Immunogenicity of Multi-Target Chimeric RHDV Virus-Like Particles Delivering Foreign B-Cell Epitopes.

María Zamora-Ceballos,Juan Bárcena,David Gil-Cantero,José R Castón,Esther Blanco,Noelia Moreno

doi:10.3390/vaccines10020229

María Zamora-Ceballos, Juan Bárcena + Show 4 more

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https://doi.org/10.3390/vaccines10020229

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Abstract

The rabbit hemorrhagic disease virus (RHDV) vaccine platform is a nanoparticle composed of 180 copies of the viral capsid protein, VP60, self-assembled into virus-like particles (VLPs). RHDV VLPs are able to accept the simultaneous incorporation of target epitopes at different insertion sites. The resulting chimeric RHDV VLPs displaying immunogenic foreign antigens have been shown to induce specific protective immune responses against inserted heterologous T-cytotoxic and B-cell epitopes in the mouse and pig models. In this study, we explored whether RHDV-based engineered VLPs can be developed as efficient multivalent vaccines co-delivering different foreign B-cell antigens. We generated bivalent chimeric RHDV VLPs displaying two model B-cell epitopes at different surface-exposed insertion sites, as well as the corresponding monovalent chimeric VLPs. The immunogenic potential of the bivalent chimeric VLPs versus the monovalent constructs was assessed in the mouse model. We found that the bivalent chimeric VLPs elicited a strong and balanced antibody response towards the two target epitopes tested, although slight reductions were observed in the levels of specific serum antibody titers induced by bivalent chimeric VLPs as compared with the corresponding monovalent constructs. These results suggest that RHDV VLPs could represent a promising platform for the development of efficient multivalent vaccines.

Highlights

Virus-like particles (VLPs) are nanoparticles built from self-assembled proteins, usually viral capsid subunits, which mimic virion well-defined geometry, while being devoid of genetic material
Rabbit hemorrhagic disease virus (RHDV) virus-like particles (VLPs) represent a promising platform for multimeric antigen display [11–16] thanks to their intrinsic characteristics: (i) rabbit hemorrhagic disease virus (RHDV) VLPs are composed of a single capsid subunit, protein VP60, easing the production and engineering of chimeric VLPs; (ii) RHDV virions are relatively stable [17]; (iii) RHDV VLPs are highly immunogenic, inducing complete protection of rabbits against
Building on the RHDV VLP platform proof of concept, this study further explores a relevant issue: whether RHDV-based engineered VLPs can be developed as efficient multivalent vaccines co-delivering different foreign B-cell antigens

Summary

Introduction

Virus-like particles (VLPs) are nanoparticles built from self-assembled proteins, usually viral capsid subunits, which mimic virion well-defined geometry, while being devoid of genetic material. They are outstanding and safe immunogens combining a highly ordered and particulate nature with a lack of replication ability [1–4]. Besides their suitability as standalone vaccines for cognate viruses [5–7], genetically engineered VLPs are increasingly being explored as vaccine platforms for inducing immune responses against pathogenderived antigens of choice [8–10]. The distal P2 subdomain has a β-barrel core formed by β-sheets connected by seven loops (L1–L7) [21] (Figure 1c)

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