First-in-human trial of the post-exposure tuberculosis vaccine H56:IC31 in Mycobacterium tuberculosis infected and non-infected healthy adults

Luabeya, Angelique Kany Kany; Kagina, Benjamin M.; Tameris, Michèle; Geldenhuys, Hennie; Hoff, Søren T.; Shi, Zhongkai; Kromann, Ingrid; Hatherill, Mark; Mahomed, Hassan; Hanekom, Willem A.; Andersen, Peter Henrik; Scriba, Thomas J.; Schoeman, Elisma; Krohn, Colleen; Day, Cheryl L.; Africa, Hadn; Makhethe, Lebohang; Smit, Erica; Brown, Yolande; Suliman, Sara; Hughes, Elizabeth J.; Bang, Peter Fibiger; Snowden, Margaret Ann; McClain, Bruce; Hussey, Gregory

doi:10.1016/j.vaccine.2015.06.051

Cited by 170 publications

(142 citation statements)

References 43 publications

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“…The protection conferred by the vaccine appears to vary substantially between populations, and decline over time [62], However, the protection provided against adult-type disease is variable and its impact on epidemic transmission is minimal. Newer post-exposure vaccines are in development, but no protective efficacy has yet been established [63].…”

Section: Immunizationmentioning

confidence: 99%

“…Each of its three pillars applies to MDR/XDR-TB prevention, including the importance of intensified research and innovation (Table 3). Research priorities include the development of a strong evidence base for the optimal use of preventive therapy in high-risk populations, determining the protective efficacy of novel vaccines [63], developing sensitive and rapid diagnostic tests for DR-TB (directly from sputum samples), identifying biomarkers to predict future disease risk, identifying pragmatic methods to enhance case detection, testing new models of care to reduce time to effective treatment, developing treatment regimens that are short, safe and durable and improving infection control in all high transmission settings [65].…”

Section: Future Directions and Research Prioritiesmentioning

confidence: 99%

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Preventing the spread of multidrug-resistant tuberculosis and protecting contacts of infectious cases

Fox

Schaaf

Mandalakas

et al. 2017

Clinical Microbiology and Infection

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192 words Word count: 2,928References: 65 in main text, 77 including tables. Conflicts of interest:None to declare 2 Abstract Prevention of multidrug (MDR) and extensively drug-resistant tuberculosis (XDR-TB) is a top priority for global TB control, given the need to limit epidemic spread and considering the high cost, toxicity and poor treatment outcomes with available therapies. We performed a systematic literature review to evaluate the evidence for strategies to reduce MDR/XDR-TB transmission and disease progression.Rapid detection and timely initiation of effective treatment is critical to rendering MDR/XDR-TB cases non-infectious. The scale-up of rapid molecular testing has transformed the capacity of high-incidence settings to identify and treat MDR/XDR-TB patients. Optimised infection control measures in hospitals and clinics are critical to protect other patients and healthcare workers, while creative measures to reduce transmission within community hotspots require consideration. Targeted screening of high-risk communities may enhance early case-detection and limit the spread of MDR/XDR-TB. Among infected contacts, preventive therapy promises to reduce the risk of disease progression. This is supported by observational cohort studies, but randomised trials are urgently needed to confirm these observations and guide policy formulation.Substantial investment in MDR/XDR-TB prevention and care will be critical if the ambitious global goal of TB elimination is to be realised.3

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Section: Immunizationmentioning

confidence: 99%

Section: Future Directions and Research Prioritiesmentioning

confidence: 99%

Preventing the spread of multidrug-resistant tuberculosis and protecting contacts of infectious cases

