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

Date Published: November 23, 2009

Publisher: Public Library of Science

Author(s): Maria J. Gonzalez, Emily M. Plummer, Chris S. Rae, Marianne Manchester, Mauricio Martins Rodrigues.

Abstract: 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. 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.

Partial Text: Viruses are increasingly being used in nanotechnology applications for a variety of purposes as diverse as material science, vaccine development, and therapeutic design. For many years animal viruses have been developed for gene delivery and gene therapy purposes [1]. More recently, other pathogens such as plant viruses, bacteriophages and viruses of Archaea are increasingly being used for nanobiotechnology purposes because of their relative structural and chemical stability, ease of production, and lack of toxicity and pathogenicity in animals or humans [2], [3], [4], [5]. In particular, plant viruses have been at the forefront of efforts to develop novel vaccines, in part because of the potential for producing large quantities of antigenic material in plant hosts, as well as the possibility for developing orally-bioavailable antigens. 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, thus combining engineering of the multivalent antigen with large-scale production of the antigen in plants.

This study shows that in vitro, CPMV binds to and is internalized by APCs such as BalbCl7, MC57 and imDCs derived from mouse bone marrow. Moreover, DCs, macrophages, B cells and NK cells have the ability to capture CPMV particles in vivo following intravenous, intraperitoneal, and oral administration. Interaction of CPMV and APCs correlates with surface expression of the CPMV binding protein, surface vimentin. Following oral administration, CPMV associated with the gastrointestinal epithelium, in particular PP. CPMV could also be detected in APCs isolated from PP. Together these results indicate that CPMV can interact with APCs by a variety of routes of administration.



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