title: Plant viral nanoparticles-based HER2 vaccine: Immune response influenced by differential transport, localization and cellular interactions of particulate carriers.
abstract: Cancer vaccines are designed to elicit an endogenous adaptive immune response that can successfully recognize and eliminate residual or recurring tumors. Such approaches can potentially overcome shortcomings of passive immunotherapies by generating long-lived therapeutic effects and immune memory while limiting systemic toxicities. A critical determinant of vaccine efficacy is efficient transport and delivery of tumor-associated antigens to professional antigen presenting cells (APCs). Plant viral nanoparticles (VNPs) with natural tropism for APCs and a high payload carrying capacity may be particularly effective vaccine carriers. The applicability of VNP platform technologies is governed by stringent structure-function relationships. We compare two distinct VNP platforms: icosahedral cowpea mosaic virus (CPMV) and filamentous potato virus X (PVX). Specifically, we evaluate in vivo capabilities of engineered VNPs delivering human epidermal growth factor receptor 2 (HER2) epitopes for therapy and prophylaxis of HER2+malignancies. Our results corroborate the structure-function relationship where icosahedral CPMV particles showed significantly enhanced lymph node transport and retention, and greater uptake by/activation of APCs compared to filamentous PVX particles. These enhanced immune cell interactions and transport properties resulted in elevated HER2-specific antibody titers raised by CPMV- vs. PVX-based peptide vaccine. The 'synthetic virology' field is rapidly expanding with numerous platforms undergoing development and preclinical testing; our studies highlight the need for systematic studies to define rules guiding the design and rational choice of platform, in the context of peptide-vaccine display technologies.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Electronic address: sourabh.shukla@case.edu.
authors.forename: Sourabh
authors.initials: S
authors.lastname: Shukla
authors.affiliation: Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Jay T
authors.initials: JT
authors.lastname: Myers
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Woods
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Xingjian
authors.initials: X
authors.lastname: Gong
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Czapar
authors.affiliation: Department of Molecular Biotechnology, RWTH-Aachen University, 52064 Aachen, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Commandeur
authors.affiliation: Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USA; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Alex Y
authors.initials: AY
authors.lastname: Huang
authors.affiliation: Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Levine
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA; Department of Radiology, Case Western Reserve University, Cleveland, OH 44106, USA; Department of Materials Science and Engineering, Case Western Reserve University, Cleveland, OH 44106, USA; Department of Macromolecular Science and Engineering, Case Western Reserve University, Cleveland, OH 44106, USA; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA; Division of General Medical Sciences-Oncology, Case Western Reserve University, Cleveland, OH 44106, USA. Electronic address: nicole.steinmetz@case.edu.
authors.forename: Nicole F
authors.initials: NF
authors.lastname: Steinmetz
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D001693:Biological Transport, Active / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D009374:Neoplasms, Experimental / Q000276:immunology*; D009858:Oncogenic Viruses / Q000276:immunology*; D010942:Plant Viruses / Q000276:immunology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D013347:Subcellular Fractions / Q000276:immunology*; D014771:Virion / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Antigen delivery; Cancer vaccine; HER2; Peptide vaccine; Viral nanoparticles