Vaccine-Specific Immune Responses against Mycobacterium ulcerans Infection in a Low-Dose Murine Challenge Model.

Autor: Mangas KM; Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Victoria, Australia., Buultjens AH; Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Victoria, Australia., Porter JL; Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Victoria, Australia., Baines SL; Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Victoria, Australia., Marion E; CRCINA, INSERM, Université de Nantes, Université d'Angers, Angers, France., Marsollier L; CRCINA, INSERM, Université de Nantes, Université d'Angers, Angers, France., Tobias NJ; Molekulare Biotechnologie, Fachbereich Biowissenschaften, Goethe-Universität Frankfurt, Frankfurt am Main, Germany.; LOEWE Centre for Translational Biodiversity in Genomics (TBG), Frankfurt am Main, Germany., Pidot SJ; Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Victoria, Australia., Quinn KM; Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia., Price DJ; Victorian Infectious Diseases Reference Laboratory Epidemiology Unit at The Peter Doherty Institute for Infection & Immunity, The University of Melbourne and Royal Melbourne Hospital, Parkville, Victoria, Australia.; Centre for Epidemiology & Biostatistics, Melbourne School of Population & Global Health, The University of Melbourne, Melbourne, Victoria, Australia., Kedzierska K; Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Victoria, Australia., Zeng W; Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Victoria, Australia., Jackson DC; Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Victoria, Australia., Chua BY; Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Victoria, Australia., Stinear TP; Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Victoria, Australia tstinear@unimelb.edu.au.
Jazyk: angličtina
Zdroj: Infection and immunity [Infect Immun] 2020 Feb 20; Vol. 88 (3). Date of Electronic Publication: 2020 Feb 20 (Print Publication: 2020).
DOI: 10.1128/IAI.00753-19
Abstrakt: The neglected tropical disease Buruli ulcer (BU) is an infection of subcutaneous tissue with Mycobacterium ulcerans There is no effective vaccine. Here, we assessed an experimental prime-boost vaccine in a low-dose murine tail infection model. We used the enoyl reductase (ER) domain of the M. ulcerans mycolactone polyketide synthases electrostatically coupled with a previously described Toll-like receptor 2 (TLR-2) agonist-based lipopeptide adjuvant, R 4 Pam 2 Cys. Mice were vaccinated and then challenged via tail inoculation with 14 to 20 CFU of a bioluminescent strain of M. ulcerans Mice receiving either the experimental ER vaccine or Mycobacterium bovis bacillus Calmette-Guérin (BCG) were equally protected, with both groups faring significantly better than nonvaccinated animals ( P <  0.05). To explore potential correlates of protection, a suite of 29 immune parameters were assessed in the mice at the end of the experimental period. Multivariate statistical approaches were used to interrogate the immune response data to develop disease-prognostic models. High levels of interleukin 2 (IL-2) and low gamma interferon (IFN-γ) produced in the spleen best predicted control of infection across all vaccine groups. Univariate logistic regression revealed vaccine-specific profiles of protection. High titers of ER-specific IgG serum antibodies together with IL-2 and IL-4 in the draining lymph node (DLN) were associated with protection induced by the ER vaccine. In contrast, high titers of IL-6, tumor necrosis factor alpha (TNF-α), IFN-γ, and IL-10 in the DLN and low IFN-γ titers in the spleen were associated with protection following BCG vaccination. This study suggests that an effective BU vaccine must induce localized, tissue-specific immune profiles with controlled inflammatory responses at the site of infection.
(Copyright © 2020 American Society for Microbiology.)
Databáze: MEDLINE
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