The distinct effects of three tandem repeats of C3d in the immune responses against tumor-associated antigen hCGbeta by DNA immunization.
Several examples have shown that C3d3, when fused to a corresponding antigen, had a strong adjuvant effect on certain specific antibody production. In a previous study, we attempted to prove that this was the case of the human chorionic gonadotrophin beta chain (hCGbeta)-induced immunity following DNA vaccination. However, we found that C3d3 when fused to hCGbeta inhibited rather than enhanced the antigen-specific immune response. In the present study, using hCGbeta DNA vaccine preparations, we demonstrated that C3d3 inhibited the antigen-specific humoral antibody response and several other immune responses, such as the hCGbeta specific lymphoproliferation. Such inhibitory effects of C3d3 were not related to the expression level of the target protein, the gender of the test mice, or the vector used. Contrastingly, C3d3 fused with the envelope protein of hepatitis B virus (PreS2/S) used as a control system resulted in the enhancement of both humoral and cell-mediated antigen-specific immune responses against HBV-preS2/S, which was consistent with other groups' adjuvant-effect findings. We further showed that the mechanisms involved in the inhibitory effect of C3d3 might be possible due to impairing the function of antigen presenting B lymphocytes and reducing the expression of transcription factors (T-bet and GATA-3) and cytokine IL-4. Collectively, unlike its usual expected adjuvant function, the fusion of C3d3 with the tumor-associated antigen hCGbeta was found to inhibit both humoral and cell-mediated antigen-specific immune responses. These findings indicate that research concerning tumor immune escapes and vaccine designs require further extensive attention.
Guan
Qing Dong
QD
Institute for Immunobiology and Department of Immunology, Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
Wang
Ying
Y
Chu
Yi Wei
YW
Wang
Li Xin
LX
Ni
Jing
J
Guo
Qiang
Q
Xiong
Si Dong
SD
D000276:Adjuvants, Immunologic; D000818:Animals; D000915:Antibody Affinity; D000917:Antibody Formation; D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000276:immunology*; D015933:Complement C3d / Q000235:genetics / Q000276:immunology*; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011498:Protein Precursors / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020080:Tandem Repeat Sequences; D019444:Vaccines, DNA / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D018997:Chorionic Gonadotropin, beta Subunit, Human; D006514:Hepatitis B Surface Antigens; D011498:Protein Precursors; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; C050807:presurface protein 2, hepatitis B surface antigen; D015933:Complement C3d