ag-85 and Tuberculosis

Mycobacterium tuberculosis (Mtb) is one of the most life-threatening mycobacterial species which is increasing the death rate due to emerging multi-drug resistant (MDR) strains. Concerned health authorities worldwide are interested in developing an effective vaccine to prevent the spread of Mtb. After years of research, including successful identification of many Mtb immunogenic molecules, effective therapeutic agents or a vaccine have yet to be found. However, among the identified Mtb immunogenes, antigen 85 (Ag85) complex (Ag85A, Ag85B, and Ag85C) is receiving attention from scientists as it allows bacteria to evade the host immune response by preventing formation of phagolysosomes for eradication of infection. Due to their importance, A85 molecules are being utilized as tools in diagnostic methods and in the construction of new vaccines, such as recombinant attenuated vaccines, DNA vaccines, and subunit vaccines. This paper represents a comprehensive review of studies on Mtb molecules examining pathogenicity, biochemistry, immunology, and the role of Mtb in therapeutic or vaccine research.

Topics: Acyltransferases; Animals; Antigens, Bacterial; Bacterial Proteins; Drug Design; Humans; Immunity, Cellular; Indoles; Mycobacterium tuberculosis; Tuberculosis; Tuberculosis Vaccines; Tuberculosis, Multidrug-Resistant; Vaccines, Attenuated; Vaccines, DNA; Vaccines, Subunit; Vaccines, Synthetic; Virulence; Virulence Factors

The development of a new and improved vaccine against tuberculosis has in the last 10 years been accelerated tremendously from the completed Mycobacterium tuberculosis genome and the progress in molecular biology. This has resulted in the identification of a large number of antigens with potential in tuberculosis vaccines. The next phase of this work has now started--putting the most relevant molecules back together as fusion molecules and cocktails. This requires carefully monitoring of aspects as immunodominance, recognition in different populations as well as the influence of different adjuvants and delivery systems. The most advanced of these vaccines such as the fusion between ESAT6 and Ag85B have been evaluated in a range of animal models including non-human primates and are now entering into clinical trials. For these vaccines to be successfully implemented in future vaccination programmes it is necessary to understand the immunological background for the failure of BCG and optimize the vaccines for their ability to boost the immuno-response primed by BCG.

Topics: Animals; Antigens, Bacterial; Bacterial Proteins; BCG Vaccine; Cattle; Drug Design; Humans; Immunization, Secondary; Indoles; Mice; Mycobacterium tuberculosis; Tuberculosis; Tuberculosis Vaccines