NYMC Faculty Publications
DOI
10.1371/journal.ppat.1006250
Journal Title
PLoS Pathogens
First Page
e1006250
Document Type
Article
Publication Date
3-9-2017
Department
Pediatrics
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.
Recommended Citation
Prados-Rosales, R., Carreno, L., Cheng, T., Blanc, C., Weinrick, B., Glatman-Freedman, A., Casadevall, A., Hung, S., Tripathi, A., Xu, J., Glatman-Freedman, A., Jacobs Jr., W., Chan, J., Porcelli, S., Achkar, J., & Casadevall, A. (2017). Enhanced Control of Mycobacterium tuberculosis Extrapulmonary Dissemination in Mice by an Arabinomannan-Protein Conjugate Vaccine. PLoS Pathogens, 13 (3), e1006250. https://doi.org/10.1371/journal.ppat.1006250
Publisher's Statement
Originally published in PLoS Pathogens 13(3): e1006250. The original material can be found here.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Included in
Bacterial Infections and Mycoses Commons, Bacteriology Commons, Respiratory Tract Diseases Commons
Comments
Please see the work itself for the complete list of authors.