PUBLICATION
Identification of novel antigen candidates for a tuberculosis vaccine in the adult zebrafish (Danio rerio)
- Authors
- Myllymäki, H., Niskanen, M., Oksanen, K.E., Sherwood, E., Ahava, M., Parikka, M., Rämet, M.
- ID
- ZDB-PUB-170726-3
- Date
- 2017
- Source
- PLoS One 12: e0181942 (Journal)
- Registered Authors
- Keywords
- Mycobacterium tuberculosis, Vaccines, Tuberculosis, Zebrafish, DNA vaccination, Fluorescence microscopy, Membrane proteins, Enzyme-linked immununoassays
- MeSH Terms
-
- Animals
- Antigens, Bacterial/immunology*
- Antigens, Bacterial/therapeutic use
- Disease Models, Animal
- Fish Diseases/immunology
- Fish Diseases/microbiology
- Fish Diseases/prevention & control*
- Mycobacterium Infections, Nontuberculous/immunology
- Mycobacterium Infections, Nontuberculous/prevention & control*
- Mycobacterium Infections, Nontuberculous/veterinary
- Mycobacterium marinum/immunology*
- Tuberculosis Vaccines/therapeutic use*
- Zebrafish/immunology
- Zebrafish/microbiology
- PubMed
- 28742838 Full text @ PLoS One
Citation
Myllymäki, H., Niskanen, M., Oksanen, K.E., Sherwood, E., Ahava, M., Parikka, M., Rämet, M. (2017) Identification of novel antigen candidates for a tuberculosis vaccine in the adult zebrafish (Danio rerio). PLoS One. 12:e0181942.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping