A novel subunit vaccine based on glycoprotein H and glycoprotein L fusion against pseudorabies virus infection

Pseudorabies (PR) is a highly infectious disease caused by pseudorabies virus (PRV), which leads to significant economic losses. Vaccination remains the most effective method to control PRV infection. To develop an efficient DIVA (differentiation of infected from vaccinated animals) vaccine against PRV, this study expressed the envelope glycoprotein H (gH), glycoprotein L (gL), and a recombinant gH-gL fusion protein in a mammalian cell expression system and evaluated their protective efficacy in a mouse model. Immunization with gH, gL, or gH-gL induced high levels of specific antibodies capable of neutralizing PRV, and elicited a Th1/Th2-mediated immune response. Neutralizing antibody titers in the gH-gL group were significantly higher than those in the other groups. After a lethal challenge with 2 × 10⁴TCID₅₀ of the PRV variant XiangA strain, the survival rate of the gH-gL group was 100%, which was significantly higher than that of the gH (40%) and gL (50%) groups. Even under a higher challenge dose of 10^5.5TCID₅₀, the survival rate in the gH-gL group remained 100%, outperforming that of mice vaccinated with a commercial inactivated vaccine (50%). Furthermore, after challenge, viral loads in tissues of the gH-gL group were almost undetectable, and no obvious pathological changes were observed. Our results demonstrate that the gH-gL recombinant fusion protein is a promising vaccine candidate for preventing and controlling pseudorabies epidemics in China.