A5102888782- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Immune responses and vaccinations
- Immunodeficiency and Autoimmune Disorders
- Immune Response and Inflammation
- Diagnosis and treatment of tuberculosis
- vaccines and immunoinformatics approaches
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Fungal Infections and Studies
- Immune cells in cancer
- interferon and immune responses
- T-cell and B-cell Immunology
- Pneumonia and Respiratory Infections
- Peptidase Inhibition and Analysis
- Pediatric health and respiratory diseases
- Clostridium difficile and Clostridium perfringens research
- Cytokine Signaling Pathways and Interactions
- RNA and protein synthesis mechanisms
- Antifungal resistance and susceptibility
- Advanced Glycation End Products research
- Biochemical and Molecular Research
- Heme Oxygenase-1 and Carbon Monoxide
- Phagocytosis and Immune Regulation
- Escherichia coli research studies
Centenary Institute
2021-2024
The University of Sydney
2021-2024
Royal Prince Alfred Hospital
2022-2024
Colorado State University
2012-2021
University of Maryland, College Park
2008
Corixa Corporation
2006
Midwestern University
2002-2004
University of New Mexico
1997-1999
The University of Texas Southwestern Medical Center
1997
Trudeau Institute
1992-1993
Abstract Complexing TLR9 agonists such as plasmid DNA to cationic liposomes markedly potentiates their ability activate innate immunity. We therefore reasoned that complexed with or other TLR could be used effective vaccine adjuvants. To test this hypothesis, the adjuvant effects of were assessed in mice. found nucleic acids (liposome-Ag-nucleic acid complexes; LANAC) particularly adjuvants for eliciting CD4+ and CD8+ T cell responses against peptide protein Ags. Notably, LANAC containing...
Background Mycobacterium tuberculosis (Mtb), the causative agent of (TB), is a facultative intracellular pathogen that can persist within host. The bacteria are thought to be in state reduced replication and metabolism as part chronic lung infection. Many vitro studies have dissected hypothesized environment infected lung, defining bacterial response pH, starvation hypoxia. While these experiments afforded great insight, picture remains incomplete. only way study combined effects...
Abstract Mice lacking expression of granulocyte macrophage-colony stimulating factor (GM-CSF KO) are unable to contain Mycobacterium tuberculosis (M. tuberculosis) growth and succumb infection by 35 days following pulmonary challenge. GM-CSF KO mice do not express normal levels the inflammatory cytokine tumor necrosis α (TNF-α) nor chemokines, regulated on activation, T expressed secreted (RANTES), macrophage-inflammatory protein-1β (MIP-1β), MIP-1α, lymphotactin, which required for...
ABSTRACT Recent studies have shown that matrix metalloproteinases (MMPs) are induced by Mycobacterium tuberculosis during pulmonary infection. Here, expression of MMP-9 M. infection was characterized to determine whether its production correlated with disease resistance in vivo and what role, if any, might granuloma formation. Following aerosol , dissemination bacilli occurred earlier the C57BL/6 resistant mouse strain than susceptible CBA/J strain, as evident from an increased number...
Background Previously we have shown that Ag85B-TB10.4 is a highly efficient vaccine against tuberculosis when delivered in Th1 inducing adjuvant based on cationic liposomes. Another adjuvant, which has very promising profile both preclinical and clinical trials, IC31®. In this study, examined the potential of IC31® for ability to induce protection infection with Mycobacterium tuberculosis. addition, if antigen dose could influence phenotype induced T cells. Methods Findings We found...
A crucial and distinctive feature of tuberculosis infection is that Mycobacterium (Mtb) resides in granulomatous lesion at various stages disease development necrosis, an aspect little understood. We used a novel approach, applying high resolution magic angle spinning nuclear magnetic resonance spectroscopy (HRMAS NMR) directly to infected tissues, allowing us study the granulomas guinea pigs untargeted manner. Significant up-regulation lactate, alanine, acetate, glutamate, oxidized reduced...
A tuberculosis vaccine candidate consisting of a 72-kDa polyprotein or fusion protein based upon the Mtb32 and Mtb39 antigens Mycobacterium designated Mtb72F was tested for its protective capacity as potential adjunct to bovis BCG in mouse guinea pig models this disease. Formulation recombinant (rMtb72F) an AS02A adjuvant enhanced Th1 response mice but did not further reduce bacterial load lungs after aerosol challenge infection. In more stringent disease model, rMtb72F delivered by...
Section:ChooseTop of pageAbstract <<Materials and MethodsResultsDiscussionReferencesCITING ARTICLES
The kinetics of growth two virulent strains mycobacteria (M. tuberculosis Erdman and M. H37Rv) attenuated H37Ra bovis Bacillus Calmette-Guerin [BCG]) were studied in the lungs, livers, spleens, kidneys severe combined immunodeficient (SCID) mice their coisogenic CB-17 immunocompetent counterparts. It was found, keeping with findings earlier investigators (Pierce, C. H., R. J. Dubos, W. B. Schaefer. 1953. Exp. Med. 97:189.), that mice, organisms grew progressively only whereas controlled all...
