Divergent B-cell repertoire remodelling by mRNA, DNA and live attenuated vaccines in fish

Vaccination is critical for the future of aquaculture, and nucleic acid vaccines have a major potential for fighting emerging fish infectious diseases, yet their mechanisms remain poorly understood. We compared B-cell responses induced by an mRNA, a DNA, and an attenuated vaccine, all encoding the same antigen against a fish rhabdovirus. Rainbow trout IgHμ repertoires were examined to investigate how vaccines reshape clonal composition and complexity of the B-cell repertoire. The attenuated virus drove protection through a small number of highly shared public clonotypes encoding neutralizing antibodies. The mRNA vaccine profoundly remodelled the repertoire in some individuals and induces low, but still protective, neutralising Ab titers without public expansions. The DNA vaccine induced high neutralizing Ab titers, providing full protection with minimal impact on B-cell repertoire. Clustering analysis revealed partial sharing of private responses between fish. These findings highlight profound divergences between fish B-cell responses to nucleic acid and attenuated vaccines whilst all of three vaccines induce protective responses.