An oral pH-responsive Streptococcus agalactiae vaccine formulation provides protective immunity to pathogen challenge in tilapia: A proof-of-concept study

Abstract

Intensive tilapia farming has contributed significantly to food security as well as to the emergence of novel pathogens. This includes Streptococcus agalactiae or Group B Streptococcus (GBS) sequence type (ST) 283, which caused the first known outbreak of foodborne GBS illness in humans. An oral, easy-to-administer fish vaccine is needed to reduce losses in fish production and the risk of zoonotic transmission associated with GBS. We conducted a proof-of-concept study to develop an oral vaccine formulation that would only release its vaccine cargo at the site of action, i.e., in the fish gastrointestinal tract, and to evaluate whether it provided protection from experimental challenge with GBS. Formalin-inactivated S. agalactiae ST283, was entrapped within microparticles of Eudragit® E100 polymer using a double-emulsification solvent evaporation method. Exposure to an acidic medium simulating the environment in tilapia stomach showed that the size of the vaccine-loaded microparticles decreased rapidly, reflecting microparticle erosion and release of the vaccine cargo. In vivo studies in tilapia showed that oral administration of vaccine-loaded microparticles to fish provided significant protection from subsequent homologous pathogen challenge with GBS ST283 by immersion compared to the control groups which received blank microparticles or buffer, reducing mortality from 70% to 20%. The high efficacy shows the promise of the vaccine platform developed herein, which might be adapted for other bacterial pathogens and other fish species.