Recent Developments in Mycobacteria-Based Live Attenuated Vaccine Candidates for Tuberculosis

Flores-Valdez, Mario Alberto, Kupz, Andreas, and Subbian, Selvakumar (2022) Recent Developments in Mycobacteria-Based Live Attenuated Vaccine Candidates for Tuberculosis. Biomedicines, 10 (11). 2749.

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Vaccination is an excellent approach to stimulating the host immune response and reducing human morbidity and mortality against microbial infections, such as tuberculosis (TB). Bacillus Calmette–Guerin (BCG) is the most widely administered vaccine in the world and the only vaccine approved by the World Health Organization (WHO) to protect against TB. Although BCG confers “protective” immunity in children against the progression of Mycobacterium tuberculosis (Mtb) infection into active TB, this vaccine is ineffective in protecting adults with active TB manifestations, such as multiple-, extensive-, and total-drug-resistant (MDR/XDR/TDR) cases and the co-existence of TB with immune-compromising health conditions, such as HIV infection or diabetes. Moreover, BCG can cause disease in individuals with HIV infection or other immune compromises. Due to these limitations of BCG, novel strategies are urgently needed to improve global TB control measures. Since live vaccines elicit a broader immune response and do not require an adjuvant, developing recombinant BCG (rBCG) vaccine candidates have received significant attention as a potential replacement for the currently approved BCG vaccine for TB prevention. In this report, we aim to present the latest findings and outstanding questions that we consider worth investigating regarding novel mycobacteria-based live attenuated TB vaccine candidates. We also specifically discuss the important features of two key animal models, mice and rabbits, that are relevant to TB vaccine testing. Our review emphasizes that the development of vaccines that block the reactivation of latent Mtb infection (LTBI) into active TB would have a significant impact in reducing the spread and transmission of Mtb. The results and ideas discussed here are only based on reports from the last five years to keep the focus on recent developments.

Item ID: 77610
Item Type: Article (Research - C1)
ISSN: 2227-9059
Keywords: BCG, Esx system, HIV-TB, latent tuberculosis, MTBVAC, Mycobacterium, preclinical models, vaccine
Copyright Information: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (
Date Deposited: 14 Feb 2023 23:38
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320701 Medical bacteriology @ 40%
31 BIOLOGICAL SCIENCES > 3107 Microbiology > 310701 Bacteriology @ 20%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320404 Cellular immunology @ 40%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280103 Expanding knowledge in the biomedical and clinical sciences @ 50%
20 HEALTH > 2001 Clinical health > 200104 Prevention of human diseases and conditions @ 50%
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