Safety and immunogenicity of the novel tuberculosis vaccine ID93 + GLA-SE in BCG-vaccinated healthy adults in South Africa: a randomised, double-blind, placebo-controlled phase 1 trial

Penn-Nicholson, Adam; Tameris, Michèle; Smit, Erica; Day, Tracey; Musvosvi, Munyaradzi; Jayashankar, Lakshmi; Vergara, Julie; Mabwe, Simbarashe; Bilek, Nicole; Geldenhuys, Hendrik; Luabeya, Angelique Kany Kany; Ellis, Ruth D.; Ginsberg, Ann M.; Hanekom, Willem A.; Reed, Steven G.; Coler, Rhea N.; Scriba, Thomas J.; Hatherill, Mark

doi:10.1016/s2213-2600(18)30077-8

Cited by 125 publications

(95 citation statements)

References 29 publications

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“…Vaccine-induced CD4 T cell responses were higher than CD8 T cell responses. In addition, as expected and previously described [8- 15,21], these responses typically peaked at the measurement timepoint immediately after vaccine administration and waned thereafter. Inter-donor variability in CD4 T cell responses to M72/AS01E, H1:IC31…”

Section: Longitudinal Vaccine-induced T Cell Responsessupporting

confidence: 85%

“…Further, we did not include analyses of antigenspecific antibody responses, which may also be important in immunity against M.tb [27,28], largely because antibody responses were not measured in each trial assessed here. It should be noted that high-level antigen-specific IgG responses were induced by a number of these TB vaccine candidates [14,15] and we suggest that such responses should be measured in vaccine trials and included in future head-to-head comparisons.…”

Section: Discussionmentioning

confidence: 99%

“…To facilitate rational, data-driven decisions about vaccine candidate advancement, we compared Bacillus Calmette-Guérin (BCG) [8] and six novel TB vaccine candidates, including MVA85A [9,10], AERAS-402 [11], H1:IC31 [12], M72/AS01E [13,14], ID93+GLA-SE [15] and H56:IC31 [16], by their induced antigen-specific CD4 and CD8 T cell responses from data generated in human clinical trials previously completed at the South African TB Vaccine Initiative. The immune responses were measured using the same immunological assay [17,18], enabling direct comparisons between vaccines.…”

Section: Introductionmentioning

confidence: 99%

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A comparison of antigen-specific T cell responses induced by six novel tuberculosis vaccine candidates

Rodo

Rozot

Nemes

et al. 2018

Preprint

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Eradication of tuberculosis (TB), the world's leading cause of death due to infectious disease, requires a highly efficacious TB vaccine. Many TB vaccine candidates are in preclinical and clinical development but only a few can be advanced to large-scale efficacy trials due to limited global resources. We aimed to perform a statistically rigorous comparison of the antigen-specific T cell responses induced by six novel TB vaccine candidates and the only licensed TB vaccine, Bacillus Calmette-Guérin (BCG). We propose that the antigen-specific immune response induced by such vaccines provides an objective, data-driven basis for prioritisation of vaccine candidates for efficacy testing. We analyzed frequencies of antigen-specific CD4 and CD8 T cells expressing IFNγ, IL-2, TNF and/or IL-17 from adolescents or adults, with or without Mycobacterium tuberculosis (M.tb) infection, who received MVA85A, AERAS-402, H1:IC31, H56:IC31, M72/AS01E, ID93+GLA-SE or BCG. Two key response characteristics were analyzed, namely response magnitude and cytokine co-expression profile of the memory T cell response that persisted above the pre-vaccination response to the final study visit in each trial. All vaccines preferentially induced antigen-specific CD4 T cell responses expressing Th1 cytokines; levels of IL-17-expressing cells were low or not detected. In M.tb-uninfected and -infected individuals, M72/AS01E induced higher memory Th1 cytokine-expressing CD4 T cell responses than other novel vaccine candidates. Cytokine co-expression profiles of memory CD4 T cells induced by different novel vaccine candidates were alike. Our study suggests that the T cell response feature which most differentiated between the TB vaccine candidates was response magnitude, whilst functional profiles suggested a lack of response diversity. Since M72/AS01E induced the highest memory CD4 T cell response it demonstrated the best vaccine take. In the absence of immunological correlates of 3 protection the likelihood of finding a protective vaccine by empirical testing of candidates may be increased by the addition of candidates that induce distinct immune characteristics. Author summary Tuberculosis (TB) causes more deaths than any other single infectious disease, and a new, improved vaccine is needed to control the epidemic. Many new TB vaccine candidates are in clinical development, but only one or two can be advanced to expensive efficacy trials. In this study, we compared magnitude and functional attributes of memory T cell responses induced in recently conducted clinical trials by six TB vaccine candidates, as well as BCG. The results suggest that these vaccines induced CD4 and CD8 T cell responses with similar functional attributes, but that one vaccine, M72/AS01E, induced the largest responses. This finding may indicate a lack of diversity in T cell responses induced by different TB vaccine candidates. A repertoire of vaccine candidates that induces more diverse immune response characteristics may increase the chances of finding a protective vaccine a...

