Elisa Nemes

Elisa Nemes
University of Cape Town | UCT · South African Tuberculosis Vaccine Initiative (SATVI)

PhD

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144
Publications
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Publications

Publications (144)
Article
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We developed a flow cytometry‐based assay, termed D ifferential L eukocyte C ounting and I mmunophenotyping in C ryopreserved E x vivo whole blood (DLC‐ICE), that allows quantification of absolute counts and frequencies of leukocyte subsets and measures expression of activation, phenotypic and functional markers. We evaluated the performance of the...
Article
Introduction: The Bacille Calmette-Guérin (BCG) vaccine is usually administered at birth to protect against severe forms of tuberculosis in children. BCG also confers some protection against other infections, possibly mediated by innate immune training. We investigated whether newborn BCG vaccination modulates myeloid and natural killer (NK) cell...
Article
Full-text available
Tuberculosis (TB) remains a major public health problem and we lack a comprehensive understanding of how Mycobacterium tuberculosis (M. tb) infection impacts host immune responses. We compared the induced immune response to TB antigen, BCG and IL-1β stimulation between latently M. tb infected individuals (LTBI) and active TB patients. This revealed...
Article
Tuberculosis (TB) is a leading cause of global child mortality. Until the turn of the 21st century, Mycobacterium bovis bacille Calmette-Guerin (BCG) was the only vaccine to prevent TB. The pediatric TB vaccine pipeline has advanced in the past decade to include the evaluation of novel whole cell vaccines to replace infant BCG and investigation of...
Article
New tuberculosis vaccine candidates that are in the development pipeline need to be studied in people with HIV, who are at high risk of acquiring Mycobacterium tuberculosis infection and tuberculosis disease and tend to develop less robust vaccine-induced immune responses. To address the gaps in developing tuberculosis vaccines for people with HIV,...
Article
Immunization strategies against tuberculosis (TB) that confer better protection than neonatal vaccination with the 101-year-old Bacille Calmette-Guerin (BCG) are urgently needed to control the epidemic, but clinical development is hampered by a lack of established immune correlates of protection (CoPs). Two phase 2b clinical trials offer the first...
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Tuberculosis (TB) remains a leading infectious cause of death worldwide and the coronavirus disease 2019 pandemic has negatively impacted the global TB burden of disease indicators. If the targets of TB mortality and incidence reduction set by the international community are to be met, new more effective adult and adolescent TB vaccines are urgentl...
Article
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Background We evaluated the diagnostic and prognostic performance of a transcriptomic signature of tuberculosis (TB) risk (RISK11) and QuantiFERON-TB Gold-plus (QFTPlus) as combination biomarkers of TB risk. Methods Healthy South Africans who were HIV-negative aged 18–60 years with baseline RISK11 and QFTPlus results were evaluated in a prospectiv...
Preprint
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Many new TB vaccine candidates in the development pipeline need to be studied in people with HIV. People with HIV are at high risk of developing Mycobacterium tuberculosis (Mtb) infection and TB disease and tend to develop less robust vaccine induced immune responses. Many questions remain unanswered regarding priority vaccine indications, clinical...
Article
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Immune reconstitution inflammatory syndrome (IRIS) can be a complication of antiretroviral therapy (ART) in patients with advanced HIV, but its pathogenesis is uncertain. In tuberculosis (TB) endemic countries, IRIS is often associated with mycobacterial infections or Bacille‐Calmette‐Guerin (BCG) vaccination in children. With no predictive or conf...
Article
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Background Non-protein antigen classes can be presented to T cells by near-monomorphic antigen-presenting molecules such as CD1, MR1, and butyrophilin 3A1. Such T cells, referred to as donor unrestricted T (DURT) cells, typically express stereotypic T cell receptors. The near-unrestricted nature of DURT cell antigen recognition is of particular int...
Article
The rapid development of COVID-19 vaccines was the result of decades of research to establish flexible vaccine platforms and understand pathogens with pandemic potential, as well as several novel changes to the vaccine discovery and development processes that partnered industry and governments. And while vaccines offer the potential to drastically...
Article
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Reversion of immune sensitization tests for Mycobacterium tuberculosis (M.tb) infection, such as interferon-gamma release assays or tuberculin skin test, has been reported in multiple studies. We hypothesized that QuantiFERON-TB Gold (QFT) reversion is associated with a decline of M.tb-specific functional T cell responses, and a distinct pattern of...
