TY - JOUR
T1 - Whole recombinant Hansenula polymorpha expressing hepatitis B virus surface antigen (yeast-HBsAg) induces potent HBsAg-specific Th1 and Th2 immune responses
AU - Bian, Guanglin
AU - Cheng, Yuming
AU - Wang, Zekun
AU - Hu, Yunwen
AU - Zhang, Xiaonan
AU - Wu, Min
AU - Chen, Zhiao
AU - Shi, Bisheng
AU - Sun, Shuhui
AU - Shen, Yan
AU - Chen, Er jia
AU - Yao, Xin
AU - Wen, Yumei
AU - Yuan, Zhenghong
N1 - Funding Information:
We thank Dr Wenjiang Zhou, Hua Yang (the animal house of Shanghai Public Health Clinical Center) for the excellent assistance in mice breeding. We also thank Xin Yao, Jing wang, Wei Wang, Shengfu Dong (Fudan University) for the expert technical assistance. This work was supported by the Chinese State Basic Research Foundation Grant (Grant No. 2005CB522902 ), National High Tech. Research Developing Program (20060102A4018) and National Mega Project for Infectious Diseases (2008ZX10002-002), Shanghai Program for Outstanding Medical Academic Leader. Guanglin Bian was supported by a Ph.D. studentship from Fudan University.
Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2009/12/10
Y1 - 2009/12/10
N2 - Recent studies have suggested that yeast cell wall components possess adjuvant activities. In the present study, heat-killed whole recombinant Hansenula polymorpha yeast expressing hepatitis B surface antigen (yeast-HBsAg) was generated, and the immune responses elicited by yeast-HBsAg were investigated in mice. The studies showed that yeast-HBsAg as well as yeast greatly promotes the accumulation of immune cells in mouse spleen and contributes to the maturation of dendritic cells (DCs). Yeast-HBsAg not only induces significantly higher antibody responses (including IgG, IgG1 and IgG2a), but also increases the IgG2a/IgG1 ratio, while alum combined with HBsAg (HBsAg + alum) only enhances antibody responses, but not the IgG2a/IgG1 ratio compared to HBsAg alone. Analysis of HBsAg-specific cytokines revealed that yeast-HBsAg is associated with production of both IFN-γ and IL-4, but neither IFN-γ nor IL-4 was detected in the HBsAg + alum-immunized group. Moreover, yeast-HBsAg induces potent HBsAg-specific lymphocyte proliferation and Cytotoxic T lymphocyte (CTL) responses. In conclusion, yeast-HBsAg enhances both HBsAg-specific Th1 and Th2 immune responses, while alum only enhances Th2 immune responses, suggesting that yeast-HBsAg may be an ideal candidate for an effective vaccine for the control of chronic hepatitis B virus (HBV) infection.
AB - Recent studies have suggested that yeast cell wall components possess adjuvant activities. In the present study, heat-killed whole recombinant Hansenula polymorpha yeast expressing hepatitis B surface antigen (yeast-HBsAg) was generated, and the immune responses elicited by yeast-HBsAg were investigated in mice. The studies showed that yeast-HBsAg as well as yeast greatly promotes the accumulation of immune cells in mouse spleen and contributes to the maturation of dendritic cells (DCs). Yeast-HBsAg not only induces significantly higher antibody responses (including IgG, IgG1 and IgG2a), but also increases the IgG2a/IgG1 ratio, while alum combined with HBsAg (HBsAg + alum) only enhances antibody responses, but not the IgG2a/IgG1 ratio compared to HBsAg alone. Analysis of HBsAg-specific cytokines revealed that yeast-HBsAg is associated with production of both IFN-γ and IL-4, but neither IFN-γ nor IL-4 was detected in the HBsAg + alum-immunized group. Moreover, yeast-HBsAg induces potent HBsAg-specific lymphocyte proliferation and Cytotoxic T lymphocyte (CTL) responses. In conclusion, yeast-HBsAg enhances both HBsAg-specific Th1 and Th2 immune responses, while alum only enhances Th2 immune responses, suggesting that yeast-HBsAg may be an ideal candidate for an effective vaccine for the control of chronic hepatitis B virus (HBV) infection.
KW - H. polymorpha
KW - HBV vaccine
KW - Th1 immune responses
UR - http://www.scopus.com/inward/record.url?scp=70649115445&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2009.09.101
DO - 10.1016/j.vaccine.2009.09.101
M3 - Article
C2 - 19789093
AN - SCOPUS:70649115445
SN - 0264-410X
VL - 28
SP - 187
EP - 194
JO - Vaccine
JF - Vaccine
IS - 1
ER -
