A Schistosoma japonicum chimeric protein with a novel adjuvant induced a polarized Th1 immune response and protection against liver egg burdens.
BACKGROUND
Schitosomiasis japonica is still a significant public health problem in China. A protective vaccine for human or animal use represents an important strategy for long-term control of this disease. Due to the complex life cycle of schistosomes, different vaccine design approaches may be necessary, including polyvalent subunit vaccines. In this study, we constructed four chimeric proteins (designated SjGP-1~4) via fusion of Sj26GST and four individual paramyosin fragments. We tested these four proteins as vaccine candidates, and investigated the effect of deviating immune response on protection roles in mice.


METHODS
The immunogencity and protection efficacy of chimeric proteins were evaluated in mice. Next, the chimeric protein SjGP-3 was selected and formulated in various adjuvants, including CFA, ISA 206, IMS 1312 and ISA 70M. The titers of antigen-specific IgG, IgE and IgG subclass were measured. The effect of adjuvant on cytokine production and percentages of CD3+CD8-IFN-gamma+ cells and CD3+CD8-IL-4+ cells were analyzed at different time points. Worm burdens and liver egg counts in different adjuvant groups were counted to evaluate the protection efficacy against cercarial challenge.


RESULTS
Immunization of mice with chimeric proteins provided various levels of protection. Among the four proteins, SjGP-3 induced the highest level of protection, and showed enhanced protective efficacy compared with its individual component Sj26GST. Because of this, SjGP-3 was further formulated in various adjuvants to investigate the effect of adjuvant on immune deviation. The results revealed that SjGP-3 formulated in veterinary adjuvant ISA 70M induced a lasting polarized Th1 immune response, whereas the other adjuvants, including CFA, ISA 206 and IMS 1312, generated a moderate mixed Th1/Th2 response after immunization but all except for IMS 1312 shifted to Th2 response after onset of eggs. More importantly, the SjGP-3/70M formulation induced a significant reduction in liver egg deposition at 47.0-50.3% and the number of liver eggs per female at 34.5-37.2% but less effect on worm burdens at only 17.3-23.1%, whereas no effect of the formulations with other adjuvants on the number of liver eggs per female was observed.


CONCLUSIONS
Construction of polyvalent subunit vaccine was capable to enhance immunogenicity and protection efficacy against schistosomiasis. There was correlation of the polarized Th1 response with reduction of liver egg burdens, supporting the immune deviation strategy for schistosomiasis japonica vaccine development.
Xu
Xindong
X
Institute for Infectious Diseases & Vaccine Development, Tongji University School of Medicine, 1239 Siping Road, Shanghai 200092, PR China. xuxd1981@yahoo.com.cn
Zhang
Dongmei
D
Sun
Wei
W
Zhang
Qingfeng
Q
Zhang
Jingjing
J
Xue
Xiangyang
X
Shen
Luhui
L
Pan
Weiqing
W
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood / Q000276:immunology; D000947:Antigens, Helminth / Q000276:immunology* / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D005260:Female; D015801:Helminth Proteins / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008099:Liver / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D010843:Pichia / Q000378:metabolism; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D012549:Schistosoma japonicum / Q000276:immunology / Q000378:metabolism; D012554:Schistosomiasis japonica / Q000276:immunology / Q000517:prevention & control*; D012908:Snails; D018417:Th1 Cells / Q000276:immunology*; D014335:Tropomyosin / Q000276:immunology / Q000378:metabolism; D022223:Vaccines, Subunit / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D015801:Helminth Proteins; D011993:Recombinant Fusion Proteins; D014335:Tropomyosin; D022223:Vaccines, Subunit; D015847:Interleukin-4; D007371:Interferon-gamma