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Section: Longitudinal Vaccine-induced T Cell Responsessupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A comparison of antigen-specific T cell responses induced by six novel tuberculosis vaccine candidates

Rodo

Rozot

Nemes

et al. 2018

Preprint

Self Cite

View full text Add to dashboard Cite

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“…DAR-901 is being tested in a POI efficacy trial (NCT02712424) of a three-dose regimen among 650 IGRAnegative Tanzanian adolescents followed for IGRA conversion over 24 months. ID93 + GLA/SE is a polyprotein comprised of the four M. tuberculosis antigens Rv1813c, Rv2608, Rv3619c and Rv3620c, formulated with GLA-SE adjuvant, a synthetic tolllike receptor 4 agonist in a stable oil-in-water emulsion (Penn-Nicholson et al, 2018). ID93 + GLA/SE is being tested in a safety and immunogenicity trial (NCT03806686) of a three-dose regimen among 107 previously BCG-vaccinated, IGRA-negative Korean healthcare workers followed for 14 months for IGRA conversion.…”

Section: Pre-exposure Approaches To Prevention Of Infection (Poi) In mentioning

confidence: 99%

Clinical Development of New TB Vaccines: Recent Advances and Next Steps

2020

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Mycobacterium tuberculosis (Mtb) kills more people worldwide than any single infectious pathogen, yet the only vaccine licensed against tuberculosis, Bacille Calmette Guerin (BCG) is approaching its centenary. Two recent advances in clinical tuberculosis vaccine development have invigorated the field. BCG revaccination of interferon-gamma release assay (IGRA) negative adolescents provided 45% protection against sustained Mtb infection defined by IGRA conversion; and the protein-subunit vaccine M72/AS01 E provided 50% protection against progression from Mtb infection to tuberculosis disease in IGRA-positive adults. These findings provide encouraging evidence for pre-exposure and post-exposure approaches to vaccination against tuberculosis, both of which may be necessary to rapidly interrupt the cycle of Mtb transmission and sustain long-term impact on global tuberculosis control. New trials are needed to demonstrate efficacy of M72/AS01 E with greater precision, in a wider age range, in diverse epidemic settings, and in populations that include Mtb-uninfected and HIV-infected persons. Modeling the impact of mass campaigns with M72/AS01 E and other fast-follower vaccine candidates will be crucial to make the use case and demonstrate public health value for TB endemic countries. The size and scope of the next generation of efficacy trials, and the need to expand and accelerate the existing clinical development pipeline, will require public and private consortium funding and concerted political will.

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“…The main candidate subunit vaccines are M72/ASO1E [233] and H56:IC31 [176], previously mentioned, in addition to ID93:GLA-SE [236]. The latter is a fusion of four M. tuberculosis antigens (Rv1813, Rv2608, Rv3619 and Rv3620) [236] combined with the TLR-4 agonist adjuvant GLA-SE [237], which has completed a phase 2a trial successfully [238].…”

Section: Subunit Vaccinesmentioning

confidence: 99%

Towards new TB vaccines

Brazier

McShane

2020

Semin Immunopathol

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Mycobacterium tuberculosis remains the leading cause of death attributed to a single infectious organism. Bacillus Calmette-Guerin (BCG), the standard vaccine against M. tuberculosis, is thought to prevent only 5% of all vaccine-preventable deaths due to tuberculosis, thus an alternative vaccine is required. One of the principal barriers to vaccine development against M. tuberculosis is the complexity of the immune response to infection, with uncertainty as to what constitutes an immunological correlate of protection. In this paper, we seek to give an overview of the immunology of M. tuberculosis infection, and by doing so, investigate possible targets of vaccine development. This encompasses the innate, adaptive, mucosal and humoral immune systems. Though MVA85A did not improve protection compared with BCG alone in a large-scale clinical trial, the correlates of protection this has revealed, in addition to promising results from candidate such as VPM1002, M72/ASO1E and H56:IC31 point to a brighter future in the field of TB vaccine development.

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Safety and immunogenicity of the novel tuberculosis vaccine ID93 + GLA-SE in BCG-vaccinated healthy adults in South Africa: a randomised, double-blind, placebo-controlled phase 1 trial

Cited by 125 publications

References 29 publications

A comparison of antigen-specific T cell responses induced by six novel tuberculosis vaccine candidates

A comparison of antigen-specific T cell responses induced by six novel tuberculosis vaccine candidates

Clinical Development of New TB Vaccines: Recent Advances and Next Steps

Towards new TB vaccines

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