Assessing the Potential of Monoclonal Antibodies Against Mycobacterium Tuberculosis
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CitationKawahara, Jeffrey. 2019. Assessing the Potential of Monoclonal Antibodies Against Mycobacterium Tuberculosis. Master's thesis, Harvard Medical School.
AbstractTuberculosis infects approximately one-quarter of the world’s population and is the leading cause of death by a single infectious disease, responsible for a reported 1.3 million deaths in 2017. Though Mycobacterium tuberculosis, the causative bacteria, is treatable with antibiotic therapy, the increased prevalence of drug resistant strains as well as the variable efficacy of the only widely approved vaccine have highlighted the need for novel approaches to therapeutic and vaccine development. Historically, it has been believed that the protective immune response against M. tuberculosis is attributed almost exclusively by cell-mediated immunity with humoral immunity being largely dismissed. Despite the skepticism that has surrounded the role of antibodies against this intracellular pathogen, there has been an increase in evidence suggesting that they can be involved in a variety of protective capacities. In particular, extensive study of the variable (Fab) and constant (Fc) domains has become possible in recent years, and there is a strong possibility that antigen-specificity, innate immune signaling, glycosylation patterns and other related characteristics impact a monoclonal antibody’s protective abilities. Utilizing a specially optimized version of the Golden Gate cloning system, production of mAbs with chosen Fab domains and immunoglobulin subclasses is possible, allowing for the assessment of the influence of each component. By confirming antigen-specific binding, ability to induce innate cell effector functions, and protection conferred against live bacterial challenge, results indicate that antibodies can potentially be important mediators of defense against this global pandemic.
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