Mucosal delivery of mannose functionalized biomimetic nanoparticles via the branchial route induces robust mucosal and systemic immune responses against fish viral disease

Most infectious agents affect or start from a mucosal surface, therefore mucosal immunization would be expected to be a promising method to efficiently induce local and systemic immunity against these infections. Since fish gill is a mucosal surface containing organized lymphoid structure, which is considered as a potential site for vaccination. Herein, we designed a novel biomimetic nanovaccine by encapsulating poly(D,l-lactide-co-glycolide)-based DNA vaccine with teleost erythrocytes membrane modified by mannose. Since all the materials used for the construction of PG@EM-M nanovaccine are fully biocompatible, PG@EM-M shown good biocompatibility in vivo and in vitro. Zebrafish, a model organism, were immunized with PG@EM-M nanovaccine via branchial route to evaluate the local and systemic immunity. As an environmentally and economically important rhabdovirus, spring viremia of carp virus (SVCV) was used as a model for virus challenge. Three SVCV challenge tests were carried out in zebrafish on 7th, 28th, and 70th day post vaccination, respectively. PG@EM-M vaccinated fish shown highest survival rate of ca.48%, ca.81%, and ca.62% on 7th, 28th, and 70th day post vaccination, respectively. In addition, the viral loads were significantly decreased (P < 0.01) in gill and spleen tissues after PG@EM-M vaccination, respectively. Owing to the specific interaction between mannose moiety with antigen presenting cells (APCs), as expected, PG@EM-M shown significantly enhanced of cellular uptake by APCs compared to PG@EM (without mannose modification). Interestingly, we found strong retention ability of PG@EM-M in the local immunization site (gill), and its migration to systemic immune tissues (spleen). Notably, this study demonstrated that PG@EM-M could induce robust mucosal and systemic immune response in vaccinated fish via the branchial route. This work presents a novel design of erythrocytes-mimic nanoparticles for mucosal immunization, which would be expected to increase the efficacy and improve the design of mucosal vaccines for aquaculture.