Enhanced Control of Mycobacterium tuberculosis Extrapulmonary Dissemination in Mice by an Arabinomannan-Protein Conjugate Vaccine

Authors

R Prados-Rosales
L Carreno
T Cheng
C Blanc
B Weinrick
Aharona Glatman-Freedman, New York Medical CollegeFollow
A Casadevall
S Hung
A Tripathi
J Xu
Aharona Glatman-Freedman, New York Medical CollegeFollow
W Jacobs Jr.
J Chan
S Porcelli
J Achkar
A Casadevall

DOI

10.1371/journal.ppat.1006250

Journal Title

PLoS Pathogens

First Page

e1006250

Document Type

Article

Publication Date

3-9-2017

Department

Pediatrics

Keywords

Antigens, Bacterial, Mannans immunology, Mycobacterium tuberculosis immunology, Tuberculosis immunology, Tuberculosis Vaccines mmunology, Vaccines, Conjugate

Disciplines

Bacterial Infections and Mycoses | Bacteriology | Medicine and Health Sciences | Respiratory Tract Diseases

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.

Comments

Please see the work itself for the complete list of authors.

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.