Rapid, non-invasive imaging of alphaviral brain infection

Reducing animal numbers and morbidity to identify efficacy of potential vaccines and antivirals

Michael Patterson, Allison Poussard, Katherine Taylor, Alexey Seregin, Jeanon Smith, Bihung Peng, Aida Walker, Jenna Linde, Jennifer Smith, Milagros Salazar, Slobodan Paessler

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Rapid and accurate identification of disease progression are key factors in testing novel vaccines and antivirals against encephalitic alphaviruses. Typical efficacy studies utilize a large number of animals and severe morbidity or mortality as an endpoint. New technologies provide a means to reduce and refine the animal use as proposed in Hume's 3Rs (replacement, reduction, refinement) described by Russel and Burch. . In vivo imaging systems (IVIS) and bioluminescent enzyme technologies accomplish the reduction of animal requirements while shortening the experimental time and improving the accuracy in localizing active virus replication. In the case of murine models of viral encephalitis in which central nervous system (CNS) viral invasion occurs rapidly but the disease development is relatively slow, we visualized the initial brain infection and enhance the data collection process required for efficacy studies on antivirals or vaccines that are aimed at preventing brain infection. Accordingly, we infected mice through intranasal inoculation with the genetically modified pathogen, Venezuelan equine encephalitis, which expresses a luciferase gene. In this study, we were able to identify the invasion of the CNS at least 3 days before any clinical signs of disease, allowing for reduction of animal morbidity providing a humane means of disease and vaccine research while obtaining scientific data accurately and more rapidly. Based on our data from the imaging model, we confirmed the usefulness of this technology in preclinical research by demonstrating the efficacy of Ampligen, a TLR-3 agonist, in preventing CNS invasion.

Original languageEnglish (US)
Pages (from-to)9345-9351
Number of pages7
JournalVaccine
Volume29
Issue number50
DOIs
StatePublished - Nov 21 2011

Fingerprint

Neuroimaging
Antiviral Agents
morbidity
Vaccines
image analysis
vaccines
central nervous system
Morbidity
brain
Central Nervous System
Infection
Technology
infection
animals
Venezuelan Equine Encephalomyelitides
viral encephalitis
Viral Encephalitis
Alphavirus
Brain
luciferase

Keywords

  • Encephalitis
  • In vivo
  • IVIS
  • Luciferase
  • Neuroinvasion
  • TC83
  • VEEV

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

Cite this

Rapid, non-invasive imaging of alphaviral brain infection : Reducing animal numbers and morbidity to identify efficacy of potential vaccines and antivirals. / Patterson, Michael; Poussard, Allison; Taylor, Katherine; Seregin, Alexey; Smith, Jeanon; Peng, Bihung; Walker, Aida; Linde, Jenna; Smith, Jennifer; Salazar, Milagros; Paessler, Slobodan.

In: Vaccine, Vol. 29, No. 50, 21.11.2011, p. 9345-9351.

Research output: Contribution to journalArticle

Patterson, M, Poussard, A, Taylor, K, Seregin, A, Smith, J, Peng, B, Walker, A, Linde, J, Smith, J, Salazar, M & Paessler, S 2011, 'Rapid, non-invasive imaging of alphaviral brain infection: Reducing animal numbers and morbidity to identify efficacy of potential vaccines and antivirals', Vaccine, vol. 29, no. 50, pp. 9345-9351. https://doi.org/10.1016/j.vaccine.2011.09.130
Patterson, Michael ; Poussard, Allison ; Taylor, Katherine ; Seregin, Alexey ; Smith, Jeanon ; Peng, Bihung ; Walker, Aida ; Linde, Jenna ; Smith, Jennifer ; Salazar, Milagros ; Paessler, Slobodan. / Rapid, non-invasive imaging of alphaviral brain infection : Reducing animal numbers and morbidity to identify efficacy of potential vaccines and antivirals. In: Vaccine. 2011 ; Vol. 29, No. 50. pp. 9345-9351.
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