Trends in Molecular Medicine
Volume 18, Issue 10, Pages 575-626 (October 2012)
Lipidated promiscuous peptides vaccine for tuberculosis-endemic regions
Uthaman Gowthaman, Pradeep K. Rai, Nargis Khan, David C. Jackson, Javed N. Agrewala
Despite nine decades of Bacillus Calmette–Guérin (BCG) vaccination, tuberculosis continues to be a major global health challenge. Clinical trials worldwide have proved the inadequacy of the BCG vaccine in preventing the manifestation of pulmonary tuberculosis in adults. Ironically, the efficacy of BCG is poorest in tuberculosis endemic areas. Factors such as nontuberculous or environmental mycobacteria and helminth infestation have been suggested to limit the efficacy of BCG. Hence, in high TB-burden countries, radically novel strategies of vaccination are urgently required. Here we showcase the properties of lipidated promiscuous peptide vaccines that target and activate cells of the innate and adaptive immune systems by employing a Toll-like receptor-2 agonist, S-[2,3-bis(palmitoyloxy)propyl]cysteine (Pam2Cys). Such a strategy elicits robust protection and enduring memory responses by type 1 T helper cells (Th1). Consequently, lipidated peptides may yield a better vaccine than BCG.