The status of tuberculosis vaccine development

Schrager, Lewis K.; Vekemens, Johan; Drager, Nick; Lewinsohn, David; Olesen, Ole F.

doi:10.1016/s1473-3099(19)30625-5

Cited by 143 publications

(118 citation statements)

References 86 publications

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“…BCG vaccination is associated with a 30% reduction in mortality rate by pathogens especially in developing countries [23] and 50% reduction in mortality related to pneumonia [24]. The favourable non-specific effects of the BCG vaccine persist for a time after the neonatal period up to 10 years [25]. Trained immunity is referred to innate immune system that could display memory characteristics, after spiked by pathogens or certain live attenuated vaccines (''training effect"), not only toward the same infectious agents but also non-specifically against different pathogens (cross-protection).…”

Section: Vaccine Age and Gender Relation To Covid-19 Infectionmentioning

confidence: 99%

Bacillus Calmette–Guérin vaccine, antimalarial, age and gender relation to COVID-19 spread and mortality

El-Gendy

Saeed

Ali

et al. 2020

Vaccine

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Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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Section: Vaccine Age and Gender Relation To Covid-19 Infectionmentioning

confidence: 99%

Bacillus Calmette–Guérin vaccine, antimalarial, age and gender relation to COVID-19 spread and mortality

El-Gendy

Saeed

Ali

et al. 2020

Vaccine

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“…However, to achieve this goal, many hurdles remain to be overcome. A major hindrance is the lack of a known immune correlate of protection in animals and humans [116]. As evidenced by many clinical and preclinical studies, robust immunogenicity does not always translate to improved protective efficacy [26,35,102].…”

Section: Discussionmentioning

confidence: 99%

“…Another hurdle is the lack of an animal model that faithfully recapitulates the spectrum of human TB disease including latent TB infection (LTBI) [117]. Interest for developing a controlled human infection model of TB is increasing as a more reliable assessment of vaccines' efficacy at an early stage of development [116][117][118].…”

Section: Discussionmentioning

confidence: 99%

Preclinical Progress of Subunit and Live Attenuated Mycobacterium tuberculosis Vaccines: A Review following the First in Human Efficacy Trial

Watt

Liu

2020

Pharmaceutics

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Tuberculosis (TB) is the global leading cause of death from an infectious agent with approximately 10 million new cases of TB and 1.45 million deaths in 2018. Bacille Calmette-Guérin (BCG) remains the only approved vaccine for Mycobacterium tuberculosis (M. tb, causative agent of TB), however clinical studies have shown BCG has variable effectiveness ranging from 0–80% in adults. With 1.7 billion people latently infected, it is becoming clear that vaccine regimens aimed at both post-exposure and pre-exposure to M. tb will be crucial to end the TB epidemic. The two main strategies to improve or replace BCG are subunit and live attenuated vaccines. However, following the failure of the MVA85A phase IIb trial in 2013, more varied and innovative approaches are being developed. These include recombinant BCG strains, genetically attenuated M. tb and naturally attenuated mycobacteria strains, novel methods of immunogenic antigen discovery including for hypervirulent M. tb strains, improved antigen recognition and delivery strategies, and broader selection of viral vectors. This article reviews preclinical vaccine work in the last 5 years with focus on those tested against M. tb challenge in relevant animal models.

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“…There are currently over 20 vaccines in pre-clinical and clinical studies, and these can be classified into three groups: live-attenuated, inactivated whole cell and subunit vaccines [83] . For subunit vaccines, either an adjuvant or a viral vector is required to achieve sufficient immune stimulation [84] . A century later after the development of BCG, all new TB vaccines have to undergo a highly regulated process which includes preclinical testing in animal models, phase I trials in small groups of healthy adults, phase II trials with expanding numbers and clinical characteristics of individuals and, finally, phase III trials with large number of individuals in multiple geographic locations.…”

Section: Examples Of New Subunit Viral Vector and Whole Cell Tb Vaccmentioning

confidence: 99%

Bacille Calmette Guérin (BCG) and new TB vaccines: Specific, cross-mycobacterial and off-target effects

Fritschi

Curtis

Ritz

2020

Paediatric Respiratory Reviews

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The Bacille Calmette Guérin (BCG) vaccine was developed over a century ago and has become one of the most used vaccines without undergoing a modern vaccine development life cycle. Despite this, the vaccine has protected many millions from severe and disseminated forms of tuberculosis (TB). In addition, BCG has cross-mycobacterial effects against non-tuberculous mycobacteria and off-target (also called non-specific or heterologous) effects against other infections and diseases. More recently, BCG’s effects on innate immunity suggest it might improve the immune response against viral respiratory infections including SARS-CoV-2. New TB vaccines, developed over the last 30 years, show promise, particularly in prevention of progression to disease from TB infection in young adults. The role of BCG in the context of new TB vaccines remains uncertain as most participants included in trials have been previously BCG immunised. BCG replacement vaccines are in efficacy trials and these may also have off-target effects.

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The status of tuberculosis vaccine development

Cited by 143 publications

References 86 publications

Bacillus Calmette–Guérin vaccine, antimalarial, age and gender relation to COVID-19 spread and mortality

Bacillus Calmette–Guérin vaccine, antimalarial, age and gender relation to COVID-19 spread and mortality

Preclinical Progress of Subunit and Live Attenuated Mycobacterium tuberculosis Vaccines: A Review following the First in Human Efficacy Trial

Bacille Calmette Guérin (BCG) and new TB vaccines: Specific, cross-mycobacterial and off-target effects

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