Recent Advances in Tuberculosis Vaccine Development

Abstract

Tuberculosis is exacting a great toll on the lives of many people worldwide. Despite seemingly previous successes in controlling the disease, tuberculosis is now re-emerging as the leading cause of mortality due to infectious diseases in many parts of the world. The high incidence of the disease has been attributed mainly to its combination with HIV infection and the emergence of multi-drug resistant strains. In addition, the low diagnostic reliability and therapeutic coverage, as well as the absence of a fully protective vaccine, configure the current situation of the disease at a worrying level. Taking into account these antecedents, it is considered that the development of an effective vaccine is the most important and urgent element for the control of the disease. Supported by the better understanding of the immune response to the infection, the biology of Mycobacterium tuberculosis and the availability of new technologies in genomics and proteomics, a wide range of experimental vaccines have been attempted. These approaches include the use of inactivated strains; live genetically attenuated strains; live vectors expressing M. tuberculosis antigens; recombinant subunits, conjugated, and DNA vaccines as well as the combination of selected strategies in prime boost immunisations. Furthermore, the use of novel adjuvants, delivery systems and routes of immunisation have also been evaluated. Some of the candidate vaccines demonstrated significant levels of efficacy in animal models and are now in initial clinical evaluation. This review analyzes the main aspects related to the development of new generation vaccines against tuberculosis, as well as the challenges and complexities inherent to this endeavour.

The Role of Antibodies in the Defense Against Tuberculosis

“…Prophylactic use of antibodies could be applied in recent contacts of TB patients, with special attention to risk groups [84]. In this regard, successful prophylactic use of antibodies in exposed individuals has been shown in the case of several other pathogens such as varicella, tetanus, Respiratory Synsicial Virus (RSV), rabies and Hepatitis B [85,86]…”

Towards a New Challenge in TB Control: Development of Antibody-Based Protection

“…Future applications of antibody formulations for the control of TB may include treatment of patients infected with Multidrug Resistant (MDR) strains, combination with the standard treatment in order to achieve faster therapeutic effects, and administration to recent contacts of TB patients with special attention to risk groups [85].…”

Immunogenicity of recombinant Mycobacterium bovis bacille Calmette–Guèrin clones expressing T and B cell epitopes of Mycobacterium tuberculosis antigens

“…WHO estimates that 8.7 million new cases and approximately 1.6 million deaths occur annually [1,2] . The current vaccine against Mycobacterium tuberculosis , M. bovis bacille Calmette–Guèrin (BCG), is the most widely used vaccine in preventing TB disease especially in childhood [3,4] . However, it has also been established that the protection afforded by BCG is highly controversial [5] .…”