Browsing by Author "Mori, Tomi"

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    CD81 T Cells Provide an Immunologic Signature of Tuberculosis in Young Children
    (American Thoracic Society, 2011) Lancioni, Christina; Nyendak, Mellisa; Sarah Zalwango, Sarah Kiguli; Mori, Tomi; Mayanja-Kizza, Harriet; Balyejusa, Stephen; Null, Megan; Baseke, Joy; Mulindwa, Deo; Byrd, Laura; Swarbrick, Gwendolyn; Scott, Christine; Johnson, Denise F.; Malone, LaShaunda; Mudido-Musoke, Philipa; Boom, Henry; Lewinsohn, David M.; Lewinsohn, Deborah A.
    Mycobacterium tuberculosis (Mtb), the etiology of tuberculosis (TB), causes over 9 million cases of disease and 1.7 million deaths annually (1). The only available vaccine to prevent TB, bacillus Calmette-Gue´ rin, offers little protection against the most common disease manifestations (2) and efforts to develop an improved vaccine are hampered by poor understanding of immunologic events that occur after Mtb exposure. Scientific studies of immunologic responses to initial Mtb infection are difficult because most individuals living in TB-endemic settings have experienced multiple Mtb exposures. Young children, however, suffer disproportionately after exposure to Mtb, because they are at substantial risk for developing TB after primary infection (3–5). Therefore, young children with TB offer a valuable window into the human immune response to primary Mtb infection.
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    Comprehensive definition of human immunodominant CD8 antigens in tuberculosis
    (NPJ vaccines, 2017) Lewinsohn, Deborah A.; Swarbrick, Gwendolyn M.; Park, Byung; Cansler, Meghan E.; Null, Megan D.; Toren, Katelynne G.; Baseke, Joy; Zalwango, Sarah; Mayanja-Kizza, Harriet; Malone, LaShaunda L.; Nyendak, Melissa; Wu, Guanming; Guinn, Kristi; McWeeney, Shannon; Mori, Tomi; Chervenak, Keith A.; Sherman, David R.; Boom, W. Henry; Lewinsohn, David M.
    Despite widespread use of the Bacillus Calmette-Guerin vaccine, tuberculosis, caused by infection with Mycobacterium tuberculosis, remains a leading cause of morbidity and mortality worldwide. As CD8+ T cells are critical to tuberculosis host defense and a phase 2b vaccine trial of modified vaccinia Ankara expressing Ag85a that failed to demonstrate efficacy, also failed to induce a CD8+ T cell response, an effective tuberculosis vaccine may need to induce CD8+ T cells. However, little is known about CD8, as compared to CD4, antigens in tuberculosis. Herein, we report the results of the first ever HLA allele independent genome-wide CD8 antigen discovery program. Using CD8+ T cells derived from humans with latent tuberculosis infection or tuberculosis and an interferon-γ ELISPOT assay, we screened a synthetic peptide library representing 10% of the Mycobacterium tuberculosis proteome, selected to be enriched for Mycobacterium tuberculosis antigens. We defined a set of immunodominant CD8 antigens including part or all of 74 Mycobacterium tuberculosis proteins, only 16 of which are previously known CD8 antigens. Immunogenicity was associated with the degree of expression of mRNA and protein. Immunodominant antigens were enriched in cell wall proteins with preferential recognition of Esx protein family members, and within proteins comprising the Mycobacterium tuberculosis secretome. A validation study of immunodominant antigens demonstrated that these antigens were strongly recognized in Mycobacterium tuberculosisinfected individuals from a tuberculosis endemic region in Africa. The tuberculosis vaccine field will likely benefit from this greatly increased known repertoire of CD8 immunodominant antigens and definition of properties of Mycobacterium tuberculosis proteins important for CD8 antigenicity.