Novel Discoveries in the Development of Vaccines against Mycobacterial Infections

A special issue of Vaccines (ISSN 2076-393X).

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 13114

Special Issue Editor

Special Issue Information

Dear Colleagues,

Pulmonary diseases due to mycobacteria cause significant morbidity and mortality to human health. Mycobacterial lung infections are caused by mycobacteria, that includes the causative-agents of tuberculosis (TB) and leprosy. There are also nontuberculous mycobacteria (NTM), ubiquitous in soil, water, and food. NTM are usually harmless to people but for unknown reasons, NTM lung infections are becoming more common in the developed world, including the United States, particularly in the Southwest (including southern California), Southeast and Hawaii. Recent epidemiological studies have shown the emergence of NTM species in causing lung diseases in humans. Although more than 170 NTM species are present in various environmental niches, only a handful, primarily Mycobacterium avium complex and M. abscessus, have been implicated in pulmonary disease. Following inhalation, NTM are phagocytosed by alveolar macrophages in the lungs. Subsequently, various immune cells are recruited from the circulation to the site of infection, which leads to granuloma formation. Although the pathophysiology of TB and NTM diseases share several fundamental cellular and molecular events, the host-susceptibility to Mycobacterium tuberculosis (Mtb) and NTM infections are different. Striking differences also exist in the disease presentation between TB and NTM cases. While NTM disease is primarily associated with bronchiectasis, this condition is rarely a predisposing factor for TB. Similarly, in Human Immunodeficiency Virus (HIV)-infected individuals, NTM disease presents as disseminated, extrapulmonary form rather than as a miliary, pulmonary disease, which is seen in Mtb infection. Active infections with NTM can lead to structural and immunological lung complications including granuloma formation, fibrosis, and T cell exhaustion, less is known about the disease course when coinfection with SARS-CoV-2 is present. Past and present research demonstrate that IL-10, TNF-α, IFN class I-III, TGF-β, IL-35, and Regulatory T cells (T-regs) are all important contributors of the characteristics of host response to mycobacterial infections. Leprosy caused by M. leprae is also an important global health concern. Endemic mostly to tropical underdeveloped and developing countries, most commonly Brazil and India, M. leprae is transmitted mainly by entry through the nasal mucosa into the upper airway, which constitutes one of the most important entry routes. M. leprae is a non-culturable, obligate intracellular pathogen that causes a chronic granulomatous infection characterized predominantly by peripheral nerve damage and prominent skin lesions known as Leprosy or Hansen’s disease. Infection of peripheral nerves by M. leprae is a hallmark of leprous neuropathy, causing sensory, motor, and autonomic disability, thus making it one of the most common causes of peripheral neuropathy worldwide. The aim of this comprehensive special issue is put together cutting-edge research findings and reviews on: 

  • Development of novel vaccines for tuberculosis, non-tuberculous mycobacteria and/or M. leprae infections
  • The recent advances in the understanding of the host immune responses against tuberculous, non-tuberculous mycobacteria and/or M. leprae infections
  • Pathogenesis in tuberculous, non-tuberculous mycobacteria and/or M. leprae infections
  • Novel therapies for non-tuberculous mycobacteria and/or M. leprae infections
  • Prevention of tuberculous, non-tuberculous mycobacteria and/or M. leprae infections
  • COVID-related disruptions in managing vaccinations against tuberculosis I look forward to receiving your contributions.

Prof. Dr. Vishwanath Venketaraman
Guest Editor

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Keywords

  • vaccine
  • adjunctive therapy
  • tuberculous mycobacteria
  • non-tuberculous mycobacteria
  • M. leprae
  • host-directed therapy

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Published Papers (3 papers)

