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.
Highlights
Viruses are increasingly being used in nanotechnology applications for a variety of purposes as diverse as material science, vaccine development, and therapeutic design
We found that Cowpea mosaic virus (CPMV) is bound and internalized by subsets of several populations of antigen presenting cells (APCs) both in vitro and in vivo following intravenous, intraperitoneal, and oral administration, and by cells isolated from the Peyer’s patch following gastrointestinal delivery
Surface vimentin was expressed on APC populations that could internalize CPMV
Summary
Viruses are increasingly being used in nanotechnology applications for a variety of purposes as diverse as material science, vaccine development, and therapeutic design. A variety of plant pathogens such as cowpea mosaic virus (CPMV) [2,3,4,5,6,7], cucumber mosaic virus (CMV) [8,9], alfalfa mosaic virus (AlMV) [10], tobacco mosaic virus (TMV) [11,12,13] and papaya mosaic virus (PapMV) [14] have been exploited for vaccine purposes, whereby the viruses are modified to present antigens through genetic introduction of foreign epitopes and proteins, combining engineering of the multivalent antigen with large-scale production of the antigen in plants. A variety of bioconjugation methods have been developed, with surface lysines or introduced cysteines most typically utilized Plant 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. 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
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