Immunoregulation mediated by the enzyme inhibitory activity of helminth-derived serine protease inhibitor affects the protective efficiency of vaccines

Recently, the prevalence of trichinellosis has increased the threat to animal food safety and public health worldwide. Pathogen-derived proteins are potential vaccine candidates for preventing and controlling <i>Trichinella spiralis</i> (<i>T. spiralis</i>) infection. However, the effect of protein-induced immunoregulation on vaccine protection remains unclear. In this study, a secretory protein derived from <i>T. spiralis</i> (<i>Ts</i>-serpin), whose enzyme inhibitory activity interfered with the host enzymatic reaction, was selected to reveal the way in which enzyme inhibitory activity regulates the immune system and its impact on the protective efficiency of vaccines. By modifying <i>Ts</i>-serpin, mutant proteins not only reduce the enzyme inhibition activity of <i>Ts</i>-serpin but also enhance the protective effect of vaccines in female BALB/c mice. The preference of mutant proteins for the inhibition on chymotrypsin and elastase affects different types of immune cells. In summary, the diverse inhibitory effects of <i>Ts</i>-serpin on serine proteases were shown to reduce the protective effects of active immunity by regulating the immune system. Our research provides an important basis for modifying protease inhibitors as vaccines to prevent infectious diseases and provides evidence for pathogenic invasion by interfering with host protease-related activity.