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Enhanced control of Mycobacterium tuberculosis extrapulmonary dissemination in mice by an arabinomannan-protein conjugate vaccine
Indexado
WoS WOS:000398120300030
Scopus SCOPUS_ID:85016504809
DOI 10.1371/JOURNAL.PPAT.1006250
Año 2017
Tipo artículo de investigación

Citas Totales

Autores Afiliación Chile

Instituciones Chile

% Participación
Internacional

Autores
Afiliación Extranjera

Instituciones
Extranjeras


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 cellmediated 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.

Revista



Revista ISSN
P Lo S Pathogens 1553-7366

Métricas Externas



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Disciplinas de Investigación



WOS
Parasitology
Virology
Microbiology
Scopus
Sin Disciplinas
SciELO
Sin Disciplinas

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Publicaciones WoS (Ediciones: ISSHP, ISTP, AHCI, SSCI, SCI), Scopus, SciELO Chile.

Colaboración Institucional



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Autores - Afiliación



Ord. Autor Género Institución - País
1 Prados-Rosales, Rafael Hombre Albert Einstein Coll Med - Estados Unidos
CIC BioGUNE - España
Albert Einstein College of Medicine of Yeshiva University - Estados Unidos
2 CARRENO-MARQUEZ, LEANDRO JAVIER Hombre Albert Einstein Coll Med - Estados Unidos
Universidad de Chile - Chile
Albert Einstein College of Medicine of Yeshiva University - Estados Unidos
3 Cheng, Tingting - Albert Einstein Coll Med - Estados Unidos
Albert Einstein College of Medicine of Yeshiva University - Estados Unidos
4 Blanc, Caroline Mujer Albert Einstein Coll Med - Estados Unidos
Albert Einstein College of Medicine of Yeshiva University - Estados Unidos
5 Weinrick, Brian Hombre Albert Einstein Coll Med - Estados Unidos
Albert Einstein College of Medicine of Yeshiva University - Estados Unidos
6 Malek, Adel Hombre Albert Einstein Coll Med - Estados Unidos
Albert Einstein College of Medicine of Yeshiva University - Estados Unidos
7 Lowary, Todd L. Hombre Univ Alberta - Canadá
University of Alberta - Canadá
Alberta Glycomics Centre - Canadá
8 Baena, Andres Hombre UNIV ANTIOQUIA - Colombia
Universidad de Antioquia - Colombia
9 Joe, Maju - Univ Alberta - Canadá
University of Alberta - Canadá
Alberta Glycomics Centre - Canadá
10 Bai, Yu - Univ Alberta - Canadá
University of Alberta - Canadá
Alberta Glycomics Centre - Canadá
11 Kalscheuer, Rainer Hombre Heinrich Heine Univ Duesseldorf - Alemania
Heinrich-Heine-Universität Düsseldorf - Alemania
12 Batista-Gonzalez, Ana - Albert Einstein Coll Med - Estados Unidos
Albert Einstein College of Medicine of Yeshiva University - Estados Unidos
13 Saavedra-Avila, Noemi Alejandra Mujer Albert Einstein Coll Med - Estados Unidos
Albert Einstein College of Medicine of Yeshiva University - Estados Unidos
14 Sampedro, Leticia Mujer CIC BioGUNE - España
15 Tomas, Julen Hombre CIC BioGUNE - España
16 Anguita, Juan Hombre CIC BioGUNE - España
Basque Fdn Sci - España
Ikerbasque, the Basque Foundation for Science - España
Ikerbasque, Basque Foundation for Science - España
17 Hung, Shang-Cheng - Acad Sinica - Taiwán
Academia Sinica, Genomics Research Center - Taiwán
18 Tripathi, Ashish Hombre Acad Sinica - Taiwán
Academia Sinica, Genomics Research Center - Taiwán
19 Xu, Jiayong - Albert Einstein Coll Med - Estados Unidos
Albert Einstein College of Medicine of Yeshiva University - Estados Unidos
20 Glatman-Freedman, Aharona - Israel Minist Hlth - Israel
NEW YORK MED COLL - Estados Unidos
Israel Ministry of Health - Israel
New York Medical college - Estados Unidos
21 JACOBS, WILLIAMS R., JR. Hombre Albert Einstein Coll Med - Estados Unidos
Albert Einstein College of Medicine of Yeshiva University - Estados Unidos
22 Chan, John Hombre Albert Einstein Coll Med - Estados Unidos
Albert Einstein College of Medicine of Yeshiva University - Estados Unidos
23 Porcelli, Steven A. Hombre Albert Einstein Coll Med - Estados Unidos
Albert Einstein College of Medicine of Yeshiva University - Estados Unidos
24 Achkar, Jacqueline M. Mujer Albert Einstein Coll Med - Estados Unidos
Albert Einstein College of Medicine of Yeshiva University - Estados Unidos
25 Casadevall, Arturo Hombre Albert Einstein Coll Med - Estados Unidos
Johns Hopkins Bloomberg Sch Publ Hlth - Estados Unidos
Albert Einstein College of Medicine of Yeshiva University - Estados Unidos
Johns Hopkins Bloomberg School of Public Health - Estados Unidos

