Chimeric RHDV Virus-Like Particles Displaying Foot-and-Mouth Disease Virus Epitopes Elicit Neutralizing Antibodies and Confer Partial Protection in Pigs

22 Pág. Centro de Investigación en Sanidad Animal (CISA)
Currently there is a clear trend towards the establishment of virus-like particles (VLPs) as a powerful tool for vaccine development. VLPs are tunable nanoparticles that can be engineered to be used as platforms for multimeric display of foreign antigens. We have previously reported that VLPs derived from rabbit hemorrhagic disease virus (RHDV) constitute an excellent vaccine vector, capable of inducing specific protective immune responses against inserted heterologous T-cytotoxic and B-cell epitopes. Here, we evaluate the ability of chimeric RHDV VLPs to elicit immune response and protection against Foot-and-Mouth disease virus (FMDV), one of the most devastating livestock diseases. For this purpose, we generated a set of chimeric VLPs containing two FMDV-derived epitopes: a neutralizing B-cell epitope (VP1 (140-158)) and a T-cell epitope [3A (21-35)]. The epitopes were inserted joined or individually at two different locations within the RHDV capsid protein. The immunogenicity and protection potential of the chimeric VLPs were analyzed in the mouse and pig models. Herein we show that the RHDV engineered VLPs displaying FMDV-derived epitopes elicit a robust neutralizing immune response in mice and pigs, affording partial clinical protection against an FMDV challenge in pigs.
This work was supported by Spanish Ministry of Science and Innovation (grants AGL2016-76445-R to EB and AA; PID2019-107145RB-I00 to EB and BFU2017-88736- to JRC) and Comunidad de Madrid co-financed with ECFEDER funds (P2018/BAA-4370 PLATESA 2 to EB and P2018/NMT-4389 to JRC). GR and NM were holders of a PhD fellowship from the Spanish Ministry of Science and Innovation (FPI programme) and CPM was a PhD fellow of the La Caixa Foundation International Fellowship Program (La Caixa/CNB).