Combination drug treatment prolongs survival of experimentally infected mice with silver-haired bat rabies virus

Vaccine. 2019 Aug 2;37(33):4736-4742. doi: 10.1016/j.vaccine.2018.05.065. Epub 2018 May 26.

Abstract

Rabies is a lethal disease in humans and animals, killing approximately 60,000 people every year. Currently, there is no treatment available, except post-exposure prophylaxis (PEP) that can be administered whenever exposure to a rabid animal took place. Here we describe the beneficial effects of a combination treatment initiated at day 4 post infection, containing anti-viral drugs and immune modulators in infected mice. Combination therapy resulted in significant increase in survival time (P < 0.05) and significantly lowers viral RNA in the brain and spinal cord (P < 0.05). Furthermore, treatment influenced markers of pyroptosis and apoptosis and early inflammatory response as measured by the levels of TNF-α. Morphological lesions were absent in rabies virus infected mice with few signs of inflammation. However, these were not significant between the different groups.

Keywords: Blood–brain barrier; Combination treatment; Rabies; Therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Brain / metabolism
  • Brain / virology
  • Cell Line, Tumor
  • Chiroptera
  • Female
  • Infliximab / therapeutic use
  • Mannitol / therapeutic use
  • Mice
  • Mice, Inbred C57BL
  • Post-Exposure Prophylaxis
  • Pyroptosis / physiology
  • RNA, Viral / genetics
  • Rabies / drug therapy*
  • Rabies / virology
  • Sorafenib / therapeutic use
  • Spinal Cord / metabolism
  • Spinal Cord / virology

Substances

  • RNA, Viral
  • Mannitol
  • Sorafenib
  • Infliximab