title: Difference of T cell and B cell activation in two homologous proteins with similar antigenicity but great distinct immunogenicity.
abstract: The candidate particulate hepatitis E vaccine, HEV 239, has been shown to be an efficacious vaccine in primates, and clinical study to date shows it to be safe and immunogenic for humans. The antigenicity of HEV 239 is virtually identical to its N-terminal 26 amino acids truncated protein, E2, which is not particulate but soluble. However, HEV 239 is over 200 times more immunogenic than E2. In present study, several events underlying this dramatic immunogenicity difference have been addressed. (1) HEV 239 can efficiently evoke a vigorous and predominant T cell response while E2 cannot induce detectable T cell response; (2) the dominant T cell epitopes in HEV 239 are identified, and both are also contained integrally in E2; (3) priming mice with Th epitope peptide can partially rescue the weak immunogenicity of E2 in alum adjuvant and (4) HEV 239 but not E2 can induce significant antibody response in athymic mice, which indicates that HEV 239 can directly activate B cell more efficiently. These results contribute to a better understanding of the mechanisms involved in the significant high immunogenicity of particulate antigen and may provide knowledge for the rational design and development of future vaccines.
authors.affiliation: National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen 361005, China. wuting@xmu.edu.cn <wuting@xmu.edu.cn>
authors.forename: Ting
authors.initials: T
authors.lastname: Wu
authors.forename: Xiao-lu
authors.initials: XL
authors.lastname: Wu
authors.forename: Shan-hai
authors.initials: SH
authors.lastname: Ou
authors.forename: Chun-xin
authors.initials: CX
authors.lastname: Lin
authors.forename: Tong
authors.initials: T
authors.lastname: Cheng
authors.forename: Shao-wei
authors.initials: SW
authors.lastname: Li
authors.forename: Mun Hon
authors.initials: MH
authors.lastname: Ng
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Ning-shao
authors.initials: NS
authors.lastname: Xia
mesh_terms: D000956:Antigens, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D016752:Hepatitis E virus / Q000276:immunology*; D007125:Immunogenetics; D008213:Lymphocyte Activation / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*; D014761:Viral Hepatitis Vaccines
chemical_list: D000956:Antigens, Viral; D014759:Viral Envelope Proteins; D014761:Viral Hepatitis Vaccines