This paper described a kind of subunit vaccine, and the effect of Anabaena-expressed VP28 against white spot syndrome virus (WSSV) and the related immune response in Litopenaeus vannamei. Firstly, L. vannamei was orally administered by feeding Anabaena-expressed VP28 for 7 days. Secondly, the shrimp was challenged with WSSV and its mortality was monitored. Finally, the shrimp related immune index was measured. The results revealed that Anabaena-expressed vp28 can significantly improve the shrimp's ability against WSSV. The survival rate of feeding and immersing infected WSSV is 78.80% and 83.19% respectively. The results showed that oral agent can enhance the ability against WSSV in L. vannamei. After shrimp was administrated by Anabaena-expressed vp28, the shrimp enzyme acitivity at different time points showed that superoxide dismutase (SOD), phenoloxidase (PO), catalase (CAT), alkaline phosphatase (AKP) at 2 h after immunization were rising, and reached peak at 48 h or 96 h, which suggested that oral agent could cause the change of enzyme activity. The enzyme activity of shrimp hepatopancreas and muscle after feeding infection showed that the SOD activity of experimental group in hepatopancreas after challenge was 42.10%, 32.26% and 16.04% higher than those of the positive group, wide type group and blank group. In muscle, SOD activity was 17.70%, 11.50%, 15.00% and 10.00% higher than those of negative control, positive control, wide type and blank group after challenge. And the PO activity, CAT activity, and AKP activity of the experimental group were 12.17%, 88.80% and 240.07% higher than that of the positive control after challenge in hepatopancreas respectively. The PO activity, CAT activity, and AKP activity of the experimental group were 21.49%, 30.90% and 100% higher than that of wide type after challenge in hepatopancreas respectively. ACP activity was slightly higher than that of negative control, but ACP activity had no significant difference in the muscle groups. The results of shrimp PO, CAT, AKP and ACP activity of immersing infection were similar to feeding infection. The experiment group CAT and AKP activity after immersing infection is significantly higher than other groups, and the CAT activity of immersing infection were more significant than feeding infection. The PO activity of shrimp hepatopancreas of experiment group after immersing infection was significantly higher than those of positive control, wide type and blank, but ACP activity of different group was not significantly different. This paper showed that Anabaena-expressed vp28 can strengthen shrimp's resistance to WSSV and decrease the mortality of L. vannamei from white spot disease. The Anabaena-expressed vp28 can be drug and feed from the same feedstock without purification, which has great application potential for field use in large-scale production.