Y. Ara et al., Zymosan enhances the immune response to DNA vaccine for human immunodeficiency virus type-1 through the activation of complement system, IMMUNOLOGY, 103(1), 2001, pp. 98-105
In the present study, the adjuvant effect of zymosan on human immunodeficie
ncy virus type-1 (HIV-1)-specific DNA vaccine and the mechanism of this enh
ancement were studied in a murine model. We coinoculated zymosan with our c
andidate 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 we-re observed when zymosan w
as coinoculated with pCMV160IIIB compared with that obtained using pCMV160I
IIB alone. HIV-specific cytotoxic T lymphocyte (CTL) activity was also enha
nced. 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. T
here was significant induction of immunoglobulin G2a (IgG2a) and interferon
-gamma (IFN-gamma) in pCMV160IIIB vaccine with zymosan. These results sugge
st that zymosan-mediated DNA vaccination enhances helper T cell (Th) 1-medi
ated immunity. The effect is suggested to be based on the consequences of i
ts recruitment and activation of macrophages, dendritic cells or antigen-pr
esenting 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.