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Review

14 pages, 1284 KiB  
Review
Role of B Cells in Mycobacterium Tuberculosis Infection
by Paul Stewart, Shivani Patel, Andrew Comer, Shafi Muneer, Uzma Nawaz, Violet Quann, Mira Bansal and Vishwanath Venketaraman
Vaccines 2023, 11(5), 955; https://doi.org/10.3390/vaccines11050955 - 6 May 2023
Cited by 7 | Viewed by 6304
Abstract
Historically, research on the immunologic response to Mycobacterium tuberculosis (M. tb) infection has focused on T cells and macrophages, as their role in granuloma formation has been robustly characterized. In contrast, the role of B cells in the pathophysiology of M. [...] Read more.
Historically, research on the immunologic response to Mycobacterium tuberculosis (M. tb) infection has focused on T cells and macrophages, as their role in granuloma formation has been robustly characterized. In contrast, the role of B cells in the pathophysiology of M. tb infection has been relatively overlooked. While T cells are well-known as an essential for granuloma formation and maintenance, B cells play a less understood role in the host response. Over the past decade, scarce research on the topic has attempted to elucidate the varying roles of B cells during mycobacterial infection, which appears to be primarily time dependent. From acute to chronic infection, the role of B cells changes with time as evidenced by cytokine release, immunological regulation, and histological morphology of tuberculous granulomas. The goal of this review is to carefully analyze the role of humoral immunity in M. tb infection to find the discriminatory nature of humoral immunity in tuberculosis (TB). We argue that there is a need for more research on the B-cell response against TB, as a better understanding of the role of B cells in defense against TB could lead to effective vaccines and therapies. By focusing on the B-cell response, we can develop new strategies to enhance immunity against TB and reduce the burden of disease. Full article
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11 pages, 953 KiB  
Review
Neutrophils in Mycobacterium tuberculosis
by Cheldon Ann Alcantara, Ira Glassman, Kevin H. Nguyen, Arpitha Parthasarathy and Vishwanath Venketaraman
Vaccines 2023, 11(3), 631; https://doi.org/10.3390/vaccines11030631 - 12 Mar 2023
Cited by 8 | Viewed by 3595
Abstract
Mycobacterium tuberculosis (M. tb) continues to be a leading cause of mortality within developing countries. The BCG vaccine to promote immunity against M. tb is widely used in developing countries and only in specific circumstances within the United States. However, current [...] Read more.
Mycobacterium tuberculosis (M. tb) continues to be a leading cause of mortality within developing countries. The BCG vaccine to promote immunity against M. tb is widely used in developing countries and only in specific circumstances within the United States. However, current the literature reports equivocal data on the efficacy of the BCG vaccine. Critical within their role in the innate immune response, neutrophils serve as one of the first responders to infectious pathogens such as M. tb. Neutrophils promote effective clearance of M. tb through processes such as phagocytosis and the secretion of destructive granules. During the adaptative immune response, neutrophils modulate communication with lymphocytes to promote a strong pro-inflammatory response and to mediate the containment M. tb through the production of granulomas. In this review, we aim to highlight and summarize the role of neutrophils during an M. tb infection. Furthermore, the authors emphasize the need for more studies to be conducted on effective vaccination against M. tb. Full article
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21 pages, 1421 KiB  
Review
Mycobacterium tuberculosis: Implications of Ageing on Infection and Maintaining Protection in the Elderly
by Victor Bonavida, Mitchell Frame, Kevin H. Nguyen, Shlok Rajurkar and Vishwanath Venketaraman
Vaccines 2022, 10(11), 1892; https://doi.org/10.3390/vaccines10111892 - 9 Nov 2022
Cited by 4 | Viewed by 2600
Abstract
Several reports have suggested that ageing negatively affects the human body resulting in the alteration of various parameters important for sufficient immune health. Although, the breakdown of innate and adaptive immunity has been hypothesized to increase an individual’s susceptibility to infections including Mycobacterium [...] Read more.
Several reports have suggested that ageing negatively affects the human body resulting in the alteration of various parameters important for sufficient immune health. Although, the breakdown of innate and adaptive immunity has been hypothesized to increase an individual’s susceptibility to infections including Mycobacterium tuberculosis (M. tb), little research has been done to bridge this gap and understand the pathophysiology underlying how ageing increases the pathogenesis of M. tb infection. Our objective was to study research from a plethora of resources to better understand the pathogenesis of ageing and its link to the human immune system. To achieve this goal, this article explores how ageing decreases the collective T-cell immune response, reduces glutathione (GSH) production, over activates the mammalian target of rapamycin (mTORC1) pathway, inhibits autophagy and mitophagy, and alters various protective genes/transcription factors. Specifically highlighting how each of these pathways cripple an individual’s immune system and increases their susceptibility from M. tb infection. Furthermore, research summarized in this article gives rise to an additional mechanism of susceptibility to M. tb infection which includes a potential defect in antigen presenting by dendritic cells rather than the T-cells response. Inflammaging has also been shown to play a role in the ageing of the immune system and can also potentially be a driving factor for increased susceptibility to M. tb infection in the elderly. In addition, this article features possible preventative strategies that could decrease infections like M. tb in this population. These strategies would need to be further explored and range from immunomodulators, like Everolimus to antioxidant supplementation through GSH intake. We have also proposed the need to research these therapies in conjunction with the administration of the BCG vaccine, especially in endemic populations, to better understand the risk contracting M. tb infection as well as ways to prevent infection in the first place. Full article
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