White spot syndrome virus (WSSV) is the pathogen agent of a white spot disease causing significant mortalities in shrimp, crab and other crustaceans. In this study, the protective efficacy of a DNA construct encoding WSSV viral protein 28 (VP28) gene encapsulated with chitosan/Tripolyphosphate (CS/TPP) nanoparticles was examined in marine water crab (Scylla serrate). Oral administration was done using pcDNA 3.1/VP28 plasmid (pVP28) concentration of 100 μg/g when conjugated with 1 mg of TPP was added drop by drop into 50 ml of CS solution. This combination of nanoparticles was provide to be more active to increasing the survivability of the infected crab. CS/TPP were characterized by transmission electron microscope (TEM). Outcome of this study showed the availability of the pVP28 construct up to 10th day post treatment. The oral administration was given to be better treatment. © 2020 Elsevier Ltd