Internalization and antigen presentation by mouse dendritic cells of rotavirus VP6 preparations differing in nanostructure

Abstract

Nanoparticles are highly immunogenic due to the multivalent, repetitive antigen expression and direct activation of antigen presenting cells (APCs), key players of adaptive immune responses. Different virus-like particles (VLPs) have been used as display platforms to amplify immune responses to biologically relevant, but poorly immunogenic foreign antigens. A candidate platform based on rotavirus (RV) inner-capsid protein VP6 oligomers, such as nanotubes (T-VP6) and nanospheres (S-VP6), is also considered. Different VP6 nanostructures were compared for internalization and antigen presentation by the APCs. We found, that a lack of a high-order structures, T-VP6 and S-VP6, did not negatively affect VP6 uptake and presentation by murine bone-marrow derived dendritic cells (BMDCs) in vitro. Furthermore, T-VP6 was preferable to norovirus (NoV) VLPs for BMDC internalization resulting in significantly higher VP6-specific immune responses when T-VP6 and NoV VLP pulsed BMDCs were transferred to syngeneic mice. These results support the use of different VP6 nanostructures as foreign antigen delivery platforms.