دورية أكاديمية
A Mycobacterium ulcerans vaccine pilot trial using an accurate low-dose challenge.
| العنوان: | A Mycobacterium ulcerans vaccine pilot trial using an accurate low-dose challenge. |
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| المؤلفون: | Muhi S; Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Victoria, Australia.; Victorian Infectious Diseases Service, The Royal Melbourne Hospital, Parkville, Victoria, Australia., Porter JL; 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.; WHO Collaborating Centre for Mycobacterium ulcerans, Victorian Infectious Disease Reference Laboratory (VIDRL), Doherty Institute, Melbourne, Victoria, Australia. |
| المصدر: | Microbiology spectrum [Microbiol Spectr] 2024 Aug 06; Vol. 12 (8), pp. e0055524. Date of Electronic Publication: 2024 Jun 25. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: ASM Press Country of Publication: United States NLM ID: 101634614 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2165-0497 (Electronic) Linking ISSN: 21650497 NLM ISO Abbreviation: Microbiol Spectr Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : ASM Press, 2013- |
| مواضيع طبية MeSH: | Mice, Inbred BALB C* , Mycobacterium ulcerans*/immunology , Disease Models, Animal* , Buruli Ulcer*/immunology , Buruli Ulcer*/prevention & control , Buruli Ulcer*/microbiology , Bacterial Vaccines*/immunology , Bacterial Vaccines*/administration & dosage, Animals ; Mice ; Pilot Projects ; Female ; Humans ; Mycobacterium bovis/immunology ; Vaccination ; BCG Vaccine/immunology ; BCG Vaccine/administration & dosage |
| مستخلص: | A Mycobacterium ulcerans human challenge model has the potential to fundamentally advance our understanding of early human immune responses to infection, while rapidly evaluating vaccines and other therapeutic interventions. Here, using a murine tail infection model, we tested a very well-characterized working cell bank of the proposed challenge isolate M. ulcerans JKD8049 in naïve and Mycobacterium bovis bacille Calmette-Guérin (BCG)-vaccinated BALB/c mice. All 10 naïve mice were successfully infected with 20 colony-forming units (CFU) of M. ulcerans [95% confidence interval (CI) 17-22 CFU] with a mean time to visible lesion of 86 days (95% CI 79-92 days). In the 10 vaccinated mice, there was a significant delay in the mean time to lesion compared to the naïve controls of 24 days ( P = 0.0003), but all mice eventually developed ulcerative lesions. This study informs a future human infection model by demonstrating the successful application of the challenge agent in this in vivo model and highlights both the promise and the problems with trying to induce protective immunity against M. ulcerans . Importance: In preparation for its proposed use in a controlled human infection model (CHIM), this study reports the successful infection of BALB/c mice using a carefully characterized, low-dose inoculum of Mycobacterium ulcerans JKD8049 (our proposed CHIM strain). We also demonstrate that Mycobacterium bovis bacille Calmette-Guérin delays the onset of disease but cannot alter the course of illness once a lesion becomes apparent. We also validate the findings of previous low-dose challenges that used less accurate methods to determine the inoculum, but our presented methodology is practical, accurate, and anticipated to be reproducible. Competing Interests: The authors declare no conflict of interest. |
| معلومات مُعتمدة: | GNT1191368 DHAC | National Health and Medical Research Council (NHMRC); GNT1194325 DHAC | National Health and Medical Research Council (NHMRC) |
| فهرسة مساهمة: | Keywords: Buruli ulcer; M. bovis BCG; Mycobacterium ulcerans; challenge; infection model; murine; vaccine |
| المشرفين على المادة: | 0 (Bacterial Vaccines) 0 (BCG Vaccine) |
| تواريخ الأحداث: | Date Created: 20240625 Date Completed: 20240808 Latest Revision: 20240808 |
| رمز التحديث: | 20240808 |
| مُعرف محوري في PubMed: | PMC11302252 |
| DOI: | 10.1128/spectrum.00555-24 |
| PMID: | 38916323 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2165-0497 |
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| DOI: | 10.1128/spectrum.00555-24 |