Promiscuous Peptide of 16 kDa Antigen Linked to Pam2Cys Protects Against Mycobacterium tuberculosis by Evoking Enduring Memory T-Cell Response

作者:Gowthaman Uthaman; Singh Vijender; Zeng Weiguang; Jain Shweta; Siddiqui Kaneez F; Chodisetti Sathi Babu; Gurram Rama Krishna; Parihar Pankaj; Gupta Pushpa; Gupta Umesh D; Jackson David C; Agrewala Javed N*
来源:Journal of Infectious Diseases, 2011, 204(9): 1328-1338.
DOI:10.1093/infdis/jir548

摘要

One of the main reasons considered for BCG failure in tuberculosis-endemic areas is impediment by environmental mycobacteria in its processing and generation of memory T-cell response. To overcome this problem, we developed a unique lipopeptide (L91) by linking the promiscuous peptide (sequence 91-110) of 16 kDa antigen of Mycobacterium tuberculosis to Pam2Cys. L91 does not require extensive antigen processing and generates enduring Th1 memory response. This is evidenced by the fact that L91 significantly improved the activation, proliferation, and generation of protective T cells. Furthermore, L91 surmounts the barrier of major histocompatibility complex polymorphism and induces better protection than BCG. This peptide has self-adjuvanting properties and activates dendritic cells. Importantly, L91 activates T cells isolated from purified protein derivative-positive healthy volunteers that responded weakly to free peptide (F91). In essence, L91 can be a potent future vaccine candidate against tuberculosis.

  • 出版日期2011-11-1