Publications by authors named "Bryan E Hart"
Buruli ulcer (BU) vaccine design faces similar challenges to those observed during development of prophylactic tuberculosis treatments. Multiple BU vaccine candidates, based upon Mycobacterium bovis BCG, altered Mycobacterium ulcerans (MU) cells, recombinant MU DNA, or MU protein prime-boosts, have shown promise by conferring transient protection to mice against the pathology of MU challenge. Recently, we have shown that a recombinant BCG vaccine expressing MU-Ag85A (BCG MU-Ag85A) displayed the highest level of protection to date, by significantly extending the survival time of MU challenged mice compared to BCG vaccination alone.
View Article and Find Full Text PDFBuruli ulcer, an emerging tropical disease caused by Mycobacterium ulcerans (MU), is characterized by disfiguring skin necrosis and high morbidity. Relatively little is understood about the mode of transmission, pathogenesis, or host immune responses to MU infection. Due to significant reduction in quality of life for patients with extensive tissue scarring, and that a disproportionately high percentage of those affected are disadvantaged children, a Buruli ulcer vaccine would be greatly beneficial to the worldwide community.
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- The BCG vaccine strain is being used to create stable recombinant vaccines expressing HIV and SIV antigens, which is significant due to its established safety profile.
- A method involving leucine auxotrophic complementation was developed to ensure the consistent expression and stability of these recombinant strains.
- Quality control measures confirmed the stability and efficiency of antigen production, leading to successful immune responses in mice, thus increasing confidence in the vaccine's potential for use in immunogenicity studies.
Article Synopsis
- Researchers found that the I602S variant of the TLR1 gene restricts immune response and helps protect against diseases like leprosy and tuberculosis by reducing cell surface trafficking of TLR1.
- Individuals with the TLR1 602S variant show increased resistance to immune system suppression caused by mycobacteria, leading to better activation of macrophages and preservation of key immune functions.
- The variant might protect the host by allowing immune cells to better handle soluble mycobacterial products, which could prevent them from being disarmed before facing whole mycobacterial pathogens.
Article Synopsis
- Genetic studies on leprosy have found various genetic variations linked to how individuals respond to Mycobacterium leprae infection, especially within immune system genes.
- Research has shown that Toll-like receptors (TLRs) are key players in the immune response against microbes, including the bacteria causing leprosy and tuberculosis.
- The paper discusses the impact of specific TLR gene variations on their function, suggesting that these differences may affect the immune system's ability to recognize and combat mycobacterial infections effectively.
The subcellular localization of Toll-like receptors (TLRs) is critical to their ability to function as innate immune sensors of microbial infection. We previously reported that an I602S polymorphism of human TLR1 is associated with aberrant trafficking of the receptor to the cell surface, loss of responses to TLR1 agonists, and differential susceptibility to diseases caused by pathogenic mycobacteria. Through an extensive analysis of receptor deletion and point mutants we have discovered that position 602 resides within a short 6 amino acid cytoplasmic region that is required for TLR1 surface expression.
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