Novel In Vitro/Ex Vivo Animal Modeling for Filovirus Aerosol Infection
Abstract
The overall objective of this work is to develop in vitro modular systems to dissect immune responses relating to upper and lower respiratory tract. This approach simplifies the airway physiology to mucosal epithelial interfaces responsible for primary tissue immunological responses to host infections and disease pathogenesis. This report summarizes the work relating to the collaborative research effort between the military USAMRIID labs and Sanofi Pasteur, to investigate the application of the Mucosal Tissue Equivalent (MTE) module of the MIMIC system for the development of in vitro influenza and filovirus disease models. The cellular composition of the MTE module consists of human and non-human primate species of interest for filovirus infection. The research findings from the five human and four NHP MTE modules indicate non-equivalence of primary cell and cell line form and function. The primary human MTE demonstrates superior morphology, vesicle cycling and antigen presentation cell stimulation. The MTE tissue related innate response, in terms of cytokine and chemokine profiles and viral infection and defense related genes, was also not equivalent in the various MTE motifs. The NHP tissue models showed the greatest degree of permeability and varying growth rates. This developmental work is in the process of evolution into in vitro disease models. The baseline morphological and functional read-outs described in this report may serve as a guide for therapeutic development for highly pathogenic filovirus strains.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2013
- Accession Number
- ADA599970
Entities
People
- Ayesha Mahmood