Muestra la afiliación y género (detectado) para los co-autores de la publicación.

Financiamiento



Fuente
Universidad de Antioquia
National Institutes of Health
Spanish Ministry of Economy and Competitiveness
Ministry of Economy and Competitiveness
National Institute of Health
Ministerio de Economía y Competitividad
National Cancer Institute
National Institute of Allergy and Infectious Diseases
Bill and Melinda Gates Foundation
Ikerbasque, Basque Foundation for Science
Juergen Manchot Foundation
Aeras TB vaccine foundation and the Food and Drug Administration (FDA)
Billand Melinda Gates Foundation
National Institute of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID)
Alberta Glycomics Centre
Ikerbasque,Basque Foundation for Science
U.S. Food and Drug Administration
Aeras Global Tuberculosis Vaccine Foundation

Muestra la fuente de financiamiento declarada en la publicación.

Agradecimientos



Agradecimiento
This work was supported inpart by grants from the National Institute of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) AI105684 and AI096213-01 to JMA, the Aeras TB vaccine foundation and the Food and Drug Administration (FDA; 1U18FD004012/01 to JMA). RK acknowledges support from the Juergen Manchot Foundation. TLL, MJ and YB acknowledge support from Alberta Glycomics Centre and the Billand Melinda Gates Foundation. RP-R was supported in part by National Institutes of Health award 1R21AI115091. RPR is a 'Ramon y Cajal' fellow from the Spanish Ministry of Economy and Competitiveness. RPR acknowledge funding from the Ministry of Economy and Competitiveness SAF2016-77433-R. JA acknowledge support from the Ikerbasque, Basque Foundation for Science. The funders had no role in study design,data collection and analysis,decision to publish,or preparation of the manuscript
This work was supported in part by grants from the National Institute of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) AI105684 and AI096213-01 to JMA, the Aeras TB vaccine foundation and the Food and Drug Administration (FDA; 1U18 FD004012/01 to JMA). RK acknowledges support from the Juergen Manchot Foundation. TLL, MJ and YB acknowledge support from Alberta Glycomics Centre and the Bill and Melinda Gates Foundation. RP-R was supported in part by National Institutes of Health award 1R21AI115091. RPR is a ?Ramon y Cajal? fellow from the Spanish Ministry of Economy and Competitiveness. RPR acknowledge funding from the Ministry of Economy and Competitiveness SAF2016-77433-R. JA acknowledge support from the Ikerbasque, Basque Foundation for Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. AB acknowledges Estrategia de Sostenibilidad, Universidad de Antioquia.

Muestra la fuente de financiamiento declarada en la publicación.