Article
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The risk of tuberculosis (TB) disease is higher in individuals with recent Mycobacterium tuberculosis ( M.tb ) infection compared to individuals with more remote, established infection. We aimed to define blood-based biomarkers to distinguish between recent and remote infection, which would allow targeting of recently infected individuals for preve...
Preprint
Full-text available
Antigen classes other than proteins can be presented to T cells by near-monomorphic antigen-presenting molecules such as CD1, MR1, and butyrophilin 3A1. We sought to define the roles of donor unrestricted T (DURT) cells, including MR1-reactive MAIT cells, CD1b-reactive glucose monomycolate (GMM)-specific T cells, CD1d-reactive NKT cells, and γδ T c...
Article
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Background: Recent Mycobacterium tuberculosis (M.tb) infection is associated with a higher risk of progression to tuberculosis disease, compared to persistent infection after remote exposure. However, current immunodiagnostic tools fail to distinguish between recent and remote infection. We aimed to characterise the immunobiology associated with a...
Preprint
Full-text available
The risk of tuberculosis (TB) disease is higher in individuals with recent Mycobacterium tuberculosis ( M.tb ) infection compared to individuals with more remote, established infection. We aimed to define blood-based biomarkers to distinguish between recent and remote infection, which would allow targeting of recently infected individuals for preve...
Article
Full-text available
Rationale: Current diagnostic tests fail to identify individuals at higher risk of progression to tuberculosis disease, such as those with recent Mycobacterium tuberculosis infection, who should be prioritized for targeted preventive treatment. Objectives: To define a blood-based biomarker, measured with a simple flow cytometry assay, that can s...
Preprint
Full-text available
Tuberculosis (TB) remains a major public health problem with host-directed therapeutics offering potential as novel treatment strategies. However, their successful development still requires a comprehensive understanding of how Mycobacterium tuberculosis ( M.tb ) infection impacts immune responses. To address this challenge, we applied standardised...
Article
The efficacy of bacille Calmette-Guerin (BCG) vaccination against tuberculosis is highly variable, and protective immunity elicited by BCG is poorly understood. We compared the cytokine/chemokine profiles of peripheral blood mononuclear cells (PBMC) obtained from infants BCG-vaccinated at birth to those of PBMC obtained from infants before (delayed...
Preprint
Background Recent Mycobacterium tuberculosis (M.tb) infection is associated with a higher risk of progression to tuberculosis disease, compared to persistent infection after remote exposure. However, current immunodiagnostic tools fail to distinguish between recent and remote infection. We aimed to characterise the immunobiology associated with acq...
Article
Full-text available
Background Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) infection and is a major public health problem. Clinical challenges include the lack of a blood-based test for active disease. Current blood-based tests, such as QuantiFERON (QFT) do not distinguish active TB disease from asymptomatic Mtb infection. Methods We hypothesized...
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We characterize the breadth, function and phenotype of innate and adaptive cellular responses in a prevention of Mycobacterium tuberculosis infection trial. Responses are measured by whole blood intracellular cytokine staining at baseline and 70 days after vaccination with H4:IC31 (subunit vaccine containing Ag85B and TB10.4), Bacille Calmette-Guer...
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We characterize the breadth, function and phenotype of innate and adaptive cellular responses in a prevention of Mycobacterium tuberculosis infection trial. Responses are measured by whole blood intracellular cytokine staining at baseline and 70 days after vaccination with H4:IC31 (subunit vaccine containing Ag85B and TB10.4), Bacille Calmette-Guer...
Article
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MR1-restricted T (MR1T) cells are defined by their recognition of metabolite antigens presented by the monomorphic MHC class 1-related molecule, MR1, the most highly conserved MHC class I related molecule in mammalian species. Mucosal-associated invariant T (MAIT) cells are the predominant subset of MR1T cells expressing an invariant TCR α-chain, T...
Article
Significance Early-life immune responses have been described as suboptimal, with neonates and infants being susceptible to infections. Vγ9Vδ2 T cells are the first T lymphocytes to be generated in the human fetus. Their T cell receptor-mediated responses to in vitro stimulation and their effector functions at birth are weaker compared with those in...
Article
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Background Adolescents in the Western Cape Province of South Africa had high force of Mycobacterium tuberculosis (MTB) infection (14% per annum) and high TB incidence (710 per 100,000 person–years) in 2005. We describe subsequent temporal changes in adolescent TB disease notification rates for the decade 2005–2015. Method We conducted an analysis...
