Long-term protective efficacy and distinct immune responses of live and inactivated vaccines against cryptocaryoniasis in orange-spotted grouper (Epinephelus coioides).

Cryptocaryoniasis remains a major constraint in marine aquaculture, and vaccination represents a promising strategy for its control. However, the immune mechanisms underlying the distinct protective efficacies of live and inactivated vaccines against Cryptocaryon irritans remain insufficiently defined. In this study, we compared long-term protection and host immune responses induced by live and inactivated vaccines in Epinephelus coioides. The live vaccine conferred durable protection for at least 20 weeks, whereas the inactivated vaccine only demonstrated measurable efficacy at 12 weeks. Although parasite loads were similar among groups within the first 24 h post-challenge, only live-vaccinated fish exhibited a rapid reduction in parasite abundance within 24-48 h, which coincided with elevated mucosal IgM levels. Transcriptomic profiling further revealed that the live vaccine was associated with a coordinated immune program characterized by early mucosal antibody activation and sustained innate effector responses, whereas the inactivated vaccine predominantly induced transient inflammatory signaling with limited adaptive engagement. Collectively, these findings elucidate the divergent immune mechanisms elicited by live and inactivated vaccines, offering a theoretical framework for the rational design of effective vaccines against cryptocaryoniasis.