Treponema pallidum specific CD4 T cell epitope discovery

Abstract

Abstract Despite curative therapy and multiple public health campaigns to eliminate syphilis in the US, the incidence of Syphilis is rising in diverse groups: men who have sex with men, women, and children. An effective syphilis vaccine will be a key tool in the eradication of this disease. Prior efforts to create a protective syphilis vaccine focused on raising antibodies against rare outer membrane proteins to facilitate antibody mediated opsonophagocytosis of Treponema pallidum (Tp) in infectious lesions. The inclusion of immunodominant T cell antigens in a subunit vaccine can provide CD4 T cell help to B cells to produce opsonic antibodies. We sought to identify human Tp T cell antigens validated to the epitope level as there are none reported in the literature. Tp specific CD4 T cells were isolated from persons with active or treated syphilis infection by CD137 and CD69 activation–based FACS and polyclonal expansion. These cells were then probed with a panel of 39 recombinantly expressed Tp proteins. Preliminary data show that activation-induced-marker-enriched, expanded T cells can be probed to discover novel CD4 T cell antigens and epitopes using proliferation experiments. The first 4 CD4 T cell antigens identified included antibody targets Tp0435 and Tp0574, a flagellar apparatus protein Tp0870, and a metabolite transporter Tp0684. Further refinement of minimal T cell antigens within these proteins and expansion of the Tp protein panel is ongoing. These are the first human Tp specific T cell epitopes described. Incorporating this information into vaccine design may further increase protection against infection. Supported by T32AI007140-44