Vaccination is one of the most effective control measure in preventing Streptococcus agalactiae infection. In this study, vaccine coatings were prepared with certain biomaterials such as chitosan, skim milk, and maltodextrin at concentration 1 % or 10 %, and further freeze-dried. Vaccine selected (in vitro) by tests: viability cell, solubility, protein concentration and protein molecular weight. The result of in vitro test showed that chitosan coating at doses 1 % and 10 % were the best in solubility and protein concentration test. Vaccine coated with chitosan was administrated again by injection (in vivo) in nile tilapia (Oreochromis niloticus) before challenged by S. agalactiae. This test consists of six treatments and three replications, i.e. the fish were injected with liquid vaccine (A), Phospat Buffered Saline (PBS) (B), vaccine with chitosan coating 1 % (C), vaccine with chitosan coating 10 % (D), chitosan 1 % (E), and chitosan 10 % (F). Parameters were observed including survival rate, relative percent survival (RPS), antibody titre, and total leucocyte. The results showed that treatment C showed a significant difference (P < 0,05) in survival rate 92.22 ± 3.85 %, RPS 85.21 ± 7.20 %, and antibody titre highest result, but not significant (P > 0,05) to increase total leukocyte in experimental fish against S. agalactiae infection. In conclusion, vaccine freeze dry with chitosan coated 1 % is effective to improve immunity system of nile tilapia.