The zebrafish as a potential model for vaccine and adjuvant development.

Zebrafishesrepresent a proven model for human diseases and systems biology, exhibitingphysiological and genetic similarities and having innate and adaptive immunesystems. However, they are underexplored for human vaccinology, vaccinedevelopment, and testing. Here we summarize gaps and challenges. Zebrafish models have fourpotential applications: 1) Vaccine safety: The pastsuccesses in using zebrafishes to test xenobiotics could extend to vaccine andadjuvant formulations for general safety or target organs due to the zebrafish embryos'optical transparency. 2) Innate immunity: The zebrafish offers refined ways toexamine vaccine effects through signaling via Toll-like or NOD-like receptors inzebrafish myeloid cells. 3) Adaptive immunity: Zebrafishes produce IgM, IgD,and two IgZ immunoglobulins, but these are understudied, due to a lack of immunologicalreagents for challenge studies. 4) Systems vaccinology: Due to the availabilityof a well-referenced zebrafish genome, transcriptome, proteome, and epigenome,this model offers potential here. It remains unproven whether zebrafishes can beemployed for testing and developing human vaccines. We are still at thehypothesis-generating stage, although it is possible to begin outliningexperiments for this purpose. Throughtransgenic manipulation, zebrafish models could offer new paths for shapinganimal models and systems vaccinology.