Baculovirus-expressed virus-like particle vaccine in combination with DNA encoding the fusion protein confers protection against respiratory syncytial virus

Vaccine. 2014 Oct 7;32(44):5866-74. doi: 10.1016/j.vaccine.2014.08.045. Epub 2014 Aug 27.

Abstract

Respiratory syncytial virus (RSV) is a major viral agent causing significant morbidity and mortality in young infants and the elderly. There is no licensed vaccine against RSV and it is a high priority to develop a safe RSV vaccine. We determined the immunogenicity and protective efficacy of combined virus-like particle and DNA vaccines presenting RSV glycoproteins (Fd.VLP) in comparison with formalin inactivated RSV (FI-RSV). Immunization of mice with Fd.VLP induced higher ratios of IgG2a/IgG1 antibody responses compared to those with FI-RSV. Upon live RSV challenge, Fd.VLP and FI-RSV vaccines were similarly effective in clearing lung viral loads. However, FI-RSV immunized mice showed a substantial weight loss and high levels of T helper type 2 (Th2) cytokines as well as extensive lung histopathology and eosinophil infiltration. In contrast, Fd.VLP immunized mice did not exhibit Th2 type cytokines locally and systemically, which might contribute to preventing vaccine-associated RSV lung disease. These results indicate that virus-like particles in combination with DNA vaccines represent a potential approach for developing a safe and effective RSV vaccine.

Keywords: Protection; RSV; VLPs; Vaccines.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Antibody Formation
  • Baculoviridae
  • Cytokines / immunology
  • Immunoglobulin G / blood
  • Lung / pathology
  • Lung / virology
  • Mice, Inbred BALB C
  • Respiratory Syncytial Virus Infections / prevention & control*
  • Respiratory Syncytial Virus Vaccines / immunology*
  • Respiratory Syncytial Viruses / immunology
  • Th2 Cells / immunology
  • Vaccines, DNA / immunology
  • Vaccines, Inactivated / immunology
  • Vaccines, Virus-Like Particle / immunology
  • Viral Fusion Proteins / immunology*
  • Viral Load

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Cytokines
  • F protein, human respiratory syncytial virus
  • G glycoprotein, Respiratory syncytial virus
  • Immunoglobulin G
  • Respiratory Syncytial Virus Vaccines
  • Vaccines, DNA
  • Vaccines, Inactivated
  • Vaccines, Virus-Like Particle
  • Viral Fusion Proteins