Recombinant Rabies Viruses Expressing GM-CSF or Flagellin Are Effective Vaccines for Both Intramuscular and Oral Immunizations
Open Access
- 20 May 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (5), e63384
- https://doi.org/10.1371/journal.pone.0063384
Abstract
Our previous studies indicated that recombinant rabies viruses (rRABV) expressing chemokines or cytokines (including GM-CSF) could enhance the immunogenicity by recruiting and/or activating dendritic cells (DC). In this study, bacterial flagellin was cloned into the RABV genome and recombinant virus LBNSE-Flagellin was rescued. To compare the immunogenicity of LBNSE-Flagellin with recombinant virus expressing GMCSF (LBNSE-GMCSF), mice were immunized with each of these rRABVs by intramuscular (i.m.) or oral route. The parent virus (LBNSE) without expression of any foreign molecules was included for comparison. The i.m.-immunized mice were bled at three weeks after the immunization for the measurement of virus neutralizing antibody (VNA) and then challenged with 50 LD50 challenge virus standard (CVS-24). Orally immunized mice were boosted after three weeks and then bled and challenged one week after the booster immunization. It was found that both LBNSE-GMCSF and LBNSE-Flagellin recruited/activated more DCs and B cells in the periphery, stimulated higher levels of adaptive immune responses (VNA), and protected more mice against challenge infection than the parent virus LBNSE in both the i.m. and the orally immunized groups. Together, these studies suggest that recombinant RABV expressing GM-CSF or flagellin are more immunogenic than the parent virus in both i.m. and oral immunizations.Keywords
This publication has 69 references indexed in Scilit:
- Eliminating Rabies in EstoniaPLoS Neglected Tropical Diseases, 2012
- Rabies Virus Expressing Dendritic Cell-Activating Molecules Enhances the Innate and Adaptive Immune Response to VaccinationJournal of Virology, 2011
- Stimulation of Human Dendritic Cells by Wild-Type and M Protein Mutant Vesicular Stomatitis Viruses Engineered To Express Bacterial FlagellinJournal of Virology, 2010
- Expression of MIP-1α (CCL3) by a Recombinant Rabies Virus Enhances Its Immunogenicity by Inducing Innate Immunity and Recruiting Dendritic Cells and B CellsJournal of Virology, 2010
- A Recombinant Flagellin-Poxvirus Fusion Protein Vaccine Elicits Complement-Dependent Protection Against Respiratory Challenge with Vaccinia Virus in MiceViral Immunology, 2010
- Flagellin-F1-V Fusion Protein Is an Effective Plague Vaccine in Mice and Two Species of Nonhuman PrimatesClinical and Vaccine Immunology, 2009
- Mucosal adjuvant activity of flagellin in aged miceMechanisms of Ageing and Development, 2008
- Dominance of a Nonpathogenic Glycoprotein Gene over a Pathogenic Glycoprotein Gene in Rabies VirusJournal of Virology, 2007
- DC-based cancer vaccinesJCI Insight, 2007
- Comparative pathogenesis of the SAD-L16 strain of rabies virus and a mutant modifying the dynein light chain binding site of the rabies virus phosphoprotein in young miceVirus Research, 2005