A5009129390- Tuberculosis Research and Epidemiology
- Monoclonal and Polyclonal Antibodies Research
- Mycobacterium research and diagnosis
- Chronic Lymphocytic Leukemia Research
- Immune Cell Function and Interaction
- Immunodeficiency and Autoimmune Disorders
- HIV Research and Treatment
- vaccines and immunoinformatics approaches
- Bacteriophages and microbial interactions
- Immunotherapy and Immune Responses
- Biosimilars and Bioanalytical Methods
- Glycosylation and Glycoproteins Research
- T-cell and B-cell Immunology
- Galectins and Cancer Biology
Ragon Institute of MGH, MIT and Harvard
2016-2025
University of Pittsburgh
2025
Harvard University
2020-2024
New York University
2015-2016
Exposure to Mycobacterium tuberculosis (Mtb) results in heterogeneous clinical outcomes including primary progressive and latent Mtb infection (LTBI). is identified using the tuberculin skin test interferon-γ (IFN-γ) release assay IGRA, a positive result may prompt chemoprophylaxis prevent progression tuberculosis. In present study, we report on cohort of Ugandan individuals who were household contacts patients with TB. These highly exposed but tested negative by IFN-γ test, ‘resisting’...
Abstract Background Mycobacterium tuberculosis remains a global health problem and clinical management is complicated by difficulty in discriminating between latent infection active disease. While M. tuberculosis-reactive antibody levels are heterogeneous, studies suggest that of IgG glycosylation differ disease states. Here we extend this observation across domains specificities to define changes with the greatest resolving power. Methods Capillary electrophoretic glycan analysis was...
Abstract Mycobacterium tuberculosis commonly causes persistent or chronic infection, despite the development of Ag-specific CD4 T cell responses. We hypothesized that M. evades elimination by responses manipulating MHC class II Ag presentation and activation tested this hypothesis comparing Ag85B-specific to bovis bacillus Calmette–Guérin (BCG) Pasteur in vivo vitro. found that, although persists lungs immunocompetent mice, BCG is cleared, clearance dependent. further discovered...
With an estimated 25% of the global population infected with Mycobacterium tuberculosis ( Mtb ), (TB) remains a leading cause death by infectious diseases. Humoral immunity following TB treatment is largely uncharacterized, and antibody profiling could provide insights into disease resolution. Here we focused on distinctive TB-specific serum features in active (ATB) compared them latent infection (LTBI) or treated ATB (txATB). As expected, di-galactosylated glycan structures (lacking sialic...
While control of Mycobacterium tuberculosis (Mtb) infection is generally understood to require Th1 cells and IFNγ, produces a spectrum immunological pathological phenotypes in diverse human populations. By characterizing Mtb mouse strains that model the genetic heterogeneity an outbred population, we identified comparably standard IFNγ-dependent but with substantially lower lung IFNγ levels. We report these mice have significantly altered CD4 T cell profile specifically lacks terminal...
Mounting evidence indicates that antibodies can contribute towards control of tuberculosis (TB). However, the underlying mechanisms humoral immune protection and whether be exploited in therapeutic strategies to combat TB are relatively understudied. Here we engineered receptor-binding Fc (fragment crystallizable) region an antibody recognizing Mycobacterium (Mtb) capsule, define Fc-mediated mechanism(s) Mtb restriction. We generated 52 variants either promote or inhibit specific effector...
South Africa has the highest prevalence of HIV and tuberculosis (TB) co-infection globally. Recurrent TB, caused by relapse or reinfection, makes up majority TB cases in Africa, infected individuals have a greater likelihood developing recurrent TB. Given that remains leading cause death for individuals, correlates recurrence protection/risk yet to be defined, here we sought understand antibody associated mechanisms investigating humoral response longitudinal cohort co-infected previously...
ABSTRACT Novel vaccination and therapeutic strategies are urgently needed to mitigate the tuberculosis (TB) epidemic. While extensive efforts have focused on potentiating cell-mediated immunity control Mycobacterium ( Mtb ) infection, less effort has been invested in exploiting humoral immune system combat . Emerging data point a role for antibodies microbial of , however precise mechanism(s) this remain incompletely understood. Here we took an antibody Fc-engineering approach determine...
In the version of this article originally published, there was an error in abstract. The word disease should not have been included sentence “These individuals were highly exposed to Mtb but tested negative by IFN-γ release assay and tuberculin skin test, ‘resisting’ development classic LTBI”. LTBI.” has corrected HTML PDF versions article.
Abstract Mycobacterium tuberculosis (Mtb), the causative agent of (TB), is a leading cause death by an infectious disease globally, with no efficacious vaccine. Antibodies are implicated in Mtb control, but mechanisms antibody action remain poorly understood. We assembled library TB monoclonal antibodies (mAb) and screened for ability to restrict mice, identifying protective targeting known novel antigens. To dissect mechanism mAb-mediated restriction, we optimized lipoarabinomannan-specific...