title: Enhanced control of Mycobacterium tuberculosis extrapulmonary dissemination in mice by an arabinomannan-protein conjugate vaccine.
abstract: Currently there are a dozen or so of new vaccine candidates in clinical trials for prevention of tuberculosis (TB) and each formulation attempts to elicit protection by enhancement of cell-mediated immunity (CMI). In contrast, most approved vaccines against other bacterial pathogens are believed to mediate protection by eliciting antibody responses. However, it has been difficult to apply this formula to TB because of the difficulty in reliably eliciting protective antibodies. Here, we developed capsular polysaccharide conjugates by linking mycobacterial capsular arabinomannan (AM) to either Mtb Ag85b or B. anthracis protective antigen (PA). Further, we studied their immunogenicity by ELISA and AM glycan microarrays and protection efficacy in mice. Immunization with either Abg85b-AM or PA-AM conjugates elicited an AM-specific antibody response in mice. AM binding antibodies stimulated transcriptional changes in Mtb. Sera from AM conjugate immunized mice reacted against a broad spectrum of AM structural variants and specifically recognized arabinan fragments. Conjugate vaccine immunized mice infected with Mtb had lower bacterial numbers in lungs and spleen, and lived longer than control mice. These findings provide additional evidence that humoral immunity can contribute to protection against Mtb.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx NY, United States of America.|CIC bioGUNE, Bizkaia Technology Park, Derio, Bizkaia, Spain.
authors.forename: Rafael
authors.identifier: 0000-0001-5964-0166
authors.initials: R
authors.lastname: Prados-Rosales
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx NY, United States of America.|Millennium Institute on Immunology and Immunotherapy, Programa Disciplinario de Inmunologia, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Leandro
authors.initials: L
authors.lastname: Carreño
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx NY, United States of America.|Department of Medicine, Albert Einstein College of Medicine, Bronx NY, United States of America.
authors.forename: Tingting
authors.identifier: 0000-0002-2227-3208
authors.initials: T
authors.lastname: Cheng
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx NY, United States of America.|Department of Medicine, Albert Einstein College of Medicine, Bronx NY, United States of America.
authors.forename: Caroline
authors.initials: C
authors.lastname: Blanc
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx NY, United States of America.|Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx NY, United States of America.
authors.forename: Brian
authors.identifier: 0000-0003-0880-4487
authors.initials: B
authors.lastname: Weinrick
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx NY, United States of America.|Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx NY, United States of America.
authors.forename: Adel
authors.identifier: 0000-0002-4171-972X
authors.initials: A
authors.lastname: Malek
authors.affiliation: Alberta Glycomics Centre and Department of Chemistry, University of Alberta, Gunning-Lemieux Chemistry Center, Edmonton, Alberta, Canada.
authors.forename: Todd L
authors.identifier: 0000-0002-8331-8211
authors.initials: TL
authors.lastname: Lowary
authors.affiliation: Grupo de Inmunologia Celular e inmunogenetica, Universidad de Antioquia, Medellin, Colombia.
authors.forename: Andres
authors.identifier: 0000-0003-1309-1020
authors.initials: A
authors.lastname: Baena
authors.affiliation: Alberta Glycomics Centre and Department of Chemistry, University of Alberta, Gunning-Lemieux Chemistry Center, Edmonton, Alberta, Canada.
authors.forename: Maju
authors.identifier: 0000-0003-0664-5275
authors.initials: M
authors.lastname: Joe
authors.affiliation: Alberta Glycomics Centre and Department of Chemistry, University of Alberta, Gunning-Lemieux Chemistry Center, Edmonton, Alberta, Canada.
authors.forename: Yu
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Institute for Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany.
authors.forename: Rainer
authors.identifier: 0000-0002-3378-2067
authors.initials: R
authors.lastname: Kalscheuer
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx NY, United States of America.
authors.forename: Ana
authors.initials: A
authors.lastname: Batista-Gonzalez
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx NY, United States of America.
authors.forename: Noemi A
authors.initials: NA
authors.lastname: Saavedra
authors.affiliation: CIC bioGUNE, Bizkaia Technology Park, Derio, Bizkaia, Spain.
authors.forename: Leticia
authors.initials: L
authors.lastname: Sampedro
authors.affiliation: CIC bioGUNE, Bizkaia Technology Park, Derio, Bizkaia, Spain.
authors.forename: Julen
authors.initials: J
authors.lastname: Tomás
authors.affiliation: CIC bioGUNE, Bizkaia Technology Park, Derio, Bizkaia, Spain.|Ikerbasque, Basque Foundation for Science, Bilbao, Bizkaia, Spain.
authors.forename: Juan
authors.identifier: 0000-0003-2061-7182
authors.initials: J
authors.lastname: Anguita
authors.affiliation: Genomics Research Center, Academia Sinica, Section 2, Nankang, Taipei, Taiwan.
authors.forename: Shang-Cheng
authors.initials: SC
authors.lastname: Hung
authors.affiliation: Genomics Research Center, Academia Sinica, Section 2, Nankang, Taipei, Taiwan.
authors.forename: Ashish
authors.initials: A
authors.lastname: Tripathi
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx NY, United States of America.|Department of Medicine, Albert Einstein College of Medicine, Bronx NY, United States of America.
authors.forename: Jiayong
authors.initials: J
authors.lastname: Xu
authors.affiliation: Infectious Diseases Unit, Israel Center for Disease Control, Israel Ministry of Health, Tel Hashomer, Israel.|Department of Pediatrics, and Department of Family and Community Medicine, New York Medical College, Valhalla, NY, United States of America.
authors.forename: Aharona
authors.initials: A
authors.lastname: Glatman-Freedman
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx NY, United States of America.|Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx NY, United States of America.
authors.forename: Williams R
authors.initials: WR
authors.lastname: Jacobs
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx NY, United States of America.|Department of Medicine, Albert Einstein College of Medicine, Bronx NY, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Chan
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx NY, United States of America.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Porcelli
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx NY, United States of America.|Department of Medicine, Albert Einstein College of Medicine, Bronx NY, United States of America.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Achkar
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx NY, United States of America.|Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America.
authors.forename: Arturo
authors.identifier: 0000-0002-9402-9167
authors.initials: A
authors.lastname: Casadevall
mesh_terms: D000217:Acyltransferases / Q000276:immunology; D019264:Adoptive Transfer; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D056724:Immunity, Humoral / Q000276:immunology; D008351:Mannans / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D009169:Mycobacterium tuberculosis / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D014376:Tuberculosis / Q000276:immunology*; D032581:Tuberculosis Vaccines / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D008351:Mannans; D032581:Tuberculosis Vaccines; D018074:Vaccines, Conjugate; C030325:anthrax toxin; C012189:arabinomannan; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis