Tuberculosis Vaccines and Novel Drug Development

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Microbiology in Human Health and Disease".

Deadline for manuscript submissions: closed (31 December 2024) | Viewed by 1692

Special Issue Editors


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Guest Editor
Department of Biological Sciences, University of Texas at El Paso, El Paso, TX 79968, USA
Interests: tuberculosis vaccines; tuberculosis chemotherapy and drug development; mycobacterium tuberculosis pathogenesis; host directed therapies; BCG induced trained immunity
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Guest Editor
Division of Pulmonary and Critical Care Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, USA
Interests: tuberculosis; mycobacteria; Interleukin-17; Th-17 cytokines; matrix metalloproteinase; intracellular signaling; microbiome; host immune response

Special Issue Information

Dear Colleagues,

Tuberculosis (TB) continues to be a major global health burden and kills over a million people annually. The emergence of drug-resistant strains has further worsened the situation that demands urgent need for vaccines and novel drug development against Mycobacterium tuberculosis (Mtb). The attenuated Mycobacterium bovis strain Bacille Calmette–Guerin (BCG) is the only FDA-licensed TB vaccine. BCG protects infants against disseminated TB, but it shows variable protection against adult pulmonary TB. Moreover, BCG can disseminate under immunosuppressed or immunocompromised conditions; hence, a safer and more efficacious TB vaccine is paramount. This requires a better understanding of the mechanisms that Mtb deploys to evade the host immune response.

Prolonged treatment regimens and poor drug compliance have led to the emergence of drug resistant strains and have thwarted international efforts to control this pandemic. A robust pipeline of new TB drug discovery and development is required for the successful development of new regimens. The recent second wave of anti-TB drug development that included Bedaquiline, Delamanid and Pretomanid offers the potential for shorter regimens and has been the driving force behind several translational studies and clinical trials in recent years. Finally, TB eradication programs suffered a major setback during the COVID-19 pandemic, and it is now time to join forces again in a concerted manner so that we can eradicate this scourge.

This Special Issue welcomes all types of manuscripts providing insight into aspects relevant to TB vaccines and novel drug development. We are interested in a wide scope of work including but not limited to basic science research and clinical studies. We welcome the submission of original articles, reviews and other research articles that will improve our knowledge in these areas. 

Dr. Sangeeta Tiwari
Dr. Shivani Singh
Guest Editors

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Keywords

  • tuberculosis vaccine
  • recombinant BCG
  • BCG prime boost regimens
  • drug-resistant TB
  • second-line TB drugs

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Published Papers (1 paper)

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Research

12 pages, 607 KiB  
Article
Boosting Immunogenicity of a Recombinant Mycobacterium smegmatis Strain via Zinc-Dependent Ribosomal Proteins
by Shivani Singh, David Kanzin, Sarah Chavez, Noemi Alejandra Saavedra-Avila, Tony W. Ng, Regy Lukose, Oren Mayer, John Kim, Bing Chen, Mei Chen, Steven A. Porcelli, William R. Jacobs, Jr. and Sangeeta Tiwari
Biomedicines 2024, 12(7), 1571; https://doi.org/10.3390/biomedicines12071571 - 15 Jul 2024
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Abstract
Tuberculosis (TB) continues to be a major global health burden and kills over a million people annually. New immunization strategies are required for the development of an efficacious TB vaccine that can potentially induce sterilizing immunity. In this study, we first confirmed that [...] Read more.
Tuberculosis (TB) continues to be a major global health burden and kills over a million people annually. New immunization strategies are required for the development of an efficacious TB vaccine that can potentially induce sterilizing immunity. In this study, we first confirmed that a live vaccine strain of Mycobacterium smegmatis, previously designated as IKEPLUS, conferred a higher survival benefit than the Bacillus Calmette-Guerin (BCG) in a murine model of intravenous Mycobacterium tuberculosis (Mtb) infection. We have shown that there was a significant increase in the expression of the Rv0282 gene, which is encoded in the esx-3 locus, which played an important role in iron uptake when IKEPLUS was grown in both low zinc and iron-containing Sauton medium. We then confirmed using in vitro assays of biofilm formation that zinc plays a vital role in the growth and formation of M. smegmatis biofilms. IKEPLUS grown in low zinc media led to the better protection of mice after intravenous challenge with a very high dosage of Mtb. We also showed that various variants of IKEPLUS induced apoptotic cell-death of infected macrophages at a higher rate than wild-type M. smegmatis. We next attempted to determine if zinc containing ribosomal proteins such as rpmb2 could contribute to protective efficacy against Mtb infection. Since BCG has an established role in anti-mycobacterial efficacy, we boosted BCG vaccinated mice with rmpb2, but this did not lead to an increment in the protection mediated by BCG. Full article
(This article belongs to the Special Issue Tuberculosis Vaccines and Novel Drug Development)
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