The impact of size on particle drainage dynamics and antibody response

Simon Zinkhan; Anete Ogrina; Ina Balke; Gunta Reseviča; Andris Zeltins; Simone de Brot; Cyrill Lipp; Xinyue Chang; Lisha Zha; Monique Vogel; Martin F Bachmann; Mona O Mohsen

doi:10.1016/j.jconrel.2021.01.012

The impact of size on particle drainage dynamics and antibody response

J Control Release. 2021 Mar 10:331:296-308. doi: 10.1016/j.jconrel.2021.01.012. Epub 2021 Jan 12.

Authors

Affiliations

¹ Department of BioMedical Research, University of Bern, Bern, Switzerland; Department of Immunology RIA, University Hospital Bern, Bern, Switzerland.
² Latvian Biomedical Research & Study Centre, Ratsupites iela 1, Riga, LV 1067, Latvia.
³ COMPATH, Institute of Animal Pathology, University of Bern, Bern, Switzerland.
⁴ International Immunology Center, Anhui Agricultural University, Hefei, Anhui, China.
⁵ Department of BioMedical Research, University of Bern, Bern, Switzerland; Department of Immunology RIA, University Hospital Bern, Bern, Switzerland; Jenner Institute, Nuffield Department of Medicine, University of Oxford, UK.
⁶ Department of BioMedical Research, University of Bern, Bern, Switzerland; Department of Immunology RIA, University Hospital Bern, Bern, Switzerland; Interim Translational Research Institute "iTRI", National Center for Cancer Care & Research Doha, Qatar. Electronic address: mona.mohsen@dbmr.unibe.ch.

PMID: 33450322
DOI: 10.1016/j.jconrel.2021.01.012

Abstract

Vaccine-induced immune response can be greatly enhanced by mimicking pathogen properties. The size and the repetitive geometric shape of virus-like particles (VLPs) influence their immunogenicity by facilitating drainage to secondary lymphoid organs and enhancing interaction with and activation of B cells and innate humoral immune components. VLPs derived from the plant Bromovirus genus, specifically cowpea chlorotic mottle virus (CCMV), are T = 3 icosahedral particles. (T) is the triangulation number that refers to the number and arrangements of the subunits (pentamers and hexamers) of the VLPs. CCMV-VLPs can be easily expressed in an E. coli host system and package ssRNA during the expression process. Recently, we have engineered CCMV-VLPs by incorporating the universal tetanus toxin (TT) epitope at the N-terminus. The modified CCMV_TT-VLPs successfully form icosahedral particles T = 3, with a diameter of ~30 nm analogous to the parental VLPs. Interestingly, incorporating TT epitope at the C-terminus of CCMV_TT-VLPs results in the formation of Rod-shaped VLPs, ~1 μm in length and ~ 30 nm in width. In this study, we have investigated the draining kinetics and immunogenicity of both engineered forms (termed as Round-shaped CCMV_TT-VLPs and Rod-shaped CCMV_TT-VLPs) as potential B cell immunogens using different in vitro and in vivo assays. Our results reveal that Round-shaped CCMV_TT-VLPs are more efficient in draining to secondary lymphoid organs to charge professional antigen-presenting cells as well as B cells. Furthermore, compared to Rod-shaped CCMV_TT-VLPs, Round-shaped CCMV_TT-VLPs led to more than 100-fold increased systemic IgG and IgA responses accompanied by prominent formation of splenic germinal centers. Round-shaped CCMV_TT-VLPs could also polarize the induced T cell response toward Th1. To our knowledge, this is the first study investigating and comparing the draining kinetics and immunogenicity of one and the same VLP monomer forming nano-sized icosahedra or rods in the micrometer size.

Keywords: Cowpea chlorotic mottle virus; Humoral immune response; Virus-like particles.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibody Formation
Bromovirus*
Drainage
Epitopes
Escherichia coli
Vaccines, Virus-Like Particle*

Substances

Epitopes
Vaccines, Virus-Like Particle