Parainfluenza virus type 3 expressing the native or soluble fusion (F) Protein of Respiratory Syncytial Virus (RSV) confers protection from RSV infection in African green monkeys

J Virol. 2004 Oct;78(20):11198-207. doi: 10.1128/JVI.78.20.11198-11207.2004.

Abstract

Respiratory syncytial virus (RSV) causes respiratory disease in young children, the elderly, and immunocompromised individuals, often resulting in hospitalization and/or death. After more than 40 years of research, a Food and Drug Administration-approved vaccine for RSV is still not available. In this study, a chimeric bovine/human (b/h) parainfluenza virus type 3 (PIV3) expressing the human PIV3 (hPIV3) fusion (F) and hemagglutinin-neuraminidase (HN) proteins from an otherwise bovine PIV3 (bPIV3) genome was employed as a vector for RSV antigen expression with the aim of generating novel RSV vaccines. b/h PIV3 vaccine candidates expressing native or soluble RSV F proteins were evaluated for efficacy and immunogenicity in a nonhuman primate model. b/h PIV3 is suited for development of pediatric vaccines since bPIV3 had already been evaluated in clinical studies in 1- and 2-month-old infants and was found to be safe, immunogenic, and nontransmissible in a day care setting (Karron et al., Pediatr. Infect. Dis. J. 15:650-654, 1996; Lee et al., J. Infect. Dis. 184:909-913, 2001). African green monkeys immunized with b/h PIV3 expressing either the native or soluble RSV F protein were protected from challenge with wild-type RSV and produced RSV neutralizing and RSV F-protein specific immunoglobulin G serum antibodies. The PIV3-vectored RSV vaccines evaluated here further underscore the utility of this vector system for developing safe and immunogenic pediatric respiratory virus vaccines.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Viral / blood*
  • Chlorocebus aethiops
  • Genetic Vectors*
  • Humans
  • Parainfluenza Virus 3, Human / genetics
  • Parainfluenza Virus 3, Human / metabolism*
  • Parainfluenza Virus 3, Human / physiology
  • Respiratory Syncytial Virus Infections / prevention & control*
  • Respiratory Syncytial Virus Vaccines / administration & dosage
  • Respiratory Syncytial Virus Vaccines / genetics
  • Respiratory Syncytial Virus Vaccines / immunology*
  • Respiratory Syncytial Virus, Human / immunology
  • Respiratory Syncytial Virus, Human / pathogenicity
  • Respiratory System / virology
  • Solubility
  • Vaccination
  • Vero Cells
  • Viral Proteins / genetics
  • Viral Proteins / immunology*
  • Viral Proteins / metabolism
  • Virus Replication

Substances

  • Antibodies, Viral
  • Respiratory Syncytial Virus Vaccines
  • Viral Proteins