The intranasal delivery of non-specific virus-like particles elicits heightened and accelerated immune responses to influenza virus (49.27)

Abstract

Abstract We have previously shown that the intranasal delivery of a small heat-shock protein cage nanoparticle, a virus-like particle (VLP), elicits the formation of inducible bronchus-associated lymphoid tissue (iBALT), which provides protection against many diverse high-dose pathogen challenges. We demonstrate here that the presence of non-specific, VLP-induced iBALT facilitated accelerated influenza virus clearance and enhanced immunity through accelerated airway (CD103+) and parenchymal (CD11b+) dendritic cell antigen processing and trafficking. These responses were dependent upon the presence of CD11c+ cells, which had been directly exposed to VLPs, and migrated into the lung in a CCR2, VCAM-1, and ICAM-1-dependent manner. The initial innate response to influenza challenge was then followed by an accelerated expansion of influenza-specific CD4+ T cells. The combination of these events resulted in accelerated viral clearance and significantly ameliorated host-derived collateral damage. Furthermore, we show that the presence of iBALT, which is not specific to influenza virus, was efficient at clearing high-dose virus, independently of the TBLN’s help. Thus, we herein demonstrate the mechanism by which the presence of iBALT, derived from non-specific, non-pathogenic VLPs, and lacking any memory cells to agents of subsequent challenge, elicited alternative cellular trafficking and expansion patterns, and thus cleared virus at an accelerated rate, with less harmful consequence.