Abstract
BackgroundZoonotic 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.ResultsFirst, 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.ConclusionThis 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.
Highlights
Zoonotic hepatitis E virus (HEV) infection emerged as a serious threat in the industrialized countries
Only the HEV genotypes 1 and 2 infections would be targeted in those special cases, while the zoonotic hepatitis E would continue to circulate in the non-endemic areas, not because the vaccine is ineffective against zoonotic genotypes but only because the use of hepatitis E vaccine is not implemented in the immunization programs in these non-endemic regions
Since swine is the main host of zoonotic HEV [3, 5], the control of HEV in swine will permit the prevention of HEV spread to humans
Summary
Zoonotic hepatitis E virus (HEV) infection emerged as a serious threat in the industrialized countries. World Health Organization does not recommend the introduction of the HEV vaccine in national immunization programs except in special situations such as outbreaks where the risk of hepatitis E or its complications/mortality is high [9]. The most notable illustration is the effort for the control and the eradication of rabies through the removal of stray dogs, quarantine of incoming pets, and most importantly vaccination of domestic animals [10] Likewise, this same approach would be of great public health interest, concerning zoonotic HEV infection. Since swine is the main host of zoonotic HEV (genotype 3 and 4) [3, 5], the control of HEV