Tuberculous latency and reactivation play a significant role in the pathogenesis of tuberculosis, yet mechanisms that regulate these processes remain unclear. The Mycobacterium tuberculosisuniversal stress protein (USP) homolog, rv2623, is among most highly induced genes when tubercle bacillus subjected to hypoxia nitrosative stress, conditions thought promote latency. Induction rv2623 also occurs M. tuberculosis encounters associated with growth arrest, such as intracellular milieu...
Background Recombinant adenovirus-vectored (Ad) tuberculosis (TB) vaccine platform has demonstrated great potential to be used either as a stand-alone or boost in murine models. However, Ad TB remains evaluated more relevant and sensitive guinea pig model of pulmonary TB. Many candidates shown effective models have subsequently failed pass the test Methods Findings Specific pathogen-free pigs were immunized with BCG, AdAg85A intranasally (i.n), intramuscularly (i.m), BCG boosted i.n, i.m,...
The live attenuated Mycobacterium bovis strain, Bacille Calmette Guérin (BCG) is a potent innate immune stimulator. In the C57BL/6 mouse model of tuberculosis, BCG vaccination leads to significant reduction tuberculosis burden after aerogenic infection. Our studies indicated that induced protection against pulmonary was independent T cells and present as early 7 days vaccination. This showed longevity, it did not wane when conventional cell TNF- deficient mice were infected 30...
In the lungs of mice vaccinated with Mycobacterium bovis BCG, there was an accumulation CD4 cells expressing activated effector phenotype CD44hi CD62 ligandlo) (CD62Llo) which were capable secreting gamma interferon. Upon cell transfer, however, a resting/naïve (CD44lo CD62Lhi) protecting recipients from virulent challenge infection, suggesting emergence T-cell memory within this subset.
Purified protein derivative ( PPD ) has served as a safe and effective diagnostic reagent for 60 years is the only broadly available material to diagnose latent tuberculosis infections. This also used standard control number of in vitro immunological assays. Nevertheless, molecular composition specific products that contribute extraordinary reactivity are poorly defined. Here, proteomic approach was applied elucidate gene U . S F ood D rug A dministration FDA ‐ 2. Many known M ycobacterium T...
New approaches consisting of ‘multistage’ vaccines against (TB) are emerging that combine early antigenic proteins with latency‐associated antigens. In this study, HspX was tested for its potential to elicit both short‐ and long‐term protective immune responses. is a logical component in vaccine strategies targeting responses primary infection, as well reactivation latent because previously shown, it produced during latency, our studies show, elicits protection within 30 days infection....
In the last decade, there were 10 million new tuberculosis cases per year globally. Around 9.5% of these caused by isoniazid resistant (INHr) Mycobacterium (Mtb) strains. Although resistance in Mtb is multigenic, mutations catalase-peroxidase (katG) gene predominate among INHr The effect drug-resistance-conferring on fitness and virulence variable. Here, we assessed differences bacterial growth, immune response pathology induced strains harboring at N-terminus katG gene. We studied one...
Depleting thymectomized mice of CD4+ T cells, or plus CD8+ rendered them incapable resolving Bacillus-Calmette-Guerin (BCG) infection in their lives, spleens, kidneys, and lungs. However, it did not render stabilizing the latter three organs after an initial period BCG growth. Athymic nude showed a similar capacity to control growth these certain stage infection. In contrast, congenitally severe combined immunodeficient (SCID) appeared offer no resistance infection, that organism grew...
HLA-B-associated transcript 3 (BAT3), also known as Scythe or BAG6, is a nuclear protein implicated in the control of apoptosis and natural killer (NK) cell-dendritic cell (DC) interaction. We demonstrate that BAT3 modulates immune response by regulating function macrophages. released macrophages vitro it down-regulates nitric oxide proinflammatory cytokines release IFN-γ LPS stimulated Furthermore, Mycobacterium tuberculosis-derived ESAT-6 (Rv3875) induced transient increase expression show...
Mycobacterium tuberculosis (M. tuberculosis), the causative agent of human (TB), is estimated to be harbored by up 2 billion people in a latent TB infection (LTBI) state. The only vaccine approved for use humans, BCG, does not confer protection against establishment or reactivation from LTBI, so new candidates are needed specifically address this need. Following hypothesis that mycobacterial biofilms resemble aspects we modified BCG deleting BCG1419c gene create strain. In study, compared...
In the absence of a validated animal model and/or an immune correlate which predict vaccine-mediated protection, large-scale clinical trials are currently only option to prove efficacy new tuberculosis candidate vaccines. Tools facilitate testing (TB) vaccines therefore urgently needed.We present here optimized ex vivo mycobacterial growth inhibition assay (MGIA) using murine Mycobacterium infection model. This assesses combined ability host cells inhibit in response vaccination. C57BL/6...