Intranasal immunization with a helper-dependent adenoviral vector expressing the codon-optimized fusion glycoprotein of human respiratory syncytial virus elicits protective immunity in BALB/c mice

Virol J. 2013 Jun 7:10:183. doi: 10.1186/1743-422X-10-183.

Abstract

Background: Human respiratory syncytial virus (RSV) is a serious pediatric pathogen of the lower respiratory tract. Currently, there is no clinically approved vaccine against RSV infection. Recent studies have shown that helper-dependent adenoviral (HDAd) vectors may represent effective and safe vaccine vectors. However, viral challenge has not been investigated following mucosal vaccination with HDAd vector vaccines.

Methods: To explore the role played by HDAd as an intranasally administered RSV vaccine vector, we constructed a HDAd vector encoding the codon optimized fusion glycoprotein (Fsyn) of RSV, designated HDAd-Fsyn, and delivered intranasally HDAd-Fsyn to mice.

Results: RSV-specific humoral and cellular immune responses were generated in BALB/c mice, and serum IgG with neutralizing activity was significantly elevated after a homologous boost with intranasal (i.n.) application of HDAd-Fsyn. Humoral immune responses could be measured even 14 weeks after a single immunization. Immunization with i.n. HDAd-Fsyn led to effective protection against RSV infection on challenge.

Conclusion: The results indicate that HDAd-Fsyn can induce powerful systemic immunity against subsequent i.n. RSV challenge in a mouse model and is a promising candidate vaccine against RSV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Administration, Intranasal
  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Disease Models, Animal
  • Drug Carriers
  • Female
  • Genetic Vectors
  • Immunoglobulin G / blood
  • Lung / virology
  • Mice
  • Mice, Inbred BALB C
  • Respiratory Syncytial Virus Infections / immunology
  • 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 / genetics
  • Respiratory Syncytial Virus, Human / immunology*
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Viral Fusion Proteins / genetics
  • Viral Fusion Proteins / immunology*
  • Viral Load

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Drug Carriers
  • F protein, human respiratory syncytial virus
  • Immunoglobulin G
  • Respiratory Syncytial Virus Vaccines
  • Vaccines, Synthetic
  • Viral Fusion Proteins