High-throughput automated image analysis of neuroinflammation and neurodegeneration enables quantitative assessment of virus neurovirulence

Vaccine. 2010 Dec 6;28(52):8315-26. doi: 10.1016/j.vaccine.2010.07.070. Epub 2010 Aug 3.

Abstract

Historically, the safety of live attenuated vaccine candidates against neurotropic viruses was assessed by semi-quantitative analysis of virus-induced histopathology in the central nervous system of monkeys. We have developed a high-throughput automated image analysis (AIA) for the quantitative assessment of virus-induced neuroinflammation and neurodegeneration. Evaluation of the results generated by AIA showed that quantitative estimates of lymphocytic infiltration, microglial activation, and neurodegeneration strongly and significantly correlated with results of traditional histopathological scoring. In addition, we show that AIA is a targeted, objective, accurate, and time-efficient approach that provides reliable differentiation of virus neurovirulence. As such, it may become a useful tool in establishing consistent analytical standards across research and development laboratories and regulatory agencies, and may improve the safety evaluation of live virus vaccines. The implementation of this high-throughput AIA will markedly advance many fields of research including virology, neuroinflammation, neuroscience, and vaccinology.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Automation / methods*
  • Dengue Virus / pathogenicity
  • Encephalitis Viruses, Tick-Borne / pathogenicity
  • High-Throughput Screening Assays / methods*
  • Histocytochemistry
  • Image Processing, Computer-Assisted / methods*
  • Macaca mulatta
  • Microscopy
  • Nervous System Diseases / pathology*
  • Nervous System Diseases / prevention & control
  • Nervous System Diseases / virology
  • Primate Diseases / pathology*
  • Primate Diseases / prevention & control
  • Primate Diseases / virology
  • Virus Diseases / pathology*
  • Virus Diseases / prevention & control