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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.
AuthorsChien-Tsun Huang, Zhenguang Li, Ying Huang, Guoqing Zhang, Ming Zhou, Qingqing Chai, Hua Wu, Zhen F Fu
JournalAntiviral research (Antiviral Res) Vol. 110 Pg. 132-41 (Oct 2014) ISSN: 1872-9096 [Electronic] Netherlands
PMID25108172 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2014 Elsevier B.V. All rights reserved.
Chemical References
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Immune Sera
Topics
  • Animals
  • Antibodies, Neutralizing (administration & dosage, immunology)
  • Antibodies, Viral (administration & dosage, immunology)
  • B-Lymphocytes (immunology)
  • Biological Transport (drug effects)
  • Blood-Brain Barrier (physiology)
  • Brain (immunology, virology)
  • Chemokine CCL2 (immunology, pharmacology)
  • Female
  • Immune Sera (administration & dosage, immunology, pharmacology)
  • Immunization, Passive
  • Mice
  • Mice, Inbred ICR
  • Permeability (drug effects)
  • Rabies (immunology, prevention & control)
  • Rabies virus (immunology, pathogenicity)
  • Tight Junctions (drug effects)

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