Design and development of a chimeric vaccine candidate against zoonotic hepatitis E and foot-and-mouth disease

Abstract

Background Zoonotic hepatitis E virus (HEV) infection emerged as a serious threat in the industrialized countries. The aim of this study is exploring a new approach for the control of zoonotic HEV in its main host (swine) through the design and development of an economically interesting chimeric vaccine against HEV and against a devastating swine infection: the foot-and-mouth disease virus (FMDV) infection. Results First, we adopted a computational approach for rational and effective screening of the different HEV-FMDV chimeric proteins. Next, we further expressed and purified the selected chimeric immunogens in Escherichia coli ( E. coli ) using molecular cloning techniques. Finally, we assessed the antigenicity and immunogenicity profiles of the chimeric vaccine candidates. Following this methodology, we designed and successfully produced an HEV-FMDV chimeric vaccine candidate (Seq 8-P222) that was highly over-expressed in E. coli as a soluble protein and could self-assemble into virus-like particles. Moreover, the vaccine candidate was thermo-stable and exhibited optimal antigenicity and immunogenicity properties. Conclusion This study provides new insights into the vaccine development technology by using bioinformatics for the selection of the best candidates from larger sets prior to experimentation. It also presents the first HEV-FMDV chimeric protein produced in E. coli as a promising chimeric vaccine candidate that could participate in reducing the transmission of zoonotic HEV to humans while preventing the highly contagious foot-and-mouth disease in swine.

Identifying Circular RNAs in HepG2 Expressing Genotype IV Swine Hepatitis E Virus ORF3 Via Whole Genome Sequencing

“…Lipid metabolism disorder will cause jaundice, which is the typical clinical symptoms of swine hepatitis E. In HepG2 cells, we used bioinformatics methods for the first time to predict that there were hsa_circ_0002229, circRNA14701, hsa_circ_0093888, circRNA3581, circRNA3580, and circRNA3582 involved in triglyceride mobilization. When SHEV infection leads to jaundice, liver function is damaged and bile excretion is blocked, and lipid digestion, absorption and metabolism are affected 34 , 52 , 53 . The molecular mechanism of ORF3 affecting host lipid metabolism is not completely clear, we will further explore it.…”

The Re-Emergence of Hepatitis E Virus in Europe and Vaccine Development

“…Chimeric vaccines are composed of the immunogenic protein from two or more viruses, and they induce an immunogenic response against more than one disease. In recent years, HEV has been a part of dual-vaccination efforts against foot-and-mouth disease (FMDV) [ 261 ], hepatitis B virus (HBV) [ 262 ], porcine circovirus 2 (PCV2) [ 263 ], influenza virus [ 215 , 217 , 264 ], hepatitis A virus (HAV) [ 265 , 266 ], norovirus (NoV) and astrovirus (AstV) [ 267 ], and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [ 268 ]. The formation of chimeric proteins can vary based on the chosen host cell expression system, which is also the case in the formation of non-chimeric proteins.…”

“…E. coli is commonly involved in these protocols. E. coli was used in the formation of the first HEV-FMDV chimeric protein, where this chimeric protein exhibited the characteristics of water solubility and VLPs self-assembly [ 261 ]. The protein was included in a heat-stable vaccine candidate [ 261 ].…”

“…E. coli was used in the formation of the first HEV-FMDV chimeric protein, where this chimeric protein exhibited the characteristics of water solubility and VLPs self-assembly [ 261 ]. The protein was included in a heat-stable vaccine candidate [ 261 ]. Nicotiana benthamiana successfully expressed HBc-HEV chimeric protein, with spontaneous self-assembly into “ragged” VLPs.…”