Using Self-Assembling ADDomer Platform to Display B and T Epitopes of Type O Foot-and-Mouth Disease Virus

Abstract

Foot-and-mouth disease virus (FMDV) is a highly contagious and devastating virus that infects cloven-hoofed livestock and various wildlife species. Vaccination is the best measure to prevent FMD. ADDomer, as a kind of non-infectious adenovirus-inspired nanoparticle, has the advantage of high thermal stability. In this study, two dominant B-cell antigen epitopes (residues 129~160 and 200~213) and a dominant T-cell antigen epitope (residues 16~44) of type O FMDV were inserted into the ADDomer variable loop (VL) and arginine–glycine–aspartic acid (RGD) loop. The 3D structure of the recombinant protein (ADDomer-RBT) was simulated by homology modeling. First, the recombinant proteins were expressed by the baculovirus expression system and detected by western blot and Q Exactive mass spectrometry. Then the formation of VLPs was observed under a transmission electron micrograph (TEM). Finally, we evaluated the immunogenicity of chimeric VLPs with a murine model. Bioinformatic software analysis preliminarily corroborated that the chosen epitopes were successfully exposed on the surface of ADDomer VLPs. The TEM assay demonstrated the structural integrity of the VLPs. After immunizing, it was found that FMDV-specific antibodies can be produced in mice to induce humoral and cellular immune responses. To sum up, the ADDomer platform can be used as an effective antigen carrier to deliver antigen epitopes. This study presents one of the candidate vaccines to prevent and control FMDV.

Engineering the ADDobody protein scaffold for generation of high-avidity ADDomer super-binders

“…We and others have shown that a range of peptides and small protein domains can be inserted into the VL and RGD loops of the PBP 16,17,19,20,30 Chimera AH0 from our human Ad3 derived ADDobody-AH0 (Fig. 4A).…”

“…We and others have shown that a range of peptides and small protein domains can be inserted into the VL and RGD loops of the PBP 16,17,19,20,30 . Moving forward, based on our results, we can now conceivably generate a synthetic ADDobody library with randomized VL and RGD loops that can be used for ribosome display in vitro selection and evolution experiments against any target of choice.…”

“…, Chikungunya virus 16 or Type O foot-and-mouth disease 30 . Here, we engineered ADDobody in order to expand the scope of possible applications of the ADDomer nanoparticle, by converting it into a readily customizable, high-avidity super-binder against a target of choice.…”

“…The ADDomer nanoparticle has been used to develop vaccine candidates for diverse infectious diseases, displaying 60 and more B-cell and T-cell epitopes from SARS-CoV-2 17,20 , Chikungunya virus 16 or Type O foot-and-mouth disease 30 . Here, we engineered ADDobody in order to expand the scope of possible applications of the ADDomer nanoparticle, by converting it into a readily customizable, high-avidity super-binder against a target of choice.…”

Antibodies generatedin vitroandin vivoelucidate design of a thermostable ADDomer COVID-19 nasal nanoparticle vaccine

“…ADDomer was shown to drain to lymph nodes and is efficiently taken up by antigen presenting cells 28 . Successful presentation of T cell epitopes, in addition to B cell epitopes, by ADDomer has been demonstrated recently for Type O foot-and-mouth disease virus, resulting in protective responses against the viral pathogen 45 . A range of T cell epitopes in the SARS-CoV-2 proteome have been identified.…”