Article
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The current tuberculosis (TB) vaccine, Bacille Calmette-Guerin (BCG), is effective in preventing TB in young children but was developed without a basic understanding of human immunology. Most modern TB vaccine candidates have targeted CD4+ T cell responses, thought to be important for protection against TB disease, but not known to be sufficient or...
Preprint
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Background: Provision of tuberculosis preventive treatment (TPT) to individuals with Mycobacterium tuberculosis (M.tb) infection (TBI) is a key strategy to reduce the global tuberculosis burden. Tuberculosis risk is significantly higher after recent compared to remote TBI. We aimed to define a blood-based biomarker, measured with a simple flow cyto...
Article
Full-text available
The performance of host blood-based biomarkers for tuberculosis (TB) in HIV-infected patients on antiretroviral therapy (ART) has not been fully assessed. We evaluated the immune phenotype and functionality of antigen-specific T-cell responses in HIV positive (+) participants with TB (n = 12) compared to HIV negative (−) participants with either TB...
Preprint
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MR1-restricted T cells (MR1Ts) are a T cell subset that recognizes and mediate host immune responses to a broad array of microbial pathogens, including Mycobacterium tuberculosis . Here, we sought to characterize development of circulating human MR1T cells, defined by MR1-5-OP-RU tetramer labelling and expression of TRAV1-2/CD26/CD161. We analyzed...
Article
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Background: Early secretory antigenic target-6 (ESAT-6) is an immunodominant Mycobacterium tuberculosis (M.tb) antigen included in novel vaccines against tuberculosis (TB) and in interferon-gamma (IFN-γ) release assays (IGRAs). Therefore, the availability of an ESAT-6-free IGRA is essential to determine M.tb infection status following vaccination...
Article
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Tuberculosis (TB) is the leading cause of mortality from a single infectious agent, Mycobacterium tuberculosis Relevant immune targets of the partially efficacious TB vaccine bacille Calmette-Guérin (BCG) remain poorly defined. Mucosal-associated invariant T (MAIT) cells are MHC-related protein 1 (MR1)-restricted T cells, which are reactive against...
Article
Vaccine development against tuberculosis (TB) is based on the induction of adaptive immune responses endowed with long-term memory against mycobacterial antigens. Memory B and T cells initiate a rapid and robust immune response upon encounter with Mycobacterium tuberculosis, thus achieving long-lasting protection against infection. Recent studies h...
Article
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Background: The immune reconstitution inflammatory syndrome (IRIS) in HIV-infected infants and young children is relatively understudied in regions endemic for HIV and TB. We aimed to describe incidence, clinical features and risk factors of pediatric IRIS in Sub-Saharan Africa and India. Methods and findings: We conducted an observational multi...
Article
SETTING South Africa. OBJECTIVE 1) To measure changes in the adolescent prevalence of latent tuberculous infection (LTBI) between 2005 and 2015, and 2) to evaluate medium-term impact of TB control measures on LTBI prevalence. DESIGN We compared baseline data from a cohort study (2005-2007) and a vaccine trial (2014-2015) which enrolled adolescents...
Preprint
Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) infection and is a major public health problem with an estimated 1.7 billion persons infected worldwide. Clinical challenges in TB include the lack of a blood-based test for active disease, and the absence of prognostic biomarkers for early treatment response. Current blood based tests...
Article
Full-text available
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 pre-clinical 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...
Data
Pre-vaccination antigen-specific CD4 (A) and CD8 (B) T cell responses by individual antigens contained in each vaccine. Frequencies of antigen-specific, Th1-cytokine expressing CD4 or CD8 T cells pre-vaccination. Points denote sample trimmed means and error bars denote 95% CI. Solid error bar lines indicate responses that significantly exceeded 0.0...
Data
Cumulative axis predictivity of cytokine co-expression profiles for vaccine-induced memory CD4 T cells. Cumulative axis predictivity for k principal components represents the proportion of variation in the scaled vaccine-induced memory response for each cytokine combination captured by the first k principal components (see Materials and Methods for...
Data
Pair-wise comparisons of cytokine co-expression profiles for vaccine-induced memory CD4 T cell responses between vaccines. Cells display maximum Bayes factors calculated based on the p-values from hypothesis tests for a difference between vaccines in scaled vaccine-induced memory CD4 T cell responses for certain cytokine combinations in M.tb-uninfe...
