What’s New in the Development of Tuberculosis Vaccines

Abstract

United Kingdom) [3] . Furthermore, as BCG is a live mycobacterium [4] , it is not suitable for vaccinating immunocompromised individuals, particularly HIV/AIDS patients, due to the possibility of causing disease in such individuals. Since BCG vaccination induces positivity to the commonly used tuberculin skin test for the diagnosis of TB, it becomes difficult to use this test for diagnostic or epidemiological investigations in populations vaccinated with BCG [3] . Therefore, the development of new vaccines based on M. tuberculosis -specific antigens is urgently needed. The identification of M. tuberculosis -specific antigens has been facilitated by advances in mycobacterial genome sequencing and the comparative genomics to identify M. tuberculosis -specific genomic regions. Such studies have identified 11 M. tuberculosis -specific genomic regions known as regions of differences (RDs), which are deleted/absent in all BCG substrains currently used in different parts of the world to vaccinate against TB [5] . In silico analysis has suggested that these RDs can potentially encode 89 proteins [5] . To identify the candidate proteins suitable for vaccine development, it is essential to identify the immunodominant proteins from the RDs that can mediate protection against TB. Protection in TB is primarily mediated by cellular immunity involving the interaction of antigen-specific T cells and macrophages [6] . This interaction is often indicated by antigen-induced proliferation of T cells and is dependent on the interplay of cytokines secreted by these cells. Although a broad spectrum of cytokines contribute Tuberculosis (TB) is a major infectious disease problem of worldwide prevalence and ranks among the top 10 causes of global mortality. The most recent estimates by the World Health Organization suggest that there were 9.4 million incidence cases, and 1.7 million people died of TB in 2009 [1] . About one third of the world population is estimated to be latently infected with Mycobacterium tuberculosis , and at least 10% of these people will develop active disease in their lifetime. In spite of worldwide efforts to control TB, the global burden of the disease is increasing, particularly among the poor developing countries of Asia and Africa [1] . This is due to many reasons, including wars and immigration, poverty and malnutrition, HIV-TB co-infection and the increasing prevalence of multi-drug resistant and excessive drug-resistant TB [1] . The worldwide control of TB requires development of new drugs, cost-effective methods/reagents for specific diagnosis and new vaccines [2, 3] . Among these possibilities, the development of new vaccines deserves priority because effective vaccines are the best weapons to fight against infectious diseases [2] . The currently available vaccine against TB is a live attenuated strain of pathogenic Mycobacterium bovis known as Bacillus Calmette-Guerin (BCG). Although BCG has been widely used to vaccinate against TB since 1921, it is the most controversial vaccine in current use. This is because BCG has failed to consistently protect against the major manifestation of TB in adults, i.e. pulmonary TB [3] . The variations in protection have ranged from nil (e.g. in India and Malawi) to 80% (e.g. in the Received: March 6, 2012 Accepted: March 8, 2012 Published online: April 5, 2012