Fox

Schaaf

Mandalakas

et al. 2017

Clinical Microbiology and Infection

View full text Add to dashboard Cite

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“…Administration of additional doses of BCG did not boost the protection afforded by BCG (8). Candidate vaccines against M. tuberculosis have focused largely on targeting immunodominant antigens that are secreted proteins, including Ag85A (9-12), Ag85B (12)(13)(14)(15)(16)(17), 16), TB10.4 (9,13,17), Rv1196, and Rv0125 (18,19). Enhanced protection over BCG has proven to be difficult to achieve, and safety issues and adverse events have caused concern (12,20).…”

mentioning

confidence: 99%

Identification of Mycobacterial RplJ/L10 and RpsA/S1 Proteins as Novel Targets for CD4⁺T Cells

et al. 2017

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Tuberculosis (TB) due to Mycobacterium tuberculosis remains a major global infectious disease problem, and a more efficacious vaccine is urgently needed for the control and prevention of disease caused by this organism. We previously reported that a genetically modified strain of Mycobacterium smegmatis called IKEPLUS is a promising TB vaccine candidate. Since protective immunity induced by IKEPLUS is dependent on antigen-specific CD4 ϩ T cell memory, we hypothesized that the specificity of the CD4 ϩ T cell response was a critical feature of this protection. Using in vitro assays of interferon gamma production (enzyme-linked immunosorbent spot [ELISPOT] assays) by splenocytes from IKEPLUS-immunized C57BL/6J mice, we identified an immunogenic peptide within the mycobacterial ribosomal large subunit protein RplJ, encoded by the Rv0651 gene. In a complementary approach, we generated major histocompatibility complex (MHC) class II-restricted T cell hybridomas from IKEPLUS-immunized mice. Screening of these T cell hybridomas against IKE-PLUS and ribosomes enriched from IKEPLUS suggested that the CD4 ϩ T cell response in IKEPLUS-immunized mice was dominated by the recognition of multiple components of the mycobacterial ribosome. Importantly, CD4 ϩ T cells specific for mycobacterial ribosomes accumulate to significant levels in the lungs of IKEPLUSimmunized mice following aerosol challenge with virulent M. tuberculosis, consistent with a role for these T cells in protective host immunity in TB. The identification of CD4 ϩ T cell responses to defined ribosomal protein epitopes expands the range of antigenic targets for adaptive immune responses to M. tuberculosis and may help to inform the design of more effective vaccines against tuberculosis.

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“…[369] Based on the reviewing of the reports, multistage synthetic recombinant proteins such as fusion protein ESAT-6, CFP-10, HspX, and a constant part of immunoglobulin G can promote the effective promoted immunity response in animals and humans during animal-laboratory studies and clinical trials. [34567101112]…”

mentioning

confidence: 99%

The Fusion Multistage Synthetic Peptides as the Best Candidates for New Tuberculosis Vaccine

Keikha¹,

Moghim²,

Fazeli³

et al. 2018

Adv Biomed Res

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First-in-human trial of the post-exposure tuberculosis vaccine H56:IC31 in Mycobacterium tuberculosis infected and non-infected healthy adults

Cited by 170 publications

References 43 publications

Preventing the spread of multidrug-resistant tuberculosis and protecting contacts of infectious cases

Preventing the spread of multidrug-resistant tuberculosis and protecting contacts of infectious cases

Identification of Mycobacterial RplJ/L10 and RpsA/S1 Proteins as Novel Targets for CD4⁺T Cells

The Fusion Multistage Synthetic Peptides as the Best Candidates for New Tuberculosis Vaccine

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First-in-human trial of the post-exposure tuberculosis vaccine H56:IC31 in Mycobacterium tuberculosis infected and non-infected healthy adults

Cited by 170 publications

References 43 publications

Preventing the spread of multidrug-resistant tuberculosis and protecting contacts of infectious cases

Preventing the spread of multidrug-resistant tuberculosis and protecting contacts of infectious cases

Identification of Mycobacterial RplJ/L10 and RpsA/S1 Proteins as Novel Targets for CD4+T Cells

The Fusion Multistage Synthetic Peptides as the Best Candidates for New Tuberculosis Vaccine

Contact Info

Product

Resources

About

Identification of Mycobacterial RplJ/L10 and RpsA/S1 Proteins as Novel Targets for CD4⁺T Cells