title: DNA vaccination boosts Bacillus Calmette-Guérin protection against mycobacterial infection in zebrafish.
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.
authors.affiliation: BioMediTech, University of Tampere, FIN 33014, Tampere, Finland.
authors.forename: Kaisa E
authors.initials: KE
authors.lastname: Oksanen
authors.affiliation: BioMediTech, University of Tampere, FIN 33014, Tampere, Finland.
authors.forename: Henna
authors.initials: H
authors.lastname: Myllymäki
authors.affiliation: BioMediTech, University of Tampere, FIN 33014, Tampere, Finland.
authors.forename: Maarit J
authors.initials: MJ
authors.lastname: Ahava
authors.affiliation: BioMediTech, University of Tampere, FIN 33014, Tampere, Finland.
authors.forename: Leena
authors.initials: L
authors.lastname: Mäkinen
authors.affiliation: BioMediTech, University of Tampere, FIN 33014, Tampere, Finland.
authors.forename: Mataleena
authors.initials: M
authors.lastname: Parikka
authors.affiliation: BioMediTech, University of Tampere, FIN 33014, Tampere, Finland; Department of Pediatrics, Tampere University Hospital, FIN 33521, Tampere, Finland; Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland; PEDEGO Research Unit, and Medical Research Center Oulu, University of Oulu, Oulu, Finland. Electronic address: mika.ramet@uta.fi.
authors.forename: Mika
authors.initials: M
authors.lastname: Rämet
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000276:immunology*; D004195:Disease Models, Animal; D009165:Mycobacterium Infections, Nontuberculous / Q000517:prevention & control*; D019910:Mycobacterium marinum; D016133:Polymerase Chain Reaction; D019444:Vaccines, DNA / Q000276:immunology*; D015027:Zebrafish
chemical_list: D001500:BCG Vaccine; D019444:Vaccines, DNA
keywords: BCG; Mycobacterium marinum; Tuberculosis; Vaccine; Zebrafish