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The T cell immune response against latent infection with Mycobacterium tuberculosis

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Revisiting tuberculosis vaccination

Vaccination against tuberculosis is largely inefficient as immune responses fail to eradicate the bacteria. European scientists proposed novel approaches for enhancing immune responses against Mycobacterium tuberculosis (Mtb) based on disease latency.

Health

Tuberculosis is an active health threat accounting for millions of deaths every year. To make matters worse, nearly one third of the population are infected with latent tuberculosis. During this chronic infection, Mtb is controlled by T cell-mediated immune responses against dominant bacterial epitopes. Around 5 % of latent-infected patients will develop active tuberculosis at some point, indicating that their immune system is unable to fully eradicate the bacteria. Also, the epitopes targeted by the immune system are conserved among Mtb strains, suggesting that T cell activation may benefit bacterial survival and persistence. The EU-funded 'The T cell immune response against latent infection with Mycobacterium tuberculosis' (TILIM) project worked to develop vaccines that target subdominant Mtb epitopes for disease eradication. They defined subdominant epitopes as parts of the protein that are not targeted during Mtb infection alone. To achieve this, scientists vaccinated animals with different polypeptides to generate subdominant-specific T cell immune responses. They successfully identified subdominant epitopes capable of inducing prophylaxis against Mtb infection. Following Mtb infection of vaccinated animals, the subdominant-specific T cells presented with an enhanced cytokine pattern and a memory-like, protective phenotype. Similar responses are seen in vaccine-induced dominant-specific T cells but this is accompanied by a terminally differentiated phenotype associated with Mtb-driven exhaustion. In contrast, the subdominant-specific T cells were not as differentiated and had significantly higher memory-like phenotype. This was also true when vaccines contained both dominant and subdominant peptides, indicating that the differential T cell development during Mtb infection was not due to disease development. The findings of the TILIM project have strong clinical implications, clearly demonstrating the potential for inducing T cell responses against subdominant Mtb peptides. This information should be incorporated in the design of future vaccines to eradicate tuberculosis.

Keywords

Tuberculosis, vaccination, Mycobacterium tuberculosis, latent tuberculosis, T cell, subdominant epitope, cytokine, phenotype

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8 February 2023