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| 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
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.
| 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 |
| 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 EconomÃa 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 |
| 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. |