Tuberculosis (TB) is a global infectious disease caused by the Mycobacterium tuberculosis complex. The number of deaths caused by TB is second only to COVID-19. Therefore, vaccination plays an essential role in the prevention and control of TB. However, the efficacy of currently licensed TB vaccine, bacilli Calmette-Guérin (BCG), varies from 0%-80% in adults, and the protection only lasts for 10-15 years. Thus, there is an urgent need to develop advanced TB vaccines against TB infections.

According to Global Tuberculosis Report 2020 released by the WHO, more than 14 vaccine candidates have been evaluated in clinical trials, including 3 vaccines in Phase I, 9 in Phase II, and 2 in Phase III. Based on the principle of design, vaccines can be divided into four categories: viral vector vaccines, subunit vaccines, inactivated vaccines, and live attenuated vaccines.

Recently, it has been reported that M72/AS01E candidate is promising. However, there are still significant challenges in the development of effective vaccines against TB infection, such as unclear pathogenic mechanism of M. tuberculosis, poor understanding of the immune balance between bacterial pathogenicity and the host immunity, and unsatisfactory protection rate in clinical trials. In addition, we need to develop better animal models that can accurately predict the heterogeneity of the immune response against M. tuberculosis in human, and to find new markers to efficiently evaluate vaccine efficacy.

Noticeably, as COVID-19 continues threatening people's lives and health globally, the co-infection of TB and COVID-19 exacerbates patients' clinical symptoms and increases the mortality. On the other hand, a growing number of studies have indicated that the “trained immunity” induced by the BCG vaccine may protect people from SARS-CoV-2 infection. However, the underlying mechanism of the induction of the “trained immunity” and its sustained memory is still yet to be investigated. More clinical trials are needed to study the effectiveness of the BCG vaccine against COVID-19 or co-infection with COVID-19 and TB.

This research topic hopes to provide an overview of the innate and adaptive immune responses during M. tuberculosis infection and present the latest progress of novel TB vaccine development. We welcome Original Research, Clinical Trial, Mini-review, Review, Systematic Review, and Opinion related to the immune mechanism of TB, immune balance between M. tuberculosis and the host, and the latest progress of new TB vaccines in pre-clinical studies or clinical trials, as well as the relationship between COVID-19 and BCG vaccination. The collection of articles will include, but not limited to, the following subtopics:

（1） Novel discovery and theory on the immune mechanism of M. tuberculosis infection, and immunotherapeutic vaccines against Tuberculosis (TB).
（2） Better understanding of the immune balance between bacterial pathogenicity and the host immunity, and immune mechanisms of trained immunity induced by bacilli Calmette-Guérin (BCG) vaccine.
（3） The potential protective effect of the vaccine BCG on the prevention of COVID-19.
（4） Novel TB vaccines and their protective mechanisms in pre-clinical and clinical studies, especially the vaccines based on new technologies or antigens.
（5） Novel approaches to improve the protection rate of TB vaccines in clinical trials.
（6） Animal models that more accurately predict the heterogeneity of the immune response against M. tuberculosis in humans.
（7） Identification of new markers related to predicting vaccine efficacy and adjuvants used in TB vaccine research and development.

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Frontiers in Immunology

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