High antibody titres induced by protein subunit vaccines using Mycobacterium ulcerans antigens Hsp18 and MUL_3720 with a TLR-2 agonist fail to protect against Buruli ulcer in mice.

Autor: Mangas KM; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia., Tobias NJ; Johann Wolfgang Goethe Universität Frankfurt am Main, Frankfurt, Germany.; LOEWE Centre for Translational Biodiversity in Genomics (TBG), Frankfurt, Germany., Marion E; Université de Nantes, Nantes, France.; Université de Nantes, Nantes, France.; Université d'Angers, Angers, France., Babonneau J; Université de Nantes, Nantes, France.; Université d'Angers, Angers, France., Marsollier L; Université de Nantes, Nantes, France.; Université d'Angers, Angers, France., Porter JL; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia., Pidot SJ; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia., Wong CY; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia., Jackson DC; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia., Chua BY; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia., Stinear TP; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.
Jazyk: angličtina
Zdroj: PeerJ [PeerJ] 2020 Aug 07; Vol. 8, pp. e9659. Date of Electronic Publication: 2020 Aug 07 (Print Publication: 2020).
DOI: 10.7717/peerj.9659
Abstrakt: Background: Mycobacterium ulcerans is the causative agent of a debilitating skin and soft tissue infection known as Buruli ulcer (BU). There is no vaccine against BU. The purpose of this study was to investigate the vaccine potential of two previously described immunogenic M. ulcerans proteins, MUL_3720 and Hsp18, using a mouse tail infection model of BU.
Methods: Recombinant versions of the two proteins were each electrostatically coupled with a previously described lipopeptide adjuvant. Seven C57BL/6 and seven BALB/c mice were vaccinated and boosted with each of the formulations. Vaccinated mice were then challenged with M. ulcerans via subcutaneous tail inoculation. Vaccine performance was assessed by time-to-ulceration compared to unvaccinated mice.
Results: The MUL_3720 and Hsp18 vaccines induced high titres of antigen-specific antibodies that were predominately subtype IgG 1 . However, all mice developed ulcers by day-40 post- M. ulcerans challenge. No significant difference was observed in the time-to-onset of ulceration between the experimental vaccine groups and unvaccinated animals.
Conclusions: These data align with previous vaccine experiments using Hsp18 and MUL_3720 that indicated these proteins may not be appropriate vaccine antigens. This work highlights the need to explore alternative vaccine targets and different approaches to understand the role antibodies might play in controlling BU .
Competing Interests: Timothy Stinear is an Academic Editor for PeerJ.
(©2020 Mangas et al.)
Databáze: MEDLINE
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