An inactivated recombinant rabies CVS-11 virus expressing two copies of the glycoprotein elicits a higher level of neutralizing antibodies and provides better protection in mice

Virus Genes. 2014 Jun;48(3):411-20. doi: 10.1007/s11262-014-1049-9. Epub 2014 Feb 18.

Abstract

The rabies virus (RABV) G protein is the primary contributor to the pathogenicity and protective immunity of RABV. In this study, we generated a recombinant rCVS-11-G strain containing two copies of the G protein derived from the pathogenic wild-type (wt) CVS-11 strain and based on its infectious clone. Compared with the wtCVS-11 strain, the rCVS-11-G strain possessed a larger virion and 1.4-fold more G protein, but it exhibited a similar growth property to the rCVS-11 strain, including passaging stability in vitro. qPCR results showed that the two G genes were over-expressed in BHK-21 cells infected with the rCVS-11-G strain. However, the rCVS-11-G strain presented an 80 % lower LD50 than the wtCVS-11 strain when intracranially (i.c.) inoculated in adult mice. Adult mice that were either intracranially (i.c.) or intramuscularly (i.m.) inoculated with rCVS-11-G strain developed more acute neurological symptoms and greater mortality than those inoculated with the wtCVS-11 strain. Furthermore, the rCVS-11-G strain was more easily and rapidly taken up by neuroblastoma cells. These data indicated that the rCVS-11-G strain might have increased neurotropism because of the over-expression of the pathogenic G protein. The inactivated rCVS-11-G strain induced significantly higher levels of virus neutralization antibodies and provided better protection from street rabies virus challenge in mice. Therefore, the rCVS-11-G strain may be a promising inactivated vaccine strain due to its better immunogenicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / immunology
  • Female
  • Glycoproteins / administration & dosage
  • Glycoproteins / immunology
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Rabies / immunology*
  • Rabies / prevention & control*
  • Rabies / virology
  • Rabies Vaccines / administration & dosage
  • Rabies Vaccines / genetics
  • Rabies Vaccines / immunology*
  • Rabies virus / genetics
  • Rabies virus / immunology*
  • Vaccines, Inactivated / administration & dosage
  • Vaccines, Inactivated / genetics
  • Vaccines, Inactivated / immunology
  • Viral Envelope Proteins / administration & dosage
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Glycoproteins
  • Rabies Vaccines
  • Vaccines, Inactivated
  • Viral Envelope Proteins