Response of dendritic cells and T cells to virus-like particles formed from norovirus viral protein-1 (VP1N) or chimeric molecules containing a fragment of VP1N and polypeptides of echovirus 30
摘要
Virus-like particles (VLPs) are considered as promising components of vaccines. We studied the response of human dendritic cells (DCs) and naïve CD4+ T cells in vitro and the response of murine T cells in vivo to VLPs derived from VP1N, from a fragment of this protein containing the shell domain and hinge region (SN), or from chimeric molecules obtained by genetic fusion of SN with the VP1, VP2, or VP3 polypeptides of echovirus 30 (SN-VP1E30, SN-VP2E30, and SN-VP3E30). Norovirus VLPs were efficiently endocytosed and stimulated the maturation of monocyte-derived DCs and conventional blood-borne CD1c+CD141− DCs. Chimeric SN-VP2E30 VLPs strongly stimulated DC maturation, SN-VP3E30 VLPs had a weak effect, but a mixture of these VLPs potently induced DC maturation. VLP-treated DCs enhanced cytokine production and increased the ability to induce differentiation of human naïve CD4+ T cells into T helper type 1 cells. Immunization of mice with VP1N VLPs, SN-VP2E30 VLPs or a mixture of SN-VP1E30, SN-VP2E30 and SN-VP3E30 VLPs increases the number of CD4+ splenocytes capable of proliferating in response to the antigens of all particles administered to the mouse, as well as CD8+ splenocytes capable of proliferating in response to VP2E30 or SN-VP1E30. Immunization of mice with VLPs resulted in increased IFN-γ production by splenocytes stimulated ex vivo with VP1N, VP2E30, and SN-VP3E30. In addition, immunization with SN-VP2E30 VLPs resulted in increased IL-5 production by splenocytes in response to specific antigens. The results indicate the ability of norovirus VLPs and chimeric VLPs to induce T cell responses.