AIK-C measles vaccine expressing fusion protein of respiratory syncytial virus induces protective antibodies in cotton rats

Vaccine. 2011 Feb 4;29(7):1481-90. doi: 10.1016/j.vaccine.2010.12.028. Epub 2010 Dec 24.

Abstract

Respiratory syncytial virus (RSV) is the most common cause of respiratory infection in infants, and no vaccine is available. In this report, recombinant AIK-C measles vaccines, expressing the RSV G or F protein of subgroup A (MVAIK/RSV/G or F), were investigated as a RSV vaccine candidate. MVAIK/RSV/G or F had the original ts phenotype and expressed RSV/G or F protein. Cross-reactive neutralizing antibodies against RSV subgroups A and B were detected in cotton rats immunized intramuscularly with MVAIK/RSV/F but not MVAIK/RSV/G. In cotton rats infected with RSV, RSV was recovered and lung histopathological finding was compatible with interstitial pneumonia, demonstrating thickening of alveolar walls and infiltration of mononuclear cells. When cotton rats immunized with MVAIK/RSV/F were challenged with homologous RSV subgroup A, no infectious RSV was recovered and very mild inflammation was noted without RSV antigen expression. When they were challenged with subgroup B, protective efficacy decreased. When cotton rats immunized with MVAIK/RSV/G were challenged with RSV subgroup A, low levels of infectious virus were recovered from lung. When challenged with subgroup B, no protective effects was demonstrated, demonstrating large amounts of RSV antigen in bronchial-epithelial cells. MVAIK/RSV/F is promising candidate and protective effects should be confirmed in monkey model.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Cell Line
  • Cross Reactions
  • Humans
  • Lung / pathology
  • Lung / virology
  • Measles Vaccine / genetics
  • Measles Vaccine / immunology*
  • Neutralization Tests
  • Pneumonia, Viral / immunology
  • RNA, Viral / isolation & purification
  • Respiratory Syncytial Virus Infections / immunology
  • Respiratory Syncytial Virus Infections / prevention & control*
  • Respiratory Syncytial Virus Vaccines / genetics
  • Respiratory Syncytial Virus Vaccines / immunology*
  • Respiratory Syncytial Viruses / genetics
  • Respiratory Syncytial Viruses / immunology
  • Sigmodontinae
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Viral Fusion Proteins / genetics
  • Viral Fusion Proteins / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • F protein, human respiratory syncytial virus
  • G glycoprotein, Respiratory syncytial virus
  • Measles Vaccine
  • RNA, Viral
  • Respiratory Syncytial Virus Vaccines
  • Vaccines, Synthetic
  • Viral Fusion Proteins