Objective  Four combinations of Porcine reproductive and respiratory syndrome (PRRS) vaccine including live vaccine and inactivated vaccine were designed to improve the best immune effect for piglets, which would provide the reference for the formulation of PRRS vaccine prevention and control program.

  Methods  A total of 25 piglets aged 28–35 days were randomly divided into 5 groups. In group A, piglets were firstly immunized with the live vaccine of PRRS (CH-1R strain) from manufacturer A and secondly immunized with the inactivated vaccine of PRRS (CH-1a strain ) from manufacturer A at an interval of 14 days. In group B, they was firstly immunized with the live vaccine of PRRS (strain CH-1R) B and secondly inactivated with the inactivated vaccine of PRRS (CH-1a strain) from manufacturer B, respectively. In group C, they was immunized for two times with the inactivated vaccine of PRRS (CH-1a strain) from manufacturer A. The interval of two immunization was 14 days, and 2 mL vaccine was injected into each piglet muscle. In group D, they was immunized for two times with the inactivated vaccine of PRRS (CH-1a strain) from manufacturer B. Group E was the control. The levels of cytokines (IL-2, IFN-γ, IFN-α, TNF-α) in peripheral blood were detected before and 1, 3, 5, 7 days after immunization. Blood samples were collected before the first immunization, 14 days after the first immunization, and 7, 14, 21 and 28 days after the second immunization to detect the levels of antibodies anti-GP5 protein and N protein. All groups were challenged with PRRSV at the 28^th day after the second immunization, and body temperature was detected for 21 days after PRRSV challenge, and necropsy was performed at the 21^st day after the PRRSV challenge.

  Results  The test results showed that the mRNA expression levels of cytokines in all groups showed different change trend in control group after first immunization, the IL-2 expression levels decreased along with the increase of day age, but it in group A, B were significantly higher than those of group C, D, E at the 3^rd day; the expression level of IFN-γ in groups C and D were significantly higher than those in groups A and B at 3^rd day, 5^th day and 7^th day; the expression level of IFN-α in group B was significantly higher than that in other groups at the 3^rd day, 5^th day and 7^th day, and the expression level of TNF-α in group A was significantly higher than those in other groups at the 7^th day. After PRRSV wide strain challenge, the temperature of the control group rose quickly and high, and the duration of high temperature was long. The temperature of piglets in groups B increased less, and quickly returned to normal temperature. After immunization, the antibody level, antibody positive rate and challenge protection rate were the highest in group B.

  Conclusion  The immune effect of live vaccine and inactivated vaccine of PRRS combination immunization is better than that of inactivated vaccine combination immunization, and the immune effect of vaccine from manufacturer B is better than that from manufacturer A.