Exploiting the mycobacterial cell wall to design improved vaccines against tuberculosis

Abstract

The only vaccine available against tuberculosis (TB), the Bacille Calmette-Guerin (BCG), does not provide effective protection against the most common forms of adult TB and in recent years efforts have been made to develop a new and improved vaccine. Among the strategies implemented, the generation of a new live attenuated mycobacterial strain is seen as one of the most promising and feasible, for scientific, ethical and practical reasons. The new understanding of the biology of the tubercle bacilli and of host-pathogen interaction processes, coupled with the possibility to engineer BCG or M. tuberculosis, opened new avenues to design "intelligent" vaccines, capable of eliciting the immune response associated with protection while avoiding the induction of the host immune response associated with immunopathology. The complex and highly immunogenic mycobacterial cell wall can shape the general and antigen specific immune response elicited following immunization, and the possibility to exploit this knowledge may lead to the development of new vaccines that could help conquer this ancient human disease.

The Enigmatic PE/PPE Multigene Family of Mycobacteria and Tuberculosis Vaccination

“…Also, PE-PGRSs have been shown to promote entry of M. tuberculosis into macrophages via TLR2, an important step in the pathogenesis of tuberculosis (61). PE-PGRS and other PE/PPEs can be constitutively expressed in M.…”

Mycobacterium Tuberculosis Virulence: Insights and Impact on Vaccine Development

“…The lack of evidence of the potential role of antibodies in exerting a protective activity against TB, paired with the pivotal role of T-cell immunity during M. tuberculosis infection, has led to the development of immunization strategies aimed at eliciting T-cell responses against M. tuberculosis antigens and primarily those that are actively secreted, regardless of their role and function in M. tuberculosis biology and TB pathogenesis [85]. Among the most promising candidate antigens are those secreted through the ESX-1 secretion system, such as ESAT-6 and CFP-10 [85], other highly immunogenic and secreted proteins as MPT64 and MPT83 and other secreted or cell bound antigens such as Ag85A/B, HSP65, PPE18 [83,85,101]. An active field of study aims at identifying antigens expressed in the different steps of the infectious process and specifically during the latent infection or associated with dormancy, so to generate vaccines able to elicit T-cell responses that would prevent reactivation [85].…”

Protective capacity of proteoliposomes fromMycobacterium bovisBCG in a mouse model of tuberculosis

“…4,5 Many studies support the role of mycobacterial cell wall components in the development of TB pathogenesis and therefore have been a prime target for the identification and characterization of antigens with potential application in vaccine development. [6][7][8][9] Proteoliposomes (PL) are detergent outer membrane extracts of bacteria that contain proteins, lipids and native lipopolysaccharides. 10 Only a few PL-based vaccines are licensed, one of them, VA-MENGOC-BC Ò , is a vaccine composed of PL obtained from the outer membrane of Neisseria meningitidis serogroup B.…”