title: Norovirus P particle efficiently elicits innate, humoral and cellular immunity.
abstract: Norovirus (NoV) P domain complexes, the 24 mer P particles and the P dimers, induced effective humoral immunity, but their role in the cellular immune responses remained unclear. We reported here a study on cellular immune responses of the two P domain complexes in comparison with the virus-like particle (VLP) of a GII.4 NoV (VA387) in mice. The P domain complexes induced significant central memory CD4(+) T cell phenotypes (CD4(+) CD44(+) CD62L(+) CCR7(+)) and activated polyclonal CD4(+) T cells as shown by production of Interleukin (IL)-2, Interferon (IFN)-γ, and Tumor Necrosis Factor (TNF)-α. Most importantly, VA387-specific CD4(+) T cell epitope induced a production of IFN-γ, indicating an antigen-specific CD4(+) T cell response in P domain complex-immunized mice. Furthermore, P domain complexes efficiently induced bone marrow-derived dendritic cell (BMDC) maturation, evidenced by up-regulation of co-stimulatory and MHC class II molecules, as well as production of IL-12 and IL-1β. Finally, P domain complex-induced mature dendritic cells (DCs) elicited proliferation of specific CD4(+) T cells targeting VA387 P domain. Overall, we conclude that the NoV P domain complexes are efficiently presented by DCs to elicit not only humoral but also cellular immune responses against NoVs. Since the P particle is highly effective for both humoral and cellular immune responses and easily produced in Escherichia coli (E. coli), it is a good choice of vaccine against NoVs and a vaccine platform against other diseases.
authors: Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
authors: Hao
authors: H
authors: Fang
authors: Ming
authors: M
authors: Tan
authors: Ming
authors: M
authors: Xia
authors: Leyi
authors: L
authors: Wang
authors: Xi
authors: X
authors: Jiang
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D005260:Female; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D029322:Norovirus / Q000276:immunology*; D017434:Protein Structure, Tertiary; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D058425:Vaccines, Virus-Like Particle / Q000737:chemistry* / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D058425:Vaccines, Virus-Like Particle; D007371:Interferon-gamma
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