Efficient production of recombinant glycoprotein D of herpes simplex virus type 2 in Pichia pastoris and its protective efficacy against viral challenge in mice

Abstract

Herpes simplex virus type 2 (HSV-2) infection is the leading cause of genital ulcer disease and a significant public health concern. However, there are no approved vaccines available to prevent HSV-2 infection. The glycoprotein D (gD) of HSV-2 is the most important candidate antigen for vaccine development. In this study, a truncated form of gD (codons 1-340, gD) was produced as a secretory protein in the methylotrophic yeast Pichia pastoris. The recombinant gD with a His tag was purified to homogeneity by one-step affinity chromatography. Mice immunized with the recombinant gD developed high levels of antigen-specific antibody responses with HSV-2 neutralizing activity. Immunization with the recombinant gD conferred significant protection against lethal HSV-2 infection in mice. Moreover, measurement of the secretion of gD-specific cytokines demonstrated that the recombinant gD induced mixed Th1/Th2 cellular immune responses. These findings indicated that P. pastoris-derived gD represents a promising HSV-2 vaccine candidate with strong immunogenicity and prophylactic efficacy.