Zymosan enhances the immune response to DNA vaccine for human immunodeficiency virus type-1 through the activation of complement system.
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.
Ara
Y
Y
Departments of Orthopaedic Surgery, Internal Medicine, Pathology, Critical Care and Emergency Medicine, and Bacteriology, Yokohama City University School of Medicine, Yokohama, Japan.
Saito
T
T
Takagi
T
T
Hagiwara
E
E
Miyagi
Y
Y
Sugiyama
M
M
Kawamoto
S
S
Ishii
N
N
Yoshida
T
T
Hanashi
D
D
Koshino
T
T
Okada
H
H
Okuda
K
K
D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic; D000818:Animals; D003167:Complement Activation / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D015483:HIV Antibodies / Q000096:biosynthesis; D015497:HIV-1 / Q000276:immunology*; D007111:Immunity, Cellular; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*; D015054:Zymosan / Q000276:immunology*
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D016207:Cytokines; D015483:HIV Antibodies; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D015054:Zymosan