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Animal Models of Tuberculosis: An Overview

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  • Authors: Ann Williams1, Ian M. Orme2
  • Editors: William R. Jacobs Jr.3, Helen McShane4, Valerie Mizrahi5, Ian M. Orme6
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Health UK, Porton Down SP4 0JG, United Kingdom; 2: Colorado State University, Fort Collins, CO 80523; 3: Howard Hughes Medical Institute, Albert Einstein School of Medicine, Bronx, NY 10461; 4: University of Oxford, Oxford OX3 7DQ, United Kingdom; 5: University of Cape Town, Rondebosch 7701, South Africa; 6: Colorado State University, Fort Collins, CO 80523
  • Source: microbiolspec July 2016 vol. 4 no. 4 doi:10.1128/microbiolspec.TBTB2-0004-2015
  • Received 25 November 2015 Accepted 05 January 2016 Published 01 July 2016
  • Ian M. Orme, ian.orme@colostate.edu
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  • Abstract:

    This article provides an overview of the animal models currently used in tuberculosis research, both for understanding the basic science of the disease process and also for practical issues such as testing new vaccine candidates and evaluating the activity of potential new drugs. Animals range in size, from zebrafish to cattle, and in degrees of similarity to the human disease from both an immunological and pathologic perspective. These models have provided a great wealth of information (impossible to obtain simply from observing infected humans), but we emphasize here that one must use care in interpreting or applying this information, and indeed the true art of animal modeling is in deciding what is pertinent information and what might not be. These ideas are discussed in the context of current approaches in vaccine and drug development, including a discussion of certain limitations the field is currently facing in such studies.

  • Citation: Williams A, Orme I. 2016. Animal Models of Tuberculosis: An Overview. Microbiol Spectrum 4(4):TBTB2-0004-2015. doi:10.1128/microbiolspec.TBTB2-0004-2015.

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/content/journal/microbiolspec/10.1128/microbiolspec.TBTB2-0004-2015
2016-07-01
2017-09-20

Abstract:

This article provides an overview of the animal models currently used in tuberculosis research, both for understanding the basic science of the disease process and also for practical issues such as testing new vaccine candidates and evaluating the activity of potential new drugs. Animals range in size, from zebrafish to cattle, and in degrees of similarity to the human disease from both an immunological and pathologic perspective. These models have provided a great wealth of information (impossible to obtain simply from observing infected humans), but we emphasize here that one must use care in interpreting or applying this information, and indeed the true art of animal modeling is in deciding what is pertinent information and what might not be. These ideas are discussed in the context of current approaches in vaccine and drug development, including a discussion of certain limitations the field is currently facing in such studies.

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FIGURE 1

The theoretical relationship among virulence, immunogenicity, and fitness, and its importance in the assessment of vaccine efficacy. In assessing whether a vaccine is active, the vaccine to challenge (or boost) interval is critical. In most protocols, this interval is relatively short, and so a boosting candidate, or the challenge infection itself, is given before the effector immune response has completely contracted and the subsequent memory immune response (the true target) has become fully established. After challenge, the change in CFU levels versus time indicates the intrinsic virulence of the strain used. If the vaccine has induced memory immunity, the growth of the challenge infection is slowed, but the rapidity with which this happens also depends on the immunogenicity of the organism. Finally, recent studies (see reference 18 , for example) indicate that certain clinical strains, despite high virulence, are very effectively controlled by BCG vaccination, suggesting low fitness, whereas others are transiently inhibited but after a while continue to grow progressively.

Source: microbiolspec July 2016 vol. 4 no. 4 doi:10.1128/microbiolspec.TBTB2-0004-2015
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