Immune Protection Gap Between Porcine Reproductive and Respiratory Syndrome Subunit Vaccine (N Protein) and Live Vaccine

<b>Objectives</b>: To evaluate the immunoprotective effect of a PRRSV N protein subunit vaccine on piglets using a live PRRSV vaccine as a control. <b>Methods</b>: The HEK-293T eukaryotic expression system was used to produce PRRSV N protein, and then PRRSV N protein was immunized with a commercial live PRRS vaccine. The immunoprotective effect of the PRRSV N protein subunit vaccine on piglets was evaluated by detecting the antibody level in the immunized piglets, and the clinical symptoms, pathological changes, and survival rate of the immunized piglets. <b>Results</b>: At 21 and 28 days after immunization, the serum N protein-specific antibody levels of piglets in the live PRRSV vaccine group were higher than those in the N protein group. After PRRSV infection, piglets in the N protein group and the DMEM group showed more severe clinical symptoms such as respiratory distress, loss of appetite, skin redness, and diarrhea than those in the live vaccine group. The rectal temperature of piglets in the live vaccine group remained below 40 °C, and only one piglet died on day 11 post-infection; in the PRRSV N protein group, the rectal temperature of some piglets exceeded 41 °C, and four piglets died on days 9, 11, 14, and 20 post-infection. In addition, pathologic damage to organs such as lungs, liver, lymph nodes, spleen, and kidneys was more severe in the N protein group than in the live vaccine group. Furthermore, histopathology and immunohistochemistry showed more pronounced organ damage (lungs, liver, lymph nodes, spleen, and kidneys) and higher viral loads in the N protein group compared to the live vaccine group. <b>Conclusions</b>: The PRRS subunit vaccine (N protein) expressed in the HEK-293T eukaryotic system did not protect piglets from heterologous PRRSV infection compared with the PRRS live vaccine.