Immunotherapy for human TB: evidence for adjuvant activities of some host defense peptides against TB.

Abstract

Introduction TB remains a major worldwide health concern, with 9.4 million newly emerging active TB cases and 1.7 million reported deaths annually [1]. According to recent data from the WHO, a third of the world’s population is infected with Mycobacterium tuberculosis, the etiologic agent of TB [2]. This is due to many reasons, such as because M. tuberculosis has evolved complex strategies for persistence in the human host. In addition, enhanced susceptibility to TB in HIV-infected populations and multidrug-resistant TB has been increasing in incidence in many countries during the past decade. The current vaccine in use against TB is Mycobacterium bovis Bacillus Calmette–Guerin (BCG). However, its efficacy of protection against pulmonary TB is variable (0–80%) [3]. Moreover, BCG is a live mycobacterium, which is not suitable for vaccinating HIV/ AIDS patients. Therefore, there is a pressing need to develop new therapeutics and new vaccine adjuvants to effectively control TB. Among these possibilities, vaccination is the single most cost-effective method to control TB. Adjuvants are components of vaccines that induce stronger immune responses than can be induced by the antigen alone. In this regard, host defense peptides (HDPs) and synthetic derivatives termed innate defense regulators (IDRs) represent important components of innate immunity with adjuvant activities that have been shown to have a broad spectrum against mycobacteria. It is important to note that these IDRs are designed for selectively enhancing immunity against TB while suppressing potentially harmful excessive inflammation responses demonstrated by certain HDPs. The major groups of HDPs in humans are the defensins and a single cathelicidin, LL-37. This article reviews the weight of evidence supporting adjuvant activities of HDPs for TB.