title: Mycobacterial membrane vesicles administered systemically in mice induce a protective immune response to surface compartments of Mycobacterium tuberculosis.
abstract: Pathogenic and nonpathogenic species of bacteria and fungi release membrane vesicles (MV), containing proteins, polysaccharides, and lipids, into the extracellular milieu. Previously, we demonstrated that several mycobacterial species, including bacillus Calmette-Guerin (BCG) and Mycobacterium tuberculosis, release MV containing lipids and proteins that subvert host immune response in a Toll-like receptor 2 (TLR2)-dependent manner (R. Prados-Rosales et al., J. Clin. Invest. 121:1471-1483, 2011, doi:10.1172/JCI44261). In this work, we analyzed the vaccine potential of MV in a mouse model and compared the effects of immunization with MV to those of standard BCG vaccination. Immunization with MV from BCG or M. tuberculosis elicited a mixed humoral and cellular response directed to both membrane and cell wall components, such as lipoproteins. However, only vaccination with M. tuberculosis MV was able to protect as well as live BCG immunization. M. tuberculosis MV boosted BCG vaccine efficacy. In summary, MV are highly immunogenic without adjuvants and elicit immune responses comparable to those achieved with BCG in protection against M. tuberculosis.
  
  
  OBJECTIVE
  This work offers a new vaccine approach against tuberculosis using mycobacterial MV. Mycobacterium MV are a naturally released product combining immunogenic antigens in the context of a lipid structure. The fact that MV do not need adjuvants and elicit protection comparable to that elicited by the BCG vaccine encourages vaccine approaches that combine protein antigens and lipids. Consequently, mycobacterium MV establish a new type of vaccine formulation.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx NY, USA rafael.prados-rosales@einstein.yu.edu.
authors.forename: Rafael
authors.initials: R
authors.lastname: Prados-Rosales
authors.forename: Leandro J
authors.initials: LJ
authors.lastname: Carreño
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx NY, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Batista-Gonzalez
authors.affiliation: Grupo de Inmunologia Celular e Inmunogenetica, Departamento de Microbiologia y Parasitologia, Facultad de Medicina, Universidad de Antioquia, Medellin, Colombia.
authors.forename: Andres
authors.initials: A
authors.lastname: Baena
authors.forename: Manjunatha M
authors.initials: MM
authors.lastname: Venkataswamy
authors.forename: Jiayong
authors.initials: J
authors.lastname: Xu
authors.affiliation: Virginia G. Piper Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, Arizona, USA.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Yu
authors.affiliation: Virginia G. Piper Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, Arizona, USA.
authors.forename: Garrick
authors.initials: G
authors.lastname: Wallstrom
authors.affiliation: Virginia G. Piper Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, Arizona, USA.
authors.forename: D Mitchell
authors.initials: DM
authors.lastname: Magee
authors.affiliation: Virginia G. Piper Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, Arizona, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: LaBaer
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Achkar
authors.forename: William R
authors.initials: WR
authors.lastname: Jacobs
authors.forename: John
authors.initials: J
authors.lastname: Chan
authors.forename: Steven A
authors.initials: SA
authors.lastname: Porcelli
authors.forename: Arturo
authors.initials: A
authors.lastname: Casadevall
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001500:BCG Vaccine / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D056724:Immunity, Humoral; D007113:Immunity, Innate; D008074:Lipoproteins / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology; D014376:Tuberculosis / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001500:BCG Vaccine; D008074:Lipoproteins; D008565:Membrane Proteins; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D032581:Tuberculosis Vaccines