Application of Biomimetic Cell-Derived Nanoparticles with Mannose Modification as a Novel Vaccine Delivery Platform against Teleost Fish Viral Disease.

Although cell membrane-coated nanoparticles are widely used as a promising nanodelivery platform, a few studies reported their application in developing the teleost nanovaccine delivery system. Here, we present a biomimetic vaccine delivery platform by encapsulating chitosan-loaded DNA vaccine with teleost erythrocytes membrane modified by mannose. The developed CS-G@M-M nanovaccine delivery platform shows good biocompatibility in vivo and in vitro. With further modification of mannose moiety, the constructed CS-G@M-M showed enhanced uptake by antigen-presenting cells (APCs) and increased accumulation of CS-G@M-M in immune tissues including spleen, kidney, and hindgut. Critically, using a quantitative real-time polymerase chain reaction (qRT-PCR) assay, increased mRNA levels of immune-related genes were detected in spleen and hindgut of vaccinated fish. Moreover, through enzyme-linked immunosorbent assay (ELISA), we found that the levels of CD80/86, TNF-α, IgM, and IgZ in spleen and hindgut were significantly increased. To evaluate the immunoprotection efficacy of the constructed nanovaccine, spring viremia of carp virus (SVCV), a rhabdovirus of worldwide importance that requires notification within 48 h to the International Office of Epizootics once detected, was used as a model for virus challenge. We carried out three challenge tests on 3rd, 21st, and 70th days post vaccination, respectively. Notably, CS-G@M-M nanovaccine showed durability of immunoprotection efficacy that could protect zebrafish from SVCV challenge. This work presents a novel design of smart teleost erythrocytes membrane-coated nanoparticles, which are inherently biocompatible, promising for eliciting robust adaptive immune responses in preventing fish viral diseases.