The minipig as an animal model to study Mycobacterium tuberculosis infection and natural transmission

Ramos, Laylaa; Obregón-Henao, Andrés; Henao-Tamayo, Marcela; Bowen, Richard A.; Lunney, Joan K.; Gonzalez-Juarrero, Mercedes

doi:10.1016/j.tube.2017.07.003

Cited by 26 publications

(26 citation statements)

References 27 publications

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“…Minipigs are a genetically selected species, which is more convenient than other pigs for experiments in a lab, mainly for size reasons. Experimental results in TB in minipigs resemble pathological findings described in human [21][22][23].…”

Section: Plos Computational Biologysupporting

confidence: 61%

Modelling the dynamics of tuberculosis lesions in a virtual lung: Role of the bronchial tree in endogenous reinfection

et al. 2020

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Tuberculosis (TB) is an infectious disease that still causes more than 1.5 million deaths annually. The World Health Organization estimates that around 30% of the world's population is latently infected. However, the mechanisms responsible for 10% of this reserve (i.e., of the latently infected population) developing an active disease are not fully understood, yet. The dynamic hypothesis suggests that endogenous reinfection has an important role in maintaining latent infection. In order to examine this hypothesis for falsifiability, an agentbased model of growth, merging, and proliferation of TB lesions was implemented in a computational bronchial tree, built with an iterative algorithm for the generation of bronchial bifurcations and tubes applied inside a virtual 3D pulmonary surface. The computational model was fed and parameterized with computed tomography (CT) experimental data from 5 latently infected minipigs. First, we used CT images to reconstruct the virtual pulmonary surfaces where bronchial trees are built. Then, CT data about TB lesion' size and location to each minipig were used in the parameterization process. The model's outcome provides spatial and size distributions of TB lesions that successfully reproduced experimental data, thus reinforcing the role of the bronchial tree as the spatial structure triggering endogenous reinfection. A sensitivity analysis of the model shows that the final number of lesions is strongly related with the endogenous reinfection frequency and maximum growth rate of the lesions, while their mean diameter mainly depends on the spatial spreading of new lesions and the maximum radius. Finally, the model was used as an in silico experimental platform to explore the transition from latent infection to active disease, identifying two main triggering factors: a high inflammatory response and the combination of a moderate inflammatory response with a small breathing amplitude.

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Section: Plos Computational Biologysupporting

confidence: 61%

Modelling the dynamics of tuberculosis lesions in a virtual lung: Role of the bronchial tree in endogenous reinfection

et al. 2020

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“…M. tuberculosis can be transmitted not only between humans and animals but also between animals through similar transmission routes found in humans. Ramos et al [207] reported that when W-Beijing M. tuberculosis HN878 infected or unchallenged minipigs were housed together, active M. tuberculosis could be identified in the pulmonary and thoracic lymph nodes from both infected and unchallenged minipigs. Furthermore, it is gradually becoming recognized that vaccination of domestic animals may be an alternative long-term strategy for controlling the transmission of TB [208].…”

Section: New Technologies and Tools Open New Avenues For The Use Of Amentioning

confidence: 99%

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

Gong

Liang

2020

BioMed Research International

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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.

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“…Overall, these studies prove the potential pigs have for modeling TB. Upon Mtb infection, pigs develop similar pathological changes in the lung tissue and parenchyma to humans, including pulmonary tubercles with caseous necrosis, followed by liquefaction and cavity formation (Ramos et al, 2019;Helke et al, 2006), and mount immune responses that recapitulate the human response to Mtb infection and BCG vaccination (Gil et al, 2010;Lee et al, 2004;Ramos et al, 2019;Ramos et al, 2017). This, combined with their size and anatomy ( Table 2), affirms that neonatal pigs are suitable models for neonatal and infant human TB vaccine research.…”

Section: Pigsmentioning

confidence: 73%

“…Our group used an aerosol route to infect 2-month-old and 6month-old miniature pigs, representing the respective human infancy and adolescence, with the hypervirulent strain Mtb HN878 (Ramos et al, 2017). We observed pathological changes, such as caseous necrosis and calcified lesions in the lungs and lymph nodes, recovered viable bacteria from both tissues, and demonstrated natural aerosol transmission from infected to uninfected pigs housed together (Ramos et al, 2017). Further, our group studied the immune response of neonatal piglets that were vaccinated with BCG at birth and challenged with MtB at 20 weeks of life (Ramos et al, 2019).…”

Section: Pigsmentioning

confidence: 99%

“…The Th1 response to the Mtb fragment-based vaccine in these pigs further supports their use as vaccine models, as human infants predominantly mount a Th1 response to BCG ( Marchant et al, 1999 ). Our group used an aerosol route to infect 2-month-old and 6-month-old miniature pigs, representing the respective human infancy and adolescence, with the hypervirulent strain Mtb HN878 ( Ramos et al, 2017 ). We observed pathological changes, such as caseous necrosis and calcified lesions in the lungs and lymph nodes, recovered viable bacteria from both tissues, and demonstrated natural aerosol transmission from infected to uninfected pigs housed together ( Ramos et al, 2017 ).…”

Section: Pigsmentioning

confidence: 99%

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Neonatal and infant immunity for tuberculosis vaccine development: importance of age-matched animal models

Ramos

Lunney

Gonzalez-Juarrero

2020

Disease Models &Amp; Mechanisms

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Neonatal and infant immunity differs from that of adults in both the innate and adaptive arms, which are critical contributors to immune-mediated clearance of infection and memory responses elicited during vaccination. The tuberculosis (TB) research community has openly admitted to a vacuum of knowledge about neonatal and infant immune responses to Mycobacterium tuberculosis (Mtb) infection, especially in the functional and phenotypic attributes of memory T cell responses elicited by the only available vaccine for TB, the Bacillus Calmette–Guérin (BCG) vaccine. Although BCG vaccination has variable efficacy in preventing pulmonary TB during adolescence and adulthood, 80% of endemic TB countries still administer BCG at birth because it has a good safety profile and protects children from severe forms of TB. As such, new vaccines must work in conjunction with BCG at birth and, thus, it is essential to understand how BCG shapes the immune system during the first months of life. However, many aspects of the neonatal and infant immune response elicited by vaccination with BCG remain unknown, as only a handful of studies have followed BCG responses in infants. Furthermore, most animal models currently used to study TB vaccine candidates rely on adult-aged animals. This presents unique challenges when transitioning to human trials in neonates or infants. In this Review, we focus on vaccine development in the field of TB and compare the relative utility of animal models used thus far to study neonatal and infant immunity. We encourage the development of neonatal animal models for TB, especially the use of pigs.

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The minipig as an animal model to study Mycobacterium tuberculosis infection and natural transmission

Cited by 26 publications

References 27 publications

Modelling the dynamics of tuberculosis lesions in a virtual lung: Role of the bronchial tree in endogenous reinfection

Modelling the dynamics of tuberculosis lesions in a virtual lung: Role of the bronchial tree in endogenous reinfection

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

Neonatal and infant immunity for tuberculosis vaccine development: importance of age-matched animal models

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