A5036323567- SARS-CoV-2 and COVID-19 Research
- Tuberculosis Research and Epidemiology
- COVID-19 Clinical Research Studies
- HIV Research and Treatment
- Immune Cell Function and Interaction
- Mycobacterium research and diagnosis
- T-cell and B-cell Immunology
- vaccines and immunoinformatics approaches
- Infectious Diseases and Tuberculosis
- Immunodeficiency and Autoimmune Disorders
- Pericarditis and Cardiac Tamponade
- COVID-19 epidemiological studies
- Long-Term Effects of COVID-19
- Immunotherapy and Immune Responses
- Pneumocystis jirovecii pneumonia detection and treatment
- Diagnosis and treatment of tuberculosis
- SARS-CoV-2 detection and testing
- HIV/AIDS Research and Interventions
- Cell death mechanisms and regulation
- Immune Response and Inflammation
- Cytomegalovirus and herpesvirus research
- Health, Environment, Cognitive Aging
- Genetic Associations and Epidemiology
- Chronic Lymphocytic Leukemia Research
- HIV/AIDS drug development and treatment
Wellcome Centre for Infectious Diseases Research in Africa
2018-2025
University of Cape Town
2016-2025
South African Radio Astronomy Observatory
2021-2023
Africa University
2019-2021
Inserm
1998-2015
Unité de Modélisation Mathématique et Informatique des Systèmes Complexes
2015
Cancéropôle Grand Ouest
2015
National Health Laboratory Service
2009-2014
Université de Montréal
2006-2013
Centre Hospitalier de l’Université de Montréal
2006-2013
Abstract The SARS-CoV-2 Omicron variant (B.1.1.529) has multiple spike protein mutations 1,2 that contribute to viral escape from antibody neutralization 3–6 and reduce vaccine protection infection 7,8 . extent which other components of the adaptive response such as T cells may still target severe outcomes is unknown. Here we assessed ability react in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, unvaccinated convalescent COVID-19 patients ( n = 70). Between 70% 80% CD4 +...
T cells are involved in control of coronavirus disease 2019 (COVID-19), but limited knowledge is available on the relationship between antigen-specific cell response and severity. Here, we used flow cytometry to assess magnitude, function, phenotype SARS 2–specific (SARS-CoV-2–specific) CD4+ 95 hospitalized COVID-19 patients, 38 them being HIV-1 and/or tuberculosis (TB) coinfected, non–COVID-19 patients. We showed that SARS-CoV-2–specific attributes, rather than were associated with...
SARS-CoV-2 variants that escape neutralization and potentially affect vaccine efficacy have emerged. T cell responses play a role in protection from reinfection severe disease, but the potential for spike mutations to immunity is incompletely understood. We assessed neutralizing antibody 44 South African COVID-19 patients either infected with Beta variant (dominant November 2020 May 2021) or before its emergence (first wave, Wuhan strain) provide an overall measure of immune evasion. show...
Ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has given rise to recombinant Omicron lineages that dominate globally (XBB.1), as well the emergence of hypermutated variants (BA.2.86). In this context, durable and cross-reactive T cell immune memory is critical for continued protection against COVID-19. We examined responses SARS-CoV-2 approximately 1.5 years since first emerged. describe sustained CD4+ CD8+ spike-specific in healthcare workers South Africa (n...
The molecular events involved in the establishment and maintenance of CD4+ central memory effector T cells (TCM TEM, respectively) are poorly understood. In this study, we demonstrate that ex vivo isolated TCM more resistant to both spontaneous Fas-induced apoptosis than TEM have an increased capacity proliferate persist vitro. Using global gene expression profiling, single cell proteomics, functional assays, show survival depends, at least part, on activation phosphorylation signal...
HIV-1 accumulates mutations in and around reactive epitopes to escape recognition killing by CD8+ T cells. Measurements of time should therefore provide information on which parameters are most important for cell–mediated vivo control HIV-1. Primary HIV-1–specific cell responses were fully mapped 17 individuals, the virus escape, ranged from days years, was measured each epitope. While higher magnitude an individual response associated with more rapid significant measure its relative...
Host resistance to Mycobacterium tuberculosis (Mtb) infection requires the activities of multiple leukocyte subsets, yet roles different innate effector cells during are incompletely understood. Here we uncover an unexpected association between eosinophils and Mtb infection. In humans, decreased in blood but enriched resected human lung lesions autopsy granulomas. An influx is also evident infected zebrafish, mice, nonhuman primate granulomas, where they functionally activated degranulate....
Summary The SARS-CoV-2 Omicron variant has multiple Spike (S) protein mutations that contribute to escape from the neutralizing antibody responses, and reducing vaccine protection infection. extent which other components of adaptive response such as T cells may still target severe outcomes is unknown. We assessed ability react with spike in participants who were vaccinated Ad26.CoV2.S or BNT162b2, unvaccinated convalescent COVID-19 patients (n = 70). found 70-80% CD4 CD8 cell was maintained...
