Next-Generation TB Vaccines: Progress, Challenges, and Prospects

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is a prevalent global infectious disease and a leading cause of mortality worldwide. Currently, the only available vaccine for TB prevention is Bacillus Calmette–Guérin (BCG). However, BCG demonstrates limited efficacy, particularly in adults. Efforts to develop effective TB vaccines have been ongoing for nearly a century. In this review, we have examined the current obstacles in TB vaccine research and emphasized the significance of understanding the interaction mechanism between MTB and hosts in order to provide new avenues for research and establish a solid foundation for the development of novel vaccines. We have also assessed various TB vaccine candidates, including inactivated vaccines, attenuated live vaccines, subunit vaccines, viral vector vaccines, DNA vaccines, and the emerging mRNA vaccines as well as virus-like particle (VLP)-based vaccines, which are currently in preclinical stages or clinical trials. Furthermore, we have discussed the challenges and opportunities associated with developing different types of TB vaccines and outlined future directions for TB vaccine research, aiming to expedite the development of effective vaccines. This comprehensive review offers a summary of the progress made in the field of novel TB vaccines.

Mycobacterium tuberculosis: immune response, biomarkers, and therapeutic intervention

“…The majority of infected individuals exhibit no symptoms and are classified as having LTBI. Without treatment, around 5−10% of LTBI patients will develop TB over their lifetime, emphasizing the importance of treating LTBI to prevent disease progression 9,150,151 . The Guidelines for the Treatment of Latent Tuberculosis Infection: Recommendations from the National Tuberculosis Controllers Association and CDC guide LTBI treatment.…”

“…: (1999) S‐03) and was approved by the China Food and Drug Administration as a vaccine for adjunctive treatment of TB (Approval No. : S20010003) 8,9,241 . Originally produced by Anhui Zhifei Longcom Biologic Pharmacy Co. Ltd. (now Anhui Zhifei Biopharmaceutical Co. Ltd.), Vaccae™ has played an important role in enhancing immunity, promoting phagocytosis, regulating bidirectional immune responses, and reducing pathological damage.…”

“…The outcome of MTB infection is closely related to the strength of the host's immune system. The human immune system plays a crucial role in immune surveillance, defense, and regulation, recognizing and eliminating invading pathogens and viruses to maintain homeostasis 7–9 . The immune response to MTB antigens can be divided into two categories: innate immunity (also known as a nonspecific or natural immune response) and adaptive immunity (also known as an acquired or specific immune response).…”

“…The human immune system plays a crucial role in immune surveillance, defense, and regulation, recognizing and eliminating invading pathogens and viruses to maintain homeostasis. [7][8][9] The immune response to MTB antigens can be divided into two categories: innate immunity (also known as a nonspecific or natural immune response) and adaptive immunity (also known as an acquired or specific immune response). When the host is infected with MTB, the innate immune response and adaptive immune response collaborate to counteract the virulence of MTB.…”

Design and development of a multi‐epitope vaccine for the prevention of latent tuberculosis infection

“…Regarding the current status of anti-tuberculosis vaccine development, previous studies have demonstrated that traditional live attenuated vaccines, such as BCG, exhibit a protective efficacy ranging from 0 to 86% [11]. However, the progress of nucleic acid vaccines, including DNA vaccines, has been hindered since the research boom at the end of the last century, primarily due to the risk of genetic contamination [1].…”