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

Abstract

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.

An Adenovirus Vector Expressing FMDV RNA Polymerase Combined with a Chimeric VLP Harboring a Neutralizing Epitope as a Prime Boost Strategy to Induce FMDV-Specific Humoral and Cellular Responses

“…Because 1C9 is directed against a conformational epitope affected by insertion of chimeric sequences into the exposed VP60 loop [ 38 ], we interpret this result to show that insertion of both the control and the relevant epitopes occurred as expected. Altogether, these results extend previous reports [ 10 , 13 ] to show insertion of a new antigenic peptide at the exposed loop of RHDV VP60 for the generation of chimeric VLPs and confirms the FMDV serotype C specificity of these novel particles.…”

“…We recently reported that a chimeric RHDV VLP vaccine candidate containing the FMDV B-cell epitope from O UK/01 serotype as immunogen induces a potent humoral response both in murine and porcine models. Further, vaccination of pigs induced high titers of neutralizing antibodies and conferred partial protection upon homologous challenge [ 10 ].…”

“…As a control, baculoviruses expressing VP60 without foreign epitope or with the equivalent epitope from FMDV serotype O (VP60_OUK) were used in parallel. The recombinant proteins were purified following previously established VLP obtention protocols [ 10 ] and Western blot analyses using anti-VP60 and anti FMDV_CS8c1 peptide (SD6) antibodies confirmed the presence of the expected epitope sequence in the chimeric particle ( Figure 3 A). The purified particles were then analyzed by ELISA using the SD6 antibody to confirm the presence of the newly inserted peptide sequence ( Figure 3 B).…”

“…Important efforts have been devoted to the development of safer and broadly neutralizing vaccines in the recent years including the generation of attenuated viruses, subunit vaccines, empty stabilized virus-like particles (VLPs), and others. Recently, we have employed modified VLPs to induce specific neutralizing antibody responses as well as partial protection against FMDV serotype-O-caused disease in swine [ 10 ]. To this end, we used the well-characterized VP60 protein from rabbit hemorrhagic disease virus (RHDV) which can self-assemble into highly stable approximately 40 nm diameter VLPs when expressed from recombinant baculoviruses [ 11 ].…”

“…These particles were found to induce high FMDV-neutralizing antibody titers both in a murine and a porcine model. However, failure to induce complete protection against a homologous challenge in swine was attributed in part to an observed lack of specific T-cell responses, even when chimeric VLPs bearing an FMDV T-cell epitope were used [ 10 ].…”