LAUSR

ABSTRACT Rotavirus (RV) inner capsid VP6 protein is a potential non‐live vaccine candidate due to high degree of conservation and immunogenicity, and ability to self‐assemble into oligomeric structures, including nanotubes. These VP6 structures induce strong humoral and T cell immunity and protect mice against RV challenge. It has been suggested that intracellular neutralization by IgA antibody and VP6‐specific CD4+ T cells mediate protection. We investigated generation of diverse CD4+ T cell subsets by intradermal and intranasal delivery of recombinant VP6 (rVP6) nanotubes in BALB/c mice. Production of antiviral cytokine interferon‐&ggr; (IFN‐&ggr;), interleukin‐4 (IL‐4) and pro‐inflammatory cytokine IL‐17 was analyzed following in vitro stimulation of immune cells. Cell surface CD107a expression was measured to determine VP6‐specific cytotoxic T cells. Both parenteral and mucosal immunization with oligomeric rVP6 induced VP6‐specific Th1, Th2 and Th17 cells. For the first time, cytotoxicity‐related degranulation (CD107a surface expression) indicated that RV VP6‐specific CD4+ T cells had cytotoxic T lymphocyte (CTL) phenotype. These findings demonstrate an ability of rVP6 nanostructures to induce heterogeneous CD4+ T cells with different effector functions, including CTLs with potential to lyse RV‐infected cells, suggesting an additional mechanism of RV VP6‐induced protection. HighlightsBoth intradermal and intranasal immunization of mice with oligomeric RV rVP6 induced Th1, Th2, and Th17 cells.Degranulation assay showed that VP6‐specific CD4+ T cells possess cytotoxic T lymphocyte phenotype.These findings demonstrate an ability of rVP6 to induce heterogeneous CD4+ T cells with different effector functions.