PUBLICATION

DNA Vaccination Boosts Bacillus Calmette-Guérin Protection against Mycobacterial Infection in Zebrafish

Authors
Oksanen, K.E., Myllymäki, H., Ahava, M.J., Mäkinen, L., Parikka, M., Rämet, M.
ID
ZDB-PUB-150913-2
Date
2016
Source
Developmental and comparative immunology   54(1): 89-96 (Journal)
Registered Authors
Keywords
BCG, Mycobacterium marinum, tuberculosis, vaccine, zebrafish
MeSH Terms
  • Animals
  • BCG Vaccine/immunology*
  • Disease Models, Animal
  • Mycobacterium Infections, Nontuberculous/prevention & control*
  • Mycobacterium marinum
  • Polymerase Chain Reaction
  • Vaccines, DNA/immunology*
  • Zebrafish
PubMed
26363085 Full text @ Dev. Comp. Immunol.
Abstract
Despite the widespread use of the current Bacillus Calmette-Guérin (BCG) vaccine, tuberculosis is still a major cause of morbidity and mortality worldwide. Vaccination with BCG does not prevent a Mycobacterium tuberculosis infection, nor does it inhibit the reactivation of latent tuberculosis. Here, we show that adult zebrafish are modestly and variably protected from a mycobacterial infection by BCG vaccination. An intraperitoneal (i.p.) BCG vaccination was associated with enhanced survival upon a high-dose (20,000 bacteria) Mycobacterium marinum infection. In addition, BCG-vaccinated fish were more able to restrict a low-dose (30 bacteria) intraperitoneal infection with M. marinum, as indicated by lower bacterial loads at six weeks post infection (wpi). However, the vaccination could not completely prevent an infection. A qRT-PCR analysis comparing BCG-vaccinated and unvaccinated fish upon a mycobacterial infection indicated that the induction of Tumor necrosis factor (TNF) was more modest in vaccinated fish. The partial protection gained by BCG could be boosted by a DNA vaccine combining Ag85B, ESAT6 and a resuscitation-related gene RpfE, suggesting that this combination of antigens could be useful for a future BCG booster vaccine. We conclude that zebrafish is a useful early-phase preclinical model for studying subunit vaccines designed for boosting the effects of BCG.
Genes / Markers
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping