title: Recombinant rabies viruses expressing GM-CSF or flagellin are effective vaccines for both intramuscular and oral immunizations.
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.
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Animal Medicine, Huazhong Agricultural University, Wuhan, Hubei, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zhang
authors.forename: Guiping
authors.initials: G
authors.lastname: Ren
authors.forename: Clement W
authors.initials: CW
authors.lastname: Gnanadurai
authors.forename: Zhenguang
authors.initials: Z
authors.lastname: Li
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Chai
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Christina M
authors.initials: CM
authors.lastname: Leyson
authors.forename: Wenxue
authors.initials: W
authors.lastname: Wu
authors.forename: Min
authors.initials: M
authors.lastname: Cui
authors.forename: Zhen F
authors.initials: ZF
authors.lastname: Fu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D002460:Cell Line; D006224:Cricetinae; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005408:Flagellin / Q000096:biosynthesis*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D006801:Humans; D007273:Injections, Intramuscular; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D011818:Rabies / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D011820:Rabies virus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage; D014765:Viral Vaccines / Q000008:administration & dosage*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D005408:Flagellin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor