Dose Response of MARV/Angola Infection in Cynomolgus Macaques following IM or Aerosol Exposure

PLoS One. 2015 Sep 28;10(9):e0138843. doi: 10.1371/journal.pone.0138843. eCollection 2015.

Abstract

Marburg virus infection in humans causes a hemorrhagic disease with a high case fatality rate. Countermeasure development requires the use of well-characterized animal models that mimic human disease. To further characterize the cynomolgus macaque model of MARV/Angola, two independent dose response studies were performed using the intramuscular or aerosol routes of exposure. All animals succumbed at the lowest target dose; therefore, a dose effect could not be determined. For intramuscular-exposed animals, 100 PFU was the first target dose that was not significantly different than higher target doses in terms of time to disposition, clinical pathology, and histopathology. Although a significant difference was not observed between aerosol-exposed animals in the 10 PFU and 100 PFU target dose groups, 100 PFU was determined to be the lowest target dose that could be consistently obtained and accurately titrated in aerosol studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aerosols / administration & dosage*
  • Animals
  • Injections, Intramuscular
  • Kaplan-Meier Estimate
  • Macaca fascicularis
  • Marburg Virus Disease / blood
  • Marburg Virus Disease / virology*
  • Marburgvirus / physiology*
  • RNA, Viral / blood
  • Temperature

Substances

  • Aerosols
  • RNA, Viral

Grants and funding

This work was supported by Translational Medical Technologies and the Joint Science and Technology Office for Chemical and Biological Defense. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.