- Streptococcus suis causes swine streptococcosis which frequently results in fatality of the infected newborn and weaning piglets; thus it has great negative impact, not only on the backyard pig rearing, but also the livestock development and the swine industry. The bacteria often mediate interspecies transmission to infect humans causing sepsis, meningitis, endocarditis, severe arthritis, and septic shock with high case mortality rate or, to the minimum, irreversible deafness among the survivors. This anthropozoonosis has become one of the major concerns of the public health authority in Thailand as the incidence has been increasing since 2001, especially in the northern region. S. suis infection is conventionally diagnosed by using microbiological method, i.e., laboratory culture and biochemical identification of the bacteria in patient’s samples such as blood. S. suis, however, is difficult to distinguish from other streptococci which confounds interpretation of the laboratory result. Currently, no vaccine is as yet available for both veterinary and human use. Vaccine development faces several obstacles including the lack of knowledge on the bacterial virulence factors and pathogenic mechanisms, patho-physiology of the host, as well as the host immune correlate of protection. Thus, a search for the bacterial diagnostic marker and vaccine candidate is a perceived necessity in combating this deadly disease. In this study, a gel based-two dimensional (2-DE)-proteomics was used to identify the in vivo expressed antigens of S. sius that induced antibody response in all contracted humans and pigs. Immunome, i.e., whole repertoire of immunogenic components, of S. suis was also 6 studied by using immune sera of mice immunized with S. suis whole cell homogenate in 2-DE-immunoblotting. It was found that the common in vivo expressed antigens of S. suis that were immunogenic in all three species (pig, human and mouse) were: 2- nitropropane dioxygenase (pI 4.8, MW 84 kDa), stress response protein, arginine deiminase (pI 5.2, MW 50 kDa) and uridylate kinase (pI 4.2, MW 27 kDa). Among the three proteins, arginine deiminase appeared to have a presumptive role in the bacterial pathogenicity. All strains of S. suis isolated from contracted humans and pigs were positive by PCR for arginine deiminase coding sequence. Recombinant arginine deiminase of S. suis was produced. BALB/c mice (four weeks old) were immunized subcutaneously with two doses of the protein mixed with alum at 14 day interval. Control mice received PBS mixed with the adjuvant. Serum antibodies from the vaccine incitement were predominantly IgM and IgG1 indicating satisfactory Th2 response. Immunized mice challenged with S. suis showed significant reduction of bacterial recovery from blood, brain, liver, spleen and thoracic-abdominal serosa when compared to those from samples of the placebo-immunized counterparts. Reduction in morbidity and mortality rates were also observed. Mitigation of severity of histopathological features in vaccinated mice in comparison to the mocks will be investigated further. This study has elucidated potential of S. suis arginine deiminase as a diagnostic marker and vaccine candidate for S. sius infection in both natural host species, i.e., swine and human.