Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 298, Issue 12, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.jbc.2022.102596
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Funding
- fellowship of the Department of Biotechnology
- Department of Science and Technology
- Ministry of Human Resource Development
- Indian Council of Medical Research
- Council of Scientific and Industrial Research, India
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Novel vaccination strategies are crucial for controlling tuberculosis, but drug-resistant strains of Mycobacterium tuberculosis are a major obstacle. A new vaccine formulation was developed, which effectively triggered an immune response to control tuberculosis infection.
Novel vaccination strategies are crucial to efficiently control tuberculosis, as proposed by the World Health Organization un-der its flagship program End TB Strategy. However, the emer-gence of drug-resistant strains of Mycobacterium tuberculosis (Mtb), particularly in those coinfected with HIV-AIDS, consti-tutes a major impediment to achieving this goal. We report here a novel vaccination strategy that involves synthesizing a formula-tion of an immunodominant peptide derived from the Acr1 pro-tein of Mtb. This nanoformulation in addition displayed on the surface a toll-like receptor-2 ligand to offer to target dendritic cells (DCs). Our results showed an efficient uptake of such a concoction by DCs in a predominantly toll-like receptor-2-dependent pathway. These DCs produced elevated levels of nitric oxide, proinflammatory cytokines interleukin-6, interleukin-12, and tumor necrosis factor-alpha, and upregulated the surface expression of major histocompatibility complex class II molecules as well as costimulatory molecules such as CD80 and CD86. Animals injected with such a vaccine mounted a significantly higher response of effector and memory Th1 cells and Th17 cells. Furthermore, we noticed a reduction in the bacterial load in the lungs of animals challenged with aerosolized live Mtb. Therefore, our findings indicated that the described vaccine triggered pro-tective anti-Mtb immunity to control the tuberculosis infection.
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