Progress in tuberculosis vaccine development and host-directed therapies—a state of the art review

The problem of antimicrobial resistance (AMR) and the associated morbidity and mortality due to antibiotic resistant bacterial pathogens is not new. However, AMR has been increasing at an alarming rate with appearances of diseases caused by bacteria exhibiting resistance to not just one but multiple classes of antibiotics. The World Health Organization (WHO) supported by governments, health ministries and health agencies has formulated global action plans to combat the rise in AMR, supporting a number of proven initiatives such as antimicrobial stewardship, investments in development of new classes of antibiotics, and educational programs designed to eliminate inappropriate antibiotic use. Vaccines as tools to reduce AMR have historically been under-recognized, yet the positive effect in reducing AMR has been well established. For example Haemophilus influenzae type B (Hib) as well as Streptococcus pneumoniae (pneumococcal) conjugate vaccines have impressive track records in not only preventing life threatening diseases caused by these bacteria, but also reducing antibiotic use and AMR. This paper will describe the drivers of antibiotic use and subsequent development of AMR; it will make the case how existing vaccines are already participating in combatting AMR, describe future prospects for the role of new vaccines in development to reduce AMR, and highlight challenges associated with future vaccine development to combat AMR.

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“…Despite this, the shortcomings of BCG make the development of more modern vaccine approaches a priority. 13 , 71 …”

Section: Vaccines In Early Stages Of Development With Potential To Rementioning

confidence: 99%

The role of vaccines in fighting antimicrobial resistance (AMR)

Jansen

Anderson

2018

Human Vaccines & Immunotherapeutics

107

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“…The only licensed TB vaccine, bacillus Calmette-Guérin, has variable efficacy, protecting children from disseminated TB but offering little protection for pulmonary TB in young people and adults-which is the primary transmitted form of the disease (1). Hundreds of preclinical and a dozen clinical vaccine candidates have been proposed (2), almost all focused on eliciting cell-mediated immunity. The costly failure of the most advanced clinical candidate, MVA85A, in a phase IIb clinical trial (3) has led to a reevaluation of what may constitute protective immunity to TB.…”

mentioning

confidence: 99%

Latently and uninfected healthcare workers exposed to TB make protective antibodies against Mycobacterium tuberculosis

Wang

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

145

158

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The role of Igs in natural protection against infection by Mycobacterium tuberculosis (Mtb), the causative agent of TB, is controversial. Although passive immunization with mAbs generated against mycobacterial antigens has shown protective efficacy in murine models of infection, studies in B cell-depleted animals only showed modest phenotypes. We do not know if humans make protective antibody responses. Here, we investigated whether healthcare workers in a Beijing TB hospital-who, although exposed to suprainfectious doses of pathogenic Mtb, remain healthy-make antibody responses that are effective in protecting against infection by Mtb. We tested antibodies isolated from 48 healthcare workers and compared these with 12 patients with active TB. We found that antibodies from 7 of 48 healthcare workers but none from active TB patients showed moderate protection against Mtb in an aerosol mouse challenge model. Intriguingly, three of seven healthcare workers who made protective antibody responses had no evidence of prior TB infection by IFN-γ release assay. There was also good correlation between protection observed in vivo and neutralization of Mtb in an in vitro human whole-blood assay. Antibodies mediating protection were directed against the surface of Mtb and depended on both immune complexes and CD4+ T cells for efficacy. Our results indicate that certain individuals make protective antibodies against Mtb and challenge paradigms about the nature of an effective immune response to TB.TB | antibodies | immune complex | humoral immunity | TB restrictors

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“…Kaufmann et al [18] studied adjuvant Autologous MSC therapy in South African patients with MDR/XDR-TB is establishing the safety in patients with MDR/XDR TB in Durban, King Dinuzulu Hospital Complex and is investigating immunological mechanisms of anti-TB responses and markers of a response to therapy. Specific efforts have been made to study responses to MSC treatment defined by HR-CT imaging as well as to assess the best incremental value of this adjuvant therapy in the subset of patients who would benefit from this mode of cellular therapy, compared to other possible immune-interventions targeting the host immune response [18].…”

Section: Mesenchymal Stromal Cells (Mscs)mentioning

confidence: 99%

“…Specific efforts have been made to study responses to MSC treatment defined by HR-CT imaging as well as to assess the best incremental value of this adjuvant therapy in the subset of patients who would benefit from this mode of cellular therapy, compared to other possible immune-interventions targeting the host immune response [18].…”

Section: Mesenchymal Stromal Cells (Mscs)mentioning

confidence: 99%

Stem Cell Therapy: an Adjunct in the Treatment of MDR Tuberculosis

Khan

Zaidi

Thawani

2017

JSRT

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Tuberculosis is a global health issue and a major cause of death worldwide. Emerging infectious disease as multidrug resistance and extensively drug resistance tuberculosis triggers the importance to improve the current therapy or else develop an innovative approach. Currently stem cell transplantation emerged as new therapeutic to overcome tuberculosis. Recent studies provide an opportunity to explore stem cell in treatment of drug resistant tuberculosis. This review is in concern with the regime, future effect and challenges of stem cell therapy in drug resistant patients. Keywords:

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Progress in tuberculosis vaccine development and host-directed therapies—a state of the art review

Cited by 200 publications

References 199 publications

The role of vaccines in fighting antimicrobial resistance (AMR)

The role of vaccines in fighting antimicrobial resistance (AMR)

Latently and uninfected healthcare workers exposed to TB make protective antibodies against Mycobacterium tuberculosis

Stem Cell Therapy: an Adjunct in the Treatment of MDR Tuberculosis

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