Expression of MIP-1alpha (CCL3) by a recombinant rabies virus enhances its immunogenicity by inducing innate immunity and recruiting dendritic cells and B cells

J Virol. 2010 Sep;84(18):9642-8. doi: 10.1128/JVI.00326-10. Epub 2010 Jun 30.

Abstract

Previously, we showed that overexpression of MIP-1alpha in mouse brain further decreased rabies virus (RABV) pathogenicity (L. Zhao, H. Toriumi, Y. Kuang, H. Chen, and Z. F. Fu, J. Virol., 83:11808-11818, 2009). In the present study, the immunogenicity of recombinant RABV expressing MIP-1alpha (rHEP-MIP1alpha) was determined. It was found that intramuscular immunization of BALB/c mice with rHEP-MIP1alpha resulted in a higher level of expression of MIP-1alpha at the site of inoculation, increased recruitment of dendritic cells (DCs) and mature B cells into the draining lymph nodes and the peripheral blood, and higher virus-neutralizing antibody titers than immunization with the parent rHEP and recombinant RABVs expressing RANTES (CCL5) or IP-10 (CXCL10). Our data thus demonstrate that expression of MIP-1alpha not only reduces viral pathogenicity but also enhances immunogenicity by recruiting DCs and B cells to the site of immunization, the lymph nodes, and the blood.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / virology
  • Chemokine CCL3 / biosynthesis
  • Chemokine CCL3 / genetics
  • Chemokine CCL3 / immunology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / virology
  • Immunity, Innate*
  • Injections, Intramuscular
  • Mice
  • Mice, Inbred BALB C
  • Rabies Vaccines / administration & dosage
  • Rabies Vaccines / genetics
  • Rabies Vaccines / immunology*
  • Rabies virus / genetics
  • Rabies virus / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Ccl3 protein, mouse
  • Chemokine CCL3
  • Rabies Vaccines