Animal Models of Tuberculosis Vaccine Research: An Important Component in the Fight against Tuberculosis

Abstract

Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis, is one of the top ten infectious diseases worldwide, and is the leading cause of morbidity from a single infectious agent. M. tuberculosis can cause infection in several species of animals in addition to humans as the natural hosts. Although animal models of TB disease cannot completely simulate the occurrence and development of human TB, they play an important role in studying the pathogenesis, immune responses, and pathological changes as well as for vaccine research. This review summarizes the commonly employed animal models, including mouse, guinea pig, rabbit, rat, goat, cattle, and nonhuman primates, and their characteristics as used in TB vaccine research, and provides a basis for selecting appropriate animal models according to specific research needs. Furthermore, some of the newest animal models used for TB vaccine research (such as humanized animal models, zebrafish, Drosophila, and amoeba) are introduced, and their characteristics and research progress are discussed.

Figure 1

Statistical map of the utilization of different animal models in preclinical studies of TB vaccines. The source of the publications was an NCBI (National Center for Biotechnology Information) PubMed search using the keywords (vaccine AND tuberculosis AND ten categories shown in figure). The statistics were plotted using an open source graph visualization and manipulation software termed Gehpi. Each study is represented by a blue dot, and each animal model is represented by a circle of different color. The circle size represents the frequency of use of the animal model.

Figure 2

Tubercles of spleen or lung collected from guinea pigs or mice infected with M. tuberculosis H37Rv strain. BALB/c mice or guinea pigs were challenged with M. tuberculosis H37Rv strain (2 × 10⁵ CFUs or 5 × 10³ CFUs) to construct M. tuberculosis infected mouse or guinea pig TB model, respectively. After 3 days or 1 week, mice or guinea pigs were immunized intramuscularly three times at 2-weeks intervals with M. tuberculosis Ag85A/B chimeric DNA vaccine (vaccine group) or normal saline (negative control), respectively. Three weeks after last immunization, the mice or guinea pigs were sacrificed and their spleen and lung were collected to observe pathological lesions.