title: Current efforts and future prospects in the development of live mycobacteria as vaccines.
abstract: The development of more effective vaccines against Mycobacterium tuberculosis (Mtb) remains a major goal in the effort to reduce the enormous global burden of disease caused by this pathogen. Whole-cell vaccines based on live mycobacteria with attenuated virulence represent an appealing approach, providing broad antigen exposure and intrinsic adjuvant properties to prime durable immune responses. However, designing vaccine strains with an optimal balance between attenuation and immunogenicity has proven to be extremely challenging. Recent basic and clinical research efforts have broadened our understanding of Mtb pathogenesis and created numerous new vaccine candidates that have been designed to overcome different aspects of immune evasion by Mtb. In this review, we provide an overview of the current efforts to create improved vaccines against tuberculosis based on modifications of live attenuated mycobacteria. In addition, we discuss the use of such vaccine strains as vectors for stimulating protective immunity against other infectious diseases and cancers.
authors.affiliation: a 1 Albert Einstein College of Medicine - Microbiology & Immunology, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Tony W
authors.initials: TW
authors.lastname: Ng
authors.affiliation: a 1 Albert Einstein College of Medicine - Microbiology & Immunology, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Noemí A
authors.initials: NA
authors.lastname: Saavedra-Ávila
authors.affiliation: a 1 Albert Einstein College of Medicine - Microbiology & Immunology, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Kennedy
authors.affiliation: a 1 Albert Einstein College of Medicine - Microbiology & Immunology, 1300 Morris Park Avenue, Bronx, NY 10461, USA.|b 2 Millennium Institute on Immunology and Immunotherapy, Programa Disciplinario de Inmunologia, Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Leandro J
authors.initials: LJ
authors.lastname: Carreño
authors.affiliation: a 1 Albert Einstein College of Medicine - Microbiology & Immunology, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Porcelli
mesh_terms: D055808:Drug Discovery / Q000379:methods* / Q000639:trends; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014376:Tuberculosis / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000276:immunology* / Q000302:isolation & purification*; D014613:Vaccines, Attenuated / Q000276:immunology / Q000302:isolation & purification
chemical_list: D032581:Tuberculosis Vaccines; D014613:Vaccines, Attenuated
keywords: Mycobacterium tuberculosis; attenuation; autophagy; auxotroph; immune evasion; live vaccine; mycobacterial antigens; phagosome; pro-apoptotic