Data
Effect of underlying M.tb infection status on vaccine-induced memory response profile for CD4 T cells for selected cytokine co-expression subsets. Differences between M.tb-infected and -uninfected individuals in scaled vaccine-induced frequencies of antigen-specific memory TNF+IL-2+, single IFNγ+, single IL-2+ and IFNγ+TNF+IL-2+ CD4 T cell response...
Data
Vaccine-induced IL-17+ memory CD4 (A) and CD8 (B) T cell responses by vaccine and M.tb infection status. Frequencies of antigen-specific IL17-expressing CD4 or CD8 responses at the final time point in each trial, relative to the pre-vaccination frequencies (i.e. memory response minus pre-vaccination response). Points denote sample trimmed means, an...
Data
Sample sizes by time point for each vaccine trial. (XLSX)
Data
Effect of underlying M.tb infection status on vaccine-induced memory CD4 T cell response magnitudes. Differences between M.tb-infected and -uninfected individuals in vaccine-induced frequencies of antigen-specific memory CD4 T cell responses to antigens in each vaccine candidate (antigen-specific Th1 cytokine positive CD4 T cells at final trial tim...
Data
Antigen-specific memory CD4 (A) and CD8 (B) T cell responses by individual antigens contained in each vaccine. Vaccine-induced frequencies of antigen-specific memory CD4 T cell responses to antigens in each vaccine candidate (antigen-specific Th1 cytokine positive CD4 T cells at final trial time point minus pre-vaccination time point). Points denot...
Data
Effect of underlying M.tb infection status on pre-vaccination CD4 T cell response magnitudes. Differences between M.tb-infected and -uninfected individuals in pre-vaccination frequencies of antigen-specific CD4 T cell responses to antigens in each vaccine candidate. Points denote sample trimmed means and error bars denote 95% CI. Solid error bar li...
Data
Pair-wise comparisons of vaccine-induced memory CD4 T cell responses between vaccines. Cells display maximum Bayes factors calculated based on the p-values from hypothesis tests for a difference between vaccines in vaccine-induced memory CD4 T cell responses (antigen-specific Th1 cytokine positive CD4 T cells at final trial time point minus pre-vac...
Article
Vaccination with the tuberculosis (TB) vaccine Bacillus Calmette–Guérin (BCG) into the lungs of Rhesus macaques induces specific, local immune responses that delay infection in some animals and completely prevent it in others while protecting against TB disease.
Article
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The spelling of author Qianting Yang was corrected; the affiliation of author Stephanus T. Malherbe was corrected; and graphs in Fig. 4b and c were corrected owing to reanalysis of the data into the correct timed intervals.
Preprint
Full-text available
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 c...
Article
Purpose of review: To outline the need for a new tuberculosis (TB) vaccine; challenges for induction of vaccine-mediated protection in HIV-infected persons; and recent advances in clinical development. Recent findings: HIV has a detrimental effect on T-cell function, polarization and differentiation of Mycobacterium tuberculosis (Mtb)-specific T...
Article
Full-text available
Most infections with Mycobacterium tuberculosis (Mtb) manifest as a clinically asymptomatic, contained state, known as latent tuberculosis infection, that affects approximately one-quarter of the global population1. Although fewer than one in ten individuals eventually progress to active disease2, tuberculosis is a leading cause of death from infec...
Article
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Background Recent Mycobacterium tuberculosis (M.tb) infection predisposes to tuberculosis disease, the leading global infectious disease killer. We tested safety andefficacy of H4:IC31® vaccination or Bacille Calmette-Guerin (BCG) revaccination for prevention of M.tb infection. Methods QuantiFERON-TB Gold In-tube (QFT) negative, HIV-uninfected, re...
Article
For the ICU physician, the failure to consider, diagnose, and treat tuberculosis (TB) results in increased morbidity and mortality, and poses risks to both patients and health care providers. At present, the diagnosis of TB depends on the detection of either mycobacteria or mycobacterial products from clinical specimens. Given the risks posed to bo...
Article
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Background Maintenance of long-lasting immunity is thought to depend on stem cell memory T cells (TSCM), which have superior self-renewing capacity, longevity and proliferative potential compared with central memory (TCM) or effector (TEFF) T cells. Our knowledge of TSCM derives primarily from studies of virus-specific CD8⁺ TSCM. We aimed to determ...
Article
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Conflict of interest: T.J. Scriba reports grants received from BMGF by University of Cape Town, during the conduct of the study.Conflict of interest: E. Nemes received grants from the Bill and Melinda Gates Foundation, during the conduct of the study.