Zymosan enhances the immune response to DNA vaccine for human immunodeficiency virus type‐1 through the activation of complement system

Abstract

In the present study, the adjuvant effect of zymosan on human immunodeficiency virus type-1 (HIV-1)-specific DNA vaccine and the mechanism of this enhancement were studied in a murine model. We coinoculated zymosan with our candidate HIV-1 specific DNA vaccine (pCMV160IIIB) into skeletal muscles of BALB/c mice. Higher levels of both humoral immune response and HIV-specific delayed-type hypersensitivity (DTH) response were observed when zymosan was coinoculated with pCMV160IIIB compared with that obtained using pCMV160IIIB alone. HIV-specific cytotoxic T lymphocyte (CTL) activity was also enhanced. This enhancing activity was suppressed when coinoculated to the fifth complement (C5)-deficient DDD and AKR mice. The enhanced activity was also suppressed when anti-C3 antibody was inoculated to mice intramuscularly. There was significant induction of immunoglobulin G2a (IgG2a) and interferon-gamma (IFN-gamma) in pCMV160IIIB vaccine with zymosan. These results suggest that zymosan-mediated DNA vaccination enhances helper T cell (Th) 1-mediated immunity. The effect is suggested to be based on the consequences of its recruitment and activation of macrophages, dendritic cells or antigen-presenting cells (APC) through complement activation, especially through the alternative pathway. Taken together, these results suggest that zymosan can be an effective immunological adjuvant in DNA vaccination against HIV-1.