Cellular necrosis during Mycobacterium tuberculosis (Mtb) infection promotes both immunopathology and bacterial dissemination. Glutathione peroxidase-4 (Gpx4) is an enzyme that plays a critical role in preventing iron-dependent lipid peroxidation–mediated cell death (ferroptosis), process previously implicated the necrotic pathology seen Mtb-infected mice. Here, we document altered GPX4 expression, glutathione levels, peroxidation patients with active assess of this pathway mice genetically...
Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposures, from infection or vaccination, can potently boost spike antibody responses. Less is known about the impact of repeated exposures on T cell Here, we compare prevalence and frequency peripheral SARS-CoV-2-specific immunoglobulin G (IgG) responses in 190 individuals with complex SARS-CoV-2 exposure histories. As expected, an increasing number significantly enhances magnitude IgG responses, while improve responders...
Few studies from Africa have described the clinical impact of co-infections on SARS-CoV-2 infection. Here, we investigate presentation and outcome infection in an African setting high HIV-1 tuberculosis prevalence by observational case cohort patients. A comparator group non participants is included. The study includes 104 adults with whom 29.8% are co-infected. Two or more co-morbidities present 57.7% participants, including (30%) active (14%). Amongst patients dually infected SARS-CoV-2,...
Abstract SARS-CoV-2 clearance requires adaptive immunity but the contribution of neutralizing antibodies and T cells in different immune states is unclear. Here we ask which responses associate with long-term infection HIV-mediated immunosuppression after suppressive antiretroviral therapy (ART) initiation. We assembled a cohort infected people South Africa ( n = 994) including participants advanced HIV disease characterized by due to cell depletion. Fifty-four percent had prolonged (>1...
Background Sputum Mycobacterium tuberculosis (Mtb) culture is commonly used to assess response antibiotic treatment in individuals with pulmonary (TB). Such techniques are constrained by the slow growth rate of Mtb, and more sensitive methods monitor Mtb clearance needed. The goal this study was evaluate changes plasma cytokines patients undergoing for TB as a means identifying candidate host markers associated microbiologic therapy. Methods Twenty-four cytokines/chemokines were measured 42...
Abstract Chronic activation of T cells is a hallmark HIV-1 infection and plays an important role in disease progression. We previously showed that the engagement inhibitory receptor programmed death (PD)-1 on HIV-1–specific CD4+ CD8+ leads to their functional exhaustion vitro. However, little known about impact PD-1 expression turnover maturation status during course disease. In this study, we show upregulated all cell subsets, including naive, central memory, transitional memory...
Several immune-based assays have been suggested to differentiate latent from active tuberculosis. However, their relative performance as well efficacy in HIV-infected persons, a highly at-risk population, remains unclear. In study of 81 individuals, divided into four groups based on HIV-1 status and TB disease activity, we compared the differentiation (CD27, KLRG1), activation (HLA-DR), homing potential (CCR4, CCR6, CXCR3, CD161) functional profiles (IFNγ, IL-2 TNFα) Mycobacterium...
Understanding early immunological events during HIV-1 infection that may set the course of disease progression is important for identifying correlates viral control. This study explores association differentiation profiles HIV-specific and total memory CD8(+) T cells with point. A cohort 47 HIV-1-infected individuals, differing points at 12 mo, were recruited acute infection. We identified magnitude IFN-gamma(+) cell responses 6 mo postinfection did not associate point mo. subset 16...
The diagnosis of pulmonary tuberculosis in HIV-infected individuals is particularly 33 challenging, as HIV-induced alterations the immune system lead to reduced cavitations, 34 limiting sensitivity sputum-based assays (1).Thus, alternate markers are needed 35 distinguish between latent (LTBI) and active TB (aTB) this high-risk group.Several 36 attributes Mtb-specific CD4+ T cells have been shown efficiently delineate LTBI 37 aTB HIV-uninfected individuals, including their polyfunctional or...
Recent data from mice and non-human primate models of tuberculosis suggested that CD153, a TNF super family member, plays an important role in Mycobacterium (Mtb) control. However, this molecule has not been comprehensively evaluated humans. Here, we show the proportion Mtb-specific CD4 T cells expressing CD153 was significantly reduced active TB patients compared to latently infected persons. Importantly, CD153+ response inversely correlated with lung bacterial load, inferred by Xpert cycle...
The development of non-sputum-based assays for tuberculosis (TB) diagnosis and treatment monitoring is a key priority. Recent data indicate that whole blood-based to assess the phenotype Mycobacterium (Mtb)-specific CD4 T cells hold promise this purpose require further investigation in well-characterised TB cohorts. In study, we investigated relationship between phenotypic signature Mtb-specific responses, disease extent response.Using flow cytometry, measured expression functional markers...