title: Intracerebral administration of recombinant rabies virus expressing GM-CSF prevents the development of rabies after infection with street virus.
abstract: Recently it was found that prior immunization with recombinant rabies virus (RABV) expressing granulocyte-macrophage colony-stimulating factor (GM-CSF) (LBNSE-GM-CSF) resulted in high innate/adaptive immune responses and protection against challenge with virulent RABV (Wen et al., JVI, 2011). In this study, the ability of LBNSE-GM-CSF to prevent animals from developing rabies was investigated in mice after infection with lethal doses of street RABV. It was found that intracerebral administration of LBNSE-GM-CSF protected more mice from developing rabies than sham-treated mice as late as day 5 after infection with street RABV. Intracerebral administration of LBNSE-GM-CSF resulted in significantly higher levels of chemokine/cytokine expression and more infiltration of inflammatory and immune cells into the central nervous system (CNS) than sham-administration or administration with UV-inactivated LBNSE-GM-CSF. Enhancement of blood-brain barrier (BBB) permeability and increases in virus neutralizing antibodies (VNA) were also observed in mice treated with LBNSE-GM-CSF. On the other hand, intracerebral administration with UV-inactivated LBNSE-GM-CSF did not increase protection despite the fact that VNA were induced in the periphery. However, intracerebral administration with chemoattractant protein-1 (MCP-1, also termed CCL2) increased significantly the protective efficacy of UV-inactivated LBNSE-GM-CSF. Together these studies confirm that direct administration of LBNSE-GM-CSF can enhance the innate and adaptive immunity as well as the BBB permeability, thus allowing infiltration of inflammatory cells and other immune effectors enter into the CNS to clear the virus and prevent the development of rabies.
authors: Department of Pathology, University of Georgia, Athens, Georgia, United States of America.
authors: Hualei
authors: H
authors: Wang
authors: Guoqing
authors: G
authors: Zhang
authors: Yongjun
authors: Y
authors: Wen
authors: Songtao
authors: S
authors: Yang
authors: Xianzhu
authors: X
authors: Xia
authors: Zhen F
authors: ZF
authors: Fu
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D000818:Animals; D057134:Antibodies, Neutralizing / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018932:Chemokine CCL2 / Q000008:administration & dosage / Q000494:pharmacology; D018925:Chemokines / Q000378:metabolism; D004274:DNA, Recombinant / Q000235:genetics*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000235:genetics / Q000494:pharmacology*; D007113:Immunity, Innate / Q000187:drug effects; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D011818:Rabies / Q000517:prevention & control*; D011820:Rabies virus / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity*; D013997:Time Factors; D014466:Ultraviolet Rays
chemical_list: D057134:Antibodies, Neutralizing; D018932:Chemokine CCL2; D018925:Chemokines; D004274:DNA, Recombinant; D016178:Granulocyte-Macrophage Colony-Stimulating Factor