Vinh N.T.Dong H.T.Turner J.K.Senapin S.Turner W.A.Mahidol University2026-03-162026-03-162026-01-01Frontiers in Veterinary Science Vol.13 (2026)https://repository.li.mahidol.ac.th/handle/123456789/115734While novel and advanced vaccine technologies offer significant potential for aquaculture, their adoption is often limited by high costs, particularly in low-value species like tilapia, underscoring the value of simpler approaches. Streptococcus agalactiae is a major pathogen in tilapia farming, causing significant economic losses. While vaccination offers protection, commercial vaccines often show inconsistent efficacy due to serotype variation, regional strain shifts, and limited availability in Southeast Asia. The objective of this study was to establish and evaluate a simple, locally adaptable, and back-to-basic vaccination strategy using two bivalent formulations, heat-killed vaccine (HKV) and formalin-killed vaccine (FKV), against Streptococcus agalactiae serotypes Ia and III. Tilapia received a primary intraperitoneal injection followed by a booster dose after 4 weeks. In the lab, vaccinated fish exhibited sustained IgM antibody responses against both serotypes for 84 days, with peak levels on days 35–42 after the booster. Challenge trials with lethal doses demonstrated high relative percent survival (RPS), reaching 97.4–100% for serotype Ia and 86.8–97.4% for serotype III, showing comparable protection between HKV and FKV. Given its simple preparation, scalability, safety, and rapid production without the use of toxic chemicals while retaining bacterial extracellular products, the HKV vaccine was further evaluated on a commercial farm. The HKV elicited a significant serum IgM antibody response in vaccinated tilapia, which remained elevated for up to 126 days and conferred protection during a natural disease outbreak. At the end of our six-month trial, survival rate in the vaccinated treatment was on average 94.5%, significantly higher than the control group at 66.8%. Moreover, the vaccine application significantly lowered feed conversion ratio, increased total biomass, and enhanced revenue by approximately 45%, resulting in higher profit. These findings demonstrate that the basic bivalent HKV is an effective, practical, and locally feasible alternative to commercial vaccines for controlling streptococcosis in tilapia, offering a promising strategy for widespread adoption in resource-limited aquaculture settings.VeterinaryArticleSCOPUS10.3389/fvets.2026.17407572-s2.0-10503247202822971769