Trends in Molecular Medicine
Volume 18, Issue 9, Pages 503-574 (September 2012)
http://www.sciencedirect.com/science/journal/14714914

Articles in Press
Lipidated promiscuous peptides vaccine for tuberculosis-endemic regions
Review Article
In Press, Corrected Proof, Available online 30 August 2012
Uthaman Gowthaman, Pradeep K. Rai, Nargis Khan, David C. Jackson, Javed N. Agrewala

Abstract
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.