Virus-Like Particles Formed From Viral Protein 1 (VP1) of Norovirus GII.4 Sydney 2012 Enhance the Ability of Human Dendritic Cells to Stimulate CD4⁺ T Cells in Vitro

Noroviruses are the leading cause of outbreaks of nonbacterial gastroenteritis and the second most common cause of all viral intestinal infections. An effective norovirus vaccine is expected to help reduce the incidence of intestinal infections, but intensive efforts to develop such a vaccine have so far been unsuccessful. Failures in vaccine development may be due to the high heterogeneity of noroviruses and/or the hypothetical low protective efficacy of the immune response to the most common virus variants, such as GII.4 Sydney 2012. The subject of the study was potential vaccine components – virus-like particles (VLPs), formed from VP1 of norovirus GII.4 Sydney 2012 (VP1N) and VLPs from a fragment of this protein containing the shell domain and hinge region (SN). We investigated the effect of VLPs on the ability of human dendritic cells (DCs) to recruit T cells into the immune response in vitro. VLP-treated DCs were cultured with pure CD4⁺ T cells, and then T cell maturity and cytokine production were assessed. It has been shown that VP1N-treated DCs, but not SN-treated DCs, have an increased ability to shift the ratio of T cell from naïve T cells to more mature central memory T cells and stimulate IL-17 production. Intracellular cytokine assay revealed no differences in T-helper type 1 (Th1), Th17 and Th1/17 levels between mixed cultures with VP1N-treated DCs and control DCs. Apparently, the increase in IL-17 production occurs due to an increase in the activity of mature Th17, and not the maturation of new producer cells.