Abstract
This pilot study aimed to determine the utility of a cynomolgus macaque model of coinfection with simian immunodeficiency virus (SIV) for the assessment of vaccines designed to prevent reactivation of TB. Following infection caused by aerosol exposure to an ultralow dose of Mycobacterium tuberculosis (M. tb), data trends indicated that subsequent coinfection with SIVmac32H perturbed control of M. tb infection as evidenced by the increased occurrence of progressive disease in this group, higher levels of pathology and increased frequency of progressive tuberculous granulomas in the lung. BCG vaccination led to improved control of TB-induced disease and lower viral load in comparison to unvaccinated coinfected animals. The M. tb-specific IFNγ response after exposure to M. tb, previously shown to be associated with bacterial burden, was lower in the BCG-vaccinated group than in the unvaccinated groups. Levels of CD4+ and CD8+ T cells decreased in coinfected animals, with counts recovering more quickly in the BCG-vaccinated group. This pilot study provides proof of concept to support the use of the model for evaluation of interventions against reactivated/exacerbated TB caused by human immunodeficiency virus (HIV) infection.
Highlights
TB is one of the leading causes of human deaths from a single infectious agent worldwide
Reactivation is hard to model in macaques because TB disease is slow to manifest and the models that currently exist need to run for a long period of time [11]
A spectrum of outcomes can occur following infection, from progressive disease to latency, and this lack of consistency in infection outcome reduces the practicality for testing novel interventions
Summary
TB is one of the leading causes of human deaths from a single infectious agent worldwide. Of which were people coinfected with human immunodeficiency virus (HIV) [1] During this period, TB was responsible for 1.4 million deaths, of which approximately 0.2 million deaths were among HIV-positive people [1]. 2 billion people are estimated to be infected with TB, and 5–10% of these individuals are at high risk of relapsing to infectious active disease during their lifetime [1]. This risk is believed to be increased for those infected with HIV [2,3]. TB disease is exacerbated following coinfection with HIV because the immune response to
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