Abstract
BackgroundNew interventions for tuberculosis are urgently needed. Non-human primate (NHP) models provide the most relevant pre-clinical models of human disease and play a critical role in vaccine development. Models utilising Asian cynomolgus macaque populations are well established but the restricted genetic diversity of the Mauritian cynomolgus macaques may be of added value.MethodsMauritian cynomolgus macaques were exposed to a range of doses of M. tuberculosis delivered by aerosol, and the outcome was assessed using clinical, imaging and pathology-based measures.ResultsAll macaques developed characteristic clinical signs and disease features of tuberculosis (TB). Disease burden and the ability to control disease were dependent on exposure dose. Mauritian cynomolgus macaques showed less variation in pulmonary disease burden and total gross pathology scores within exposure dose groups than either Indian rhesus macaques or Chinese cynomolgus macaquesConclusionsThe genetic homogeneity of Mauritian cynomolgus macaques makes them a potentially useful model of human tuberculosis.
Highlights
Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis (TB), is responsible for 9 million new infections and 1.5 million deaths each year [1]
Mauritian cynomolgus macaques were exposed to a range of doses of M. tuberculosis delivered by aerosol, and the outcome was assessed using clinical, imaging and pathologybased measures
Vaccination is widely accepted to be the most effective method for infectious disease control, and the only licenced vaccine against M. tuberculosis, Bacille Calmette-Gurein (BCG), protects children from developing severe TB disease [2], the protection afforded to adults is limited [3], and it is unsuitable for use in people whose immune system is compromised, so more effective vaccines against M. tuberculosis are desperately needed
Summary
Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis (TB), is responsible for 9 million new infections and 1.5 million deaths each year [1]. Preclinical animal models are critical to the development of new vaccines, as studies of infectious challenge can be used to predict the effectiveness of vaccines in humans and they provide the opportunity to identify and validate correlates of protection. Due to their close similarity to humans, non-human primates offer the most relevant models of human diseases, and models of M. tuberculosis have been established in both rhesus macaque (Macaca mulatta) and cynomolgus macaque (Macaca fascicularis) species [4,5,6] with cynomolgus macaques showing an improved ability to control M. tuberculosis-induced disease [7, 8]. Models utilising Asian cynomolgus macaque populations are well established but the restricted genetic diversity of the Mauritian cynomolgus macaques may be of added value
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