Interaction of Cowpea Mosaic Virus (CPMV) Nanoparticles with Antigen Presenting Cells In Vitro and In Vivo

Abstract

BackgroundPlant viruses such as Cowpea mosaic virus (CPMV) are increasingly being developed for applications in nanobiotechnology including vaccine development because of their potential for producing large quantities of antigenic material in plant hosts. In order to improve efficacy of viral nanoparticles in these types of roles, an investigation of the individual cell types that interact with the particles is critical. In particular, it is important to understand the interactions of a potential vaccine with antigen presenting cells (APCs) of the immune system. CPMV was previously shown to interact with vimentin displayed on cell surfaces to mediate cell entry, but the expression of surface vimentin on APCs has not been characterized.MethodologyThe binding and internalization of CPMV by several populations of APCs was investigated both in vitro and in vivo by flow cytometry and fluorescence confocal microscopy. The association of the particles with mouse gastrointestinal epithelium and Peyer's patches was also examined by confocal microscopy. The expression of surface vimentin on APCs was also measured.ConclusionsWe found that CPMV is bound and internalized by subsets of several populations of APCs both in vitro and in vivo following intravenous, intraperitoneal, and oral administration, and also by cells isolated from the Peyer's patch following gastrointestinal delivery. Surface vimentin was also expressed on APC populations that could internalize CPMV. These experiments demonstrate that APCs capture CPMV particles in vivo, and that further tuning the interaction with surface vimentin may facilitate increased uptake by APCs and priming of antibody responses. These studies also indicate that CPMV particles likely access the systemic circulation following oral delivery via the Peyer's patch.

In situ vaccination with cowpea mosaic virus nanoparticles suppresses metastatic cancer

“…eCPMV has been shown to bind surface vimentin on cancer cells 29,30 and some antigen-presenting cells 31 , although it is not known if murine neutrophils have surface vimentin. eCPMV appears to target quiescent neutrophils and activate them and increases the frequency of CD11b + class-II + CD86 hi tumour-infiltrating neutrophils.…”

Nanoparticle Design Strategies for Effective Cancer Immunotherapy

“…Most of the mice showed continued resistance to B16F10 tumor cells (Figure 2F), suggesting that the systemic immunity is established. eCPMVs have been shown to bind to APCs [70], as well as to vimentin on cancer cells [71, 72] to activate neutrophils, which then recruit CTLs. This monotherapy can be incorporated as one of the treatments to treat the types of cancer mentioned above.…”

Hydrazone Ligation Strategy to Assemble Multifunctional Viral Nanoparticles for Cell Imaging and Tumor Targeting

“…Unmodified CPMV particles are rapidly internalized by a wide variety of cell types in vitro and in vivo 25-27 . This uptake is governed primarily by binding to a cell-surface form of the intermediate filament vimentin 25, 28 , and can be inhibited by PEGylation, 3, 10, 29 a modification that also increases plasma circulation time and should enhance the accumulation of the nanoparticles in target tissues.…”