Abstract

The widely administered tuberculosis (TB) vaccine, Bacillus Calmette-Guerin (BCG), is the only licensed vaccine, but has highly variable efficiency against childhood and pulmonary TB. Therefore, the BCG prime-boost strategy is a rational solution for the development of new TB vaccines. Studies have shown that Mycobacterium tuberculosis (Mtb) culture filtrates contain proteins that have promising vaccine potential. In this study, Rv1876 bacterioferritin was identified from the culture filtrate fraction with strong immunoreactivity. Its immunobiological potential has not been reported previously. We found that recombinant Rv1876 protein induced dendritic cells’ (DCs) maturation by MAPK and NF-κB signaling activation, induced a T helper type 1 cell-immune response, and expanded the population of the effector/memory T cell. Boosting BCG with Rv1876 protein enhanced the BCG-primed Th1 immune response and reduced the bacterial load in the lung compared to those of BCG alone. Thus, Rv1876 is a good target for the prime-boost strategy.

Highlights

  • Tuberculosis (TB) remains a global health priority, with an estimated 2 billion people infected, according to the Global Tuberculosis Report, 2020

  • ion-exchange chromatography (IEC) fraction number 70 of the hydroxyapatite chromatography (HAT) pass fraction from the initial fraction 5 was further fractionated by the whole gel eluter (Figure 1Ab)

  • We found that the MAPK and NF-κB signaling pathways are required for dendritic cells’ (DCs) maturation and activation by the Rv1876 protein

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Summary

Introduction

Tuberculosis (TB) remains a global health priority, with an estimated 2 billion people infected, according to the Global Tuberculosis Report, 2020. HIV infection, increase in immunosuppressive drug application, reactivation of latent TB, and the emergence of multidrug-resistant TB has complicated TB control. The only licensed vaccine, Mycobacterium bovis bacillus Calmette–Guérin (BCG), has highly variable efficiency in children, and is often ineffective in adults [1]. A safer and more effective vaccine to replace. BCG or BCG-prime boosting is urgently required. After the World Health Organization (WHO) declared COVID-19 a pandemic, public health services, including TB services, were suspended in almost all countries. TB and COVID-19 are airborne diseases that primarily attack the lungs, but TB has a longer incubation period and a slower disease onset.

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