Complementing defective viruses that express separate paramyxovirus glycoproteins provide a new vaccine vector approach

J Virol. 2011 Mar;85(5):2004-11. doi: 10.1128/JVI.01852-10. Epub 2010 Dec 22.

Abstract

Replication-defective vaccine vectors based on vesicular stomatitis virus (VSV) lacking its envelope glycoprotein gene (G) are highly effective in animal models. However, such ΔG vectors are difficult to grow because they require complementation with the VSV G protein. In addition, the complementing G protein induces neutralizing antibodies in animals and thus limits multiple vector applications. In the process of generating an experimental Nipah virus (a paramyxovirus) vaccine, we generated two defective VSVΔG vectors, each expressing one of the two Nipah virus (NiV) glycoproteins (G and F) that are both required for virus entry to host cells. These replication-defective VSV vectors were effective at generating NiV neutralizing antibody in mice. Most interestingly, we found that these two defective viruses could be grown together and passaged in tissue culture cells in the absence of VSV G complementation. This mixture of complementing defective viruses was also highly effective at generating NiV neutralizing antibody in animals. This novel approach to growing and producing a vaccine from two defective viruses could be generally applicable to vaccine production for other paramyxoviruses or for other viruses where the expression of at least two different proteins is required for viral entry. Such an approach minimizes biosafety concerns that could apply to single, replication-competent VSV recombinants expressing all proteins required for infection.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line
  • Defective Viruses / genetics*
  • Defective Viruses / immunology
  • Defective Viruses / physiology
  • Female
  • Gene Expression*
  • Genetic Complementation Test
  • Genetic Vectors / genetics*
  • Genetic Vectors / immunology
  • Henipavirus Infections / immunology
  • Henipavirus Infections / prevention & control
  • Henipavirus Infections / virology
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Nipah Virus / genetics
  • Nipah Virus / immunology*
  • Vesiculovirus / genetics
  • Vesiculovirus / immunology*
  • Vesiculovirus / physiology
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology*
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology*
  • Virus Replication

Substances

  • Viral Envelope Proteins
  • Viral Vaccines