Streptococcus iniae (SI) causes a fatal meningoencephalitis in commercially important fish species, including striped bass, tilapia and salmon. The lead investigator has identified several SI genes required for fish virulence and has subsequently developed a preliminary vaccine that uses live attenuated mutants. In the second year of this project, the scientist will continue to develop this vaccine, working closely with a commercial seabass farm. Some specific aims: to finish virulence gene characterization in the full panel of attenuated mutants; to use directed mutagenesis to delete key virulence genes; and, to conduct large-scale vaccination trials with selected deletion mutants. The U.S. aquaculture industry stands to benefit greatly if a cost-effective, commercially available vaccine can be developed.