Enhanced control of Mycobacterium tuberculosis extrapulmonary dissemination in mice by an arabinomannan-protein conjugate vaccine

Rafael Prados-Rosales, Leandro Carreño, Tingting Cheng, Caroline Blanc, Brian Weinrick, Adel Malek, Todd L. Lowary, Andres Baena, Maju Joe, Yu Bai, Rainer Kalscheuer, Ana Batista-Gonzalez, Noemi A. Saavedra, Leticia Sampedro, Julen Tomás, Juan Anguita, Shang Cheng Hung, Ashish Tripathi, Jiayong Xu, Aharona Glatman-FreedmanWilliams R. Jacobs, John Chan, Steven A. Porcelli, Jacqueline M. Achkar, Arturo Casadevall

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbere1006250
JournalPLoS pathogens
Volume13
Issue number3
DOIs
StatePublished - Mar 2017

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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