Vectors / immunology*
  • Genetic Vectors / physiology
  • Humans
  • Immunity, Mucosal
  • Macaca mulatta
  • Molecular Sequence Data
  • Mutagenesis, Insertional
  • Open Reading Frames
  • Parainfluenza Vaccines / genetics
  • Parainfluenza Vaccines / immunology*
  • Parainfluenza Virus 3, Human / genetics
  • Parainfluenza Virus 3, Human / immunology*
  • Recombination, Genetic
  • Respiratory Syncytial Virus Infections / prevention & control*
  • Respiratory Syncytial Virus Vaccines / immunology*
  • Respiratory Syncytial Virus, Human / immunology*
  • Respiratory System / metabolism
  • Respirovirus / genetics
  • Respirovirus / immunology*
  • Respirovirus / physiology
  • Respirovirus Infections / prevention & control*
  • Tumor Cells, Cultured
  • Vaccination
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology*
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology*
  • Viral Fusion Proteins / genetics
  • Viral Fusion Proteins / immunology*
  • Viral Proteins / genetics
  • Viral Proteins / immunology*
  • Virus Replication

Substances

  • Antibodies, Viral
  • Antigens, Viral
  • DNA, Viral
  • Parainfluenza Vaccines
  • Respiratory Syncytial Virus Vaccines
  • Vaccines, Synthetic
  • Viral Envelope Proteins
  • Viral Fusion Proteins
  • Viral Proteins