Intranasal immunization with a replication-deficient adenoviral vector expressing the fusion glycoprotein of respiratory syncytial virus elicits protective immunity in BALB/c mice

Biochem Biophys Res Commun. 2009 Apr 17;381(4):528-32. doi: 10.1016/j.bbrc.2009.02.075. Epub 2009 Feb 20.

Abstract

Human respiratory syncytial virus (RSV) is a serious pediatric pathogen of the lower respiratory tract worldwide. There is currently no clinically approved vaccine against RSV infection. Recently, it has been shown that a replication-deficient first generation adenoviral vector (FGAd), which encodes modified RSV attachment glycoprotein (G), elicits long-term protective immunity against RSV infection in mice. The major problem in developing such a vaccine is that G protein lacks MHC-I-restricted epitopes. However, RSV fusion glycoprotein (F) is a major cytotoxic T-lymphocyte epitope in humans and mice, therefore, an FGAd-encoding F (FGAd-F) was constructed and evaluated for its potential as an RSV vaccine in a murine model. Intranasal (i.n.) immunization with FGAd-F generated serum IgG, bronchoalveolar lavage secretory IgA, and RSV-specific CD8+ T-cell responses in BALB/c mice, with characteristic balanced or mixed Th1/Th2 CD4+ T-cell responses. Serum IgG was significantly elevated after boosting with i.n. FGAd-F. Upon challenge, i.n. immunization with FGAd-F displayed an effective protective role against RSV infection. These results demonstrate FGAd-F is able to induce effective protective immunity and is a promising vaccine regimen against RSV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / physiology
  • Administration, Intranasal
  • Animals
  • Antibody Formation
  • CD8-Positive T-Lymphocytes / immunology
  • Cytotoxicity, Immunologic
  • Genetic Vectors / genetics
  • Humans
  • Lung / immunology
  • Lung / pathology
  • Lung / virology
  • Mice
  • Mice, Inbred BALB C
  • Respiratory Syncytial Virus Infections / pathology
  • Respiratory Syncytial Virus Infections / prevention & control*
  • Respiratory Syncytial Virus Vaccines / administration & dosage
  • Respiratory Syncytial Virus Vaccines / genetics
  • Respiratory Syncytial Virus Vaccines / immunology*
  • Respiratory Syncytial Viruses / immunology*
  • Vaccination
  • Viral Fusion Proteins / genetics
  • Viral Fusion Proteins / immunology*
  • Virus Replication / genetics

Substances

  • Respiratory Syncytial Virus Vaccines
  • Viral Fusion Proteins