RT Journal Article T1 BEI Inactivated Vaccine Induces Innate and Adaptive Responses and Elicits Partial Protection upon Reassortant Betanodavirus Infection in Senegalese Sole A1 Valero Cuesta, Yulema A1 Olveira Hermida, José Gabriel A1 López Vázquez, Carmen A1 Pereira Dopazo, Carlos A1 Bandín Matos, Isabel K1 Senegalese sole K1 Inactivated vaccine K1 BEI K1 Formalin K1 Nervous necrosis virus K1 Immune response K1 Antibodies K1 Gene expression AB Nervous necrosis virus (NNV), the causative agent of viral encephalopathy and retinopathy (VER), is one of the most threatening viruses affecting marine and freshwater fish species worldwide. Senegalese sole is a promising fish species in Mediterranean aquaculture but also highly susceptible to NNV and VER outbreaks, that puts its farming at risk. The development of vaccines for aquaculture is one of best tools to prevent viral spread and sudden outbreaks, and virus inactivation is the simplest and most cost-effective method available. In this work, we have designed two inactivated vaccines based on the use of formalin or binary ethylenimine (BEI) to inactivate a reassortant NNV strain. After vaccination, the BEI-inactivated vaccine triggered the production of specific IgM-NNV antibodies and stimulated innate and adaptive immune responses at transcriptional level (rtp3, mx, mhcii and tcrb coding genes). Moreover, it partially improved survival after an NNV in vivo challenge, reducing the mid-term viral load and avoiding the down-regulation of immune response post-challenge. On the other hand, the formalin-inactivated vaccine improved the survival of fish upon infection without inducing the production of IgM-NNV antibodies and only stimulating the expression of herc4 and mhcii genes (in head-kidney and brain, respectively) during the vaccination period; this suggests that other immune-related pathways may be involved in the partial protection provoked. Although these vaccines against NNV showed encouraging results, further studies are needed to improve sole protection and to fully understand the underlying immune mechanism PB MDPI YR 2021 FD 2021 LK http://hdl.handle.net/10347/26398 UL http://hdl.handle.net/10347/26398 LA eng NO Vaccines 2021, 9(5), 458; https://doi.org/10.3390/vaccines9050458 NO This work was supported by grant RTI2018-094687-B-C21 from MICIU (Spain) co-funded by FEDER DS Minerva RD 28 abr 2026