Towards new TB vaccines

Abstract

Mycobacterium tuberculosis remains the leading cause of death attributed to a single infectious organism. Bacillus Calmette-Guerin (BCG), the standard vaccine against M. tuberculosis, is thought to prevent only 5% of all vaccine-preventable deaths due to tuberculosis, thus an alternative vaccine is required. One of the principal barriers to vaccine development against M. tuberculosis is the complexity of the immune response to infection, with uncertainty as to what constitutes an immunological correlate of protection. In this paper, we seek to give an overview of the immunology of M. tuberculosis infection, and by doing so, investigate possible targets of vaccine development. This encompasses the innate, adaptive, mucosal and humoral immune systems. Though MVA85A did not improve protection compared with BCG alone in a large-scale clinical trial, the correlates of protection this has revealed, in addition to promising results from candidate such as VPM1002, M72/ASO1E and H56:IC31 point to a brighter future in the field of TB vaccine development.

PE_PGRS33, an Important Virulence Factor of Mycobacterium tuberculosis and Potential Target of Host Humoral Immune Response

“…In the last two decades, significant progress has been made in the search for a better vaccine against TB [ 19 , 20 , 21 , 22 , 23 , 24 ]. Table 1 provides an overview of the main TB vaccine candidates currently in clinical development and reports their composition.…”

Recent Advances in the Development of Protein- and Peptide-Based Subunit Vaccines against Tuberculosis

“…Conversely, a limited protective effect was observed against pulmonary TB, especially in adults, which is not only the most prevalent form of the disease but also the principal source of transmission [ 10 ]. Epidemiological evidence highlighted that the BCG degree of protection varies geographically [ 6 , 7 , 8 , 11 , 12 , 13 , 14 , 15 ], while several studies suggested a lower and short-lasting BCG protection in people previously sensitized with Mtb and non-tuberculous mycobacteria (NTB) [ 7 , 11 ]. Additionally, it has an unfavorable risk profile in immunocompromised conditions, for example, congenital immunodeficiencies and HIV infections, because of BCG bacteremia that follows vaccination [ 9 , 13 ].…”

“…Mtb infection is a complex, multi-stage process that generally arises after the inhalation of Mtb -containing aerosolized droplets released from people with active pulmonary TB ( Figure 1 ). The respiratory tract and bronchoalveolar spaces represent a unique immunological compartment where the innate immune system and the respiratory epithelium act as the first barrier to providing early clearance of the pathogen [ 11 , 16 , 17 , 18 , 19 ]. Following initial exposure to Mtb , a small percentage of exposed humans can quickly clear the infection.…”

Immunological Characterization of Proteins Expressed by Genes Located in Mycobacterium tuberculosis-Specific Genomic Regions Encoding the ESAT6-like Proteins

“…Furthermore, the immune responses induced by cross-reactive antigens due to exposure to environmental mycobacteria lead to an early clearance of antigens in the BCG vaccine, which prevents an effective immune response from being generated, rendering it a failure, and hence causing a blocking effect [ 21 , 22 , 23 , 24 ]. The use of M. tuberculosis -specific antigens as subunit vaccines is expected to overcome the problems of blocking or masking effects [ 25 , 26 , 27 , 28 ].…”

“…BCG vaccination also faces a problem in the diagnosis of TB by using the widely used antigenic preparation of M. tuberculosis known as the purified protein derivative (PPD), in the tuberculin skin test, due to the presence of the cross-reactive antigens [ 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. It is expected that M. tuberculosis -specific antigens may overcome the problem of diagnostic inaccuracy associated with the use of PPD in BCG-vaccinated people [ 35 , 36 , 37 , 38 , 39 , 40 ].…”