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Enhanced control of Mycobacterium tuberculosis extrapulmonary dissemination in mice by an arabinomannan-protein conjugate vaccine
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نویسنده
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prados-rosales r. ,carreño l. ,cheng t. ,blanc c. ,weinrick b. ,malek a. ,lowary t.l. ,baena a. ,joe m. ,bai y. ,kalscheuer r. ,batista-gonzalez a. ,saavedra n.a. ,sampedro l. ,tomás j. ,anguita j. ,hung s.-c. ,tripathi a. ,xu j. ,glatman-freedman a. ,jacobs w.r. ,chan j. ,porcelli s.a. ,achkar j.m. ,casadevall a.
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منبع
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plos pathogens - 2017 - دوره : 13 - شماره : 3
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چکیده
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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. © 2017 prados-rosales et al.
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آدرس
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department of microbiology and immunology,albert einstein college of medicine,bronx,ny,united states,cic biogune,bizkaia technology park,derio,bizkaia, Spain, department of microbiology and immunology,albert einstein college of medicine,bronx,ny,united states,millennium institute on immunology and immunotherapy,programa disciplinario de inmunologia,facultad de medicina,universidad de chile,santiago, Chile, department of microbiology and immunology,albert einstein college of medicine,bronx,ny,united states,department of medicine,albert einstein college of medicine,bronx,ny, United States, department of microbiology and immunology,albert einstein college of medicine,bronx,ny,united states,department of medicine,albert einstein college of medicine,bronx,ny, United States, department of microbiology and immunology,albert einstein college of medicine,bronx,ny,united states,howard hughes medical institute,albert einstein college of medicine,bronx,ny, United States, department of microbiology and immunology,albert einstein college of medicine,bronx,ny,united states,howard hughes medical institute,albert einstein college of medicine,bronx,ny, United States, alberta glycomics centre and department of chemistry,university of alberta,gunning-lemieux chemistry center,edmonton,ab, Canada, grupo de inmunologia celular e inmunogenetica,universidad de antioquia,medellin, Colombia, alberta glycomics centre and department of chemistry,university of alberta,gunning-lemieux chemistry center,edmonton,ab, Canada, alberta glycomics centre and department of chemistry,university of alberta,gunning-lemieux chemistry center,edmonton,ab, Canada, institute for medical microbiology and hospital hygiene,heinrich-heine-university duesseldorf,duesseldorf, Germany, department of microbiology and immunology,albert einstein college of medicine,bronx,ny, United States, department of microbiology and immunology,albert einstein college of medicine,bronx,ny, United States, cic biogune,bizkaia technology park,derio,bizkaia, Spain, cic biogune,bizkaia technology park,derio,bizkaia, Spain, cic biogune,bizkaia technology park,derio,bizkaia,spain,ikerbasque,basque foundation for science,bilbao,bizkaia, Spain, genomics research center,academia sinica,section 2,nankang,taipei, Taiwan, genomics research center,academia sinica,section 2,nankang,taipei, Taiwan, department of microbiology and immunology,albert einstein college of medicine,bronx,ny,united states,department of medicine,albert einstein college of medicine,bronx,ny, United States, infectious diseases unit center for disease control ministry of health,tel hashomer,israel,department of pediatrics,and department of family and community medicine,new york medical college,valhalla,ny, United States, jr.,department of microbiology and immunology,albert einstein college of medicine,bronx,ny,united states,howard hughes medical institute,albert einstein college of medicine,bronx,ny, United States, department of microbiology and immunology,albert einstein college of medicine,bronx,ny,united states,department of medicine,albert einstein college of medicine,bronx,ny, United States, department of microbiology and immunology,albert einstein college of medicine,bronx,ny, United States, department of microbiology and immunology,albert einstein college of medicine,bronx,ny,united states,department of medicine,albert einstein college of medicine,bronx,ny, United States, department of microbiology and immunology,albert einstein college of medicine,bronx,ny,united states,department of molecular microbiology and immunology,johns hopkins bloomberg school of public health,baltimore,md, United States
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Authors
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