The impact of size on particle drainage dynamics and antibody response

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 other innate humoral immune components. VLPs derived from the plant Bromovirus genus, specifically cowpea chlorotic mottle virus (CCMV), are T=3 icosahedron particles. They 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 toxoid (TT) epitope at the N-terminus. The modified CCMVTT-VLPs successfully form icosahedral particles T=3, with a diameter of ∼30nm analogous to the parental VLPs. Interestingly, incorporating TT epitope at the C-terminus of CCMVTT-VLPs results in the formation of Rod-shaped VLPs, ∼1µm in length and ∼30nm in width. In this study, we have investigated the draining kinetics and immunogenicity of both engineered forms (termed as Round-shaped CCMVTT-VLPs and Rod-shaped CCMVTT-VLPs) as potential B cell immunogens using different in vitro and in vivo assays. Our results reveal that Round-shaped CCMVTT-VLPs are more efficient in draining to secondary lymphoid organs to charge antigen-presenting cells as well as B-cells. Furthermore, compared to Rod-shaped CCMVTT-VLPs, Round-shaped CCMVTT-VLPs led to more than 100-fold increased systemic IgG and IgA responses accompanied by prominent formation of splenic germinal centers. Round-shaped CCMVTT-VLPs could also polarize the induced immune response towards TH1. Up 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 icosahedrons or rods in the micrometer size.

A scalable and highly immunogenic virus-like particle-based vaccine against SARS-CoV-2

“…Furthermore, incorporating the whole RBD domain into CuMV TT did not allow the formation of VLPs most likely due to steric constraints. The used genetic fusion technique in this study facilitated the assembly ofT=3 icosahedral VLPs which is essential for effective induction of a humoral immune response (13). Using this technique, we have recently developed a vaccine against MERS-CoV by incorporating the RBM domain into CuMV TT .…”

“…Virus-like particles (VLPs) represent one of the conventional vaccine platforms in the sense that there are globally marketed products (e.g., HBV and HPV vaccines) that that have demonstrated the clinical usefulness of this modality. VLPs consist of viral structural proteins that upon recombinant expression, self-assemble into particles with a mostly icosahedrons and rarely helical symmetry (13). Recently, we have developed an immunologically optimized VLP platform based on the cucumber mosaic virus (CuMV TT -VLPs) (14).…”

AP205 VLPs Based on Dimerized Capsid Proteins Accommodate RBM Domain of SARS-CoV-2 and Serve as an Attractive Vaccine Candidate

“…Virus-like particles (VLPs) represent one of the relatively traditional vaccine platforms in the sense that they have already proven their clinical usefulness. VLPs consist of viral structural proteins that upon recombinant expression, self-assemble into particles, mostly icosahedrons and rarely helical [ 9 ]. We have previously described the favorable characteristics of VLPs and the reason they constitute a good vaccine template and have given rise to highly successful vaccines [ 10 , 11 , 12 ].…”

Neutralization of MERS coronavirus through a scalable nanoparticle vaccine

“…Furthermore, our newly developed vaccine platform is selfadjuvanted with prokaryotic ssRNA which is packaged within VLPs during the expression and assembly process in E. coli. The selfpackaged adjuvant serves as TLR7/8 ligand and promotes the activation of antigen-presenting cells (APCs) and B cells [22][23][24][25] .…”

“…coli. The self-packaged adjuvant serves as TLR7/8 ligand and promotes the activation of antigen-presenting cells (APCs) and B cells 22 – 25 .…”