title: Enhancement of blood-brain barrier permeability is required for intravenously administered virus neutralizing antibodies to clear an established rabies virus infection from the brain and prevent the development of rabies in mice.
abstract: Rabies virus (RABV) is a neurotropic virus that causes fatal disease in humans and animals. Currently there is no cure for rabies once clinical signs appear. It is believed that once RABV enters the central nervous system (CNS), virus neutralizing antibodies (VNAs) in the periphery cannot pass through the blood-brain barrier (BBB) and into the CNS. Furthermore, it has been hypothesized that VNAs produced in the CNS by invading B cells, rather than those produced in the periphery and then transported into the CNS, are important in clearing RABV from the CNS. In the present study, mouse serum containing VNA was administered intravenously into mice after infection with wild-type RABV. Our studies demonstrate that exogenous administration of VNAs is crucial in the clearance of RABV from the brain and prevent the development of rabies in both immunocompetent and immunocompromised mice as long as the BBB permeability remains enhanced. This present study therefore provides a foundation for the possibility of developing VNA therapy for clinical rabies in humans.
authors.affiliation: Department of Pathology, University of Georgia, Athens, GA 30602, USA.
authors.forename: Chien-Tsun
authors.initials: CT
authors.lastname: Huang
authors.affiliation: Department of Pathology, University of Georgia, Athens, GA 30602, USA; State Key Laboratory of Special Economic Animal Molecular Biology, Institute of Special Economic Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, Jilin 130122, China.
authors.forename: Zhenguang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pathology, University of Georgia, Athens, GA 30602, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Pathology, University of Georgia, Athens, GA 30602, USA.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Pathology, University of Georgia, Athens, GA 30602, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Pathology, University of Georgia, Athens, GA 30602, USA.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Chai
authors.affiliation: State Key Laboratory of Special Economic Animal Molecular Biology, Institute of Special Economic Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, Jilin 130122, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Pathology, University of Georgia, Athens, GA 30602, USA; State Key Laboratory of Agricultural Microbiology, Key Laboratory of Development of Veterinary Diagnostic Products, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China. Electronic address: zhenfu@uga.edu.
authors.forename: Zhen F
authors.initials: ZF
authors.lastname: Fu
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000276:immunology; D000914:Antibodies, Viral / Q000008:administration & dosage / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000276:immunology / Q000821:virology; D018932:Chemokine CCL2 / Q000276:immunology / Q000494:pharmacology*; D005260:Female; D007106:Immune Sera / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D007116:Immunization, Passive; D051379:Mice; D008813:Mice, Inbred ICR; D010539:Permeability / Q000187:drug effects; D011818:Rabies / Q000276:immunology / Q000517:prevention & control*; D011820:Rabies virus / Q000276:immunology / Q000472:pathogenicity; D019108:Tight Junctions / Q000187:drug effects
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D007106:Immune Sera
keywords: BBB (blood–brain barrier); Claudin-5; MCP-1; Occludin; Rabies virus; VNA (virus-neutralizing antibody)
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