University of Oulu

Myllymäki H, Niskanen M, Oksanen KE, Sherwood E, Ahava M, Parikka M, et al. (2017) Identification of novel antigen candidates for a tuberculosis vaccine in the adult zebrafish (Danio rerio). PLoS ONE 12(7): e0181942.

Identification of novel antigen candidates for a tuberculosis vaccine in the adult zebrafish (Danio rerio)

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Author: Myllymäki, Henna1; Niskanen, Mirja1; Oksanen, Kaisa Ester1;
Organizations: 1BioMediTech Institute and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
2Oral and Maxillofacial Unit, Tampere University Hospital, Tampere , Finland
3PEDEGO Research Unit, Medical Research Center Oulu, University of Oulu, Oulu, Finland , and Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 6.2 MB)
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Language: English
Published: Public Library of Science, 2017
Publish Date: 2019-09-13


Tuberculosis (TB) remains a major global health challenge and the development of a better vaccine takes center stage in fighting the disease. For this purpose, animal models that are capable of replicating the course of the disease and are suitable for the early-stage screening of vaccine candidates are needed. A Mycobacterium marinum infection in adult zebrafish resembles human TB. Here, we present a pre-clinical screen for a DNA-based tuberculosis vaccine in the adult zebrafish using an M. marinum infection model. We tested 15 antigens representing different types of mycobacterial proteins, including the Resuscitation Promoting factors (Rpf), PE/PPE protein family members, other membrane proteins and metabolic enzymes. The antigens were expressed as GFP fusion proteins, facilitating the validation of their expression in vivo. The efficiency of the antigens was tested against a low-dose intraperitoneal M. marinum infection (≈ 40 colony forming units), which mimics a primary M. tuberculosis infection. While none of the antigens was able to completely prevent a mycobacterial infection, four of them, namely RpfE, PE5_1, PE31 and cdh, led to significantly reduced bacterial burdens at four weeks post infection. Immunization with RpfE also improved the survival of the fish against a high-dose intraperitoneal injection with M. marinum (≈ 10.000 colony forming units), resembling the disseminated form of the disease. This study shows that the M. marinum infection model in adult zebrafish is suitable for the pre-clinical screening of tuberculosis vaccines and presents RpfE as a potential antigen candidate for further studies.

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Series: PLoS one
ISSN: 1932-6203
ISSN-E: 1932-6203
ISSN-L: 1932-6203
Volume: 12
Issue: 7
Article number: e0181942
DOI: 10.1371/journal.pone.0181942
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Funding: This work was supported by: the Tampere Tuberculosis Foundation,, (HM, KEO, MP and MR); the Finnish Academy (MR) (grant number 277495),; the Sigrid Juselius Foundation,, (MR, MP); the Jane and Aatos Erkko Foundation,, (MR); the Competitive State Research Financing of the Expert Responsibility Area of Tampere University Hospital,, (MR); -Competitive State Research Financing of the Expert Responsibility area of Oulu University Hospital,, (MR); the Finnish Anti-tuberculosis Foundation,, (HM, KEO, MP); the Finnish Cultural Foundation Pirkanmaa Regional Fund,, (KEO).
Copyright information: © 2017 Myllymäki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.