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

PeerJ

article

Kirstie M. Mangas¹  Nicholas J. Tobias²  Estelle Marion⁴  Jérémie Babonneau⁴  Laurent Marsollier⁴  Jessica L. Porter¹  Sacha J. Pidot¹  Chinn Yi Wong¹  David C. Jackson¹  Brendon Y. Chua¹  Timothy P. Stinear¹ 

[1] Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne;Johann Wolfgang Goethe Universität Frankfurt am Main;LOEWE Centre for Translational Biodiversity in Genomics;Université de Nantes;Université d’Angers

关键词: Mycobacterium ulcerans;    Buruli ulcer;    Vaccination;    Mycobacterium;    Subunit vaccine;    ELISA;    Antibody;   

DOI  :  10.7717/peerj.9659

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundMycobacterium 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.MethodsRecombinant 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.ResultsThe MUL_3720 and Hsp18 vaccines induced high titres of antigen-specific antibodies that were predominately subtype IgG1. 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.ConclusionsThese 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.

【 授权许可】

CC BY