Sendai virus recombinant vaccine expressing a secreted, unconstrained respiratory syncytial virus fusion protein protects against RSV in cotton rats

Int Immunol. 2015 May;27(5):229-36. doi: 10.1093/intimm/dxu107. Epub 2014 Dec 4.

Abstract

The respiratory syncytial virus (RSV) is responsible for as many as 199000 annual deaths worldwide. Currently, there is no standard treatment for RSV disease and no vaccine. Sendai virus (SeV) is an attractive pediatric vaccine candidate because it elicits robust and long-lasting virus-specific B cell and T cell activities in systemic and mucosal tissues. The virus serves as a gene delivery system as well as a Jennerian vaccine against its close cousin, human parainfluenza virus type 1. Here we describe the testing of a recombinant SeV (SeVRSV-Fs) that expresses an unconstrained, secreted RSV-F protein as a vaccine against RSV in cotton rats. After a single intranasal immunization of cotton rats with SeVRSV-Fs, RSV-specific binding and neutralizing antibodies were generated. These antibodies exhibited cross-reactivity with both RSV A and B isolates. RSV-F-specific IFN-γ-producing T cells were also activated. The SeVRSV-Fs vaccine conferred protection against RSV challenge without enhanced immunopathology. In total, results showed that an SeV recombinant that expresses RSV F in an unconstrained, soluble form can induce humoral and cellular immunity that protects against infection with RSV.

Keywords: Sendai virus; protection; respiratory syncytial virus; secreted fusion protein; unconstrained F; vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antibodies, Viral / metabolism
  • Disease Models, Animal
  • Gene Transfer Techniques
  • Humans
  • Immunization
  • Interferon-gamma / metabolism
  • Lymphocyte Activation
  • Rats
  • Recombinant Fusion Proteins / genetics
  • Respiratory Syncytial Virus Infections / immunology
  • Respiratory Syncytial Virus Infections / prevention & control*
  • Respiratory Syncytial Viruses / genetics
  • Respiratory Syncytial Viruses / metabolism*
  • Sendai virus / genetics
  • Sendai virus / immunology*
  • Sigmodontinae
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / virology
  • Viral Fusion Proteins / genetics
  • Viral Vaccines / administration & dosage*
  • Viral Vaccines / genetics

Substances

  • Antibodies, Viral
  • Recombinant Fusion Proteins
  • Viral Fusion Proteins
  • Viral Vaccines
  • Interferon-gamma