Designing Selenium Nanoadjuvant as Universal Agent for Live‐Killed Virus‐Based Vaccine

Abstract Inactivated virus vaccines with whole antigen spectra and good safety are the commonly used modality for preventing infections. However, the poor immunogenicity greatly limits its clinical applications. Herein, by taking advantages of the crucial roles of Se in the functions of immune cells and its biomineralization property, it successfully in‐situ synthesized Se nanoadjuvant on inactivated viruses such as porcine epidemic diarrhea virus (PEDV), pseudorabies virus (PRV), and porcine reproductive and respiratory syndrome virus (PRRSV) in a facile method, which is universal to construct other inactivated virus vaccines. The nanovaccine can highly effectively enhance the uptake of PEDV/PRV/PRRSV into dendritic cells (DCs) and activate DCs via triggering TLR4 signaling pathways and regulating selenoproteins expressions. Furthermore, it exhibited better activities in triggering macrophages and natural killer cells‐mediated innate immunity and T cells‐mediated cellular immunity compared to PEDV and the commercial inactivated PEDV vaccine on both mice and swine models. This study provides a universal Se nanoadjuvant for developing inactivated viruses‐based nanovaccines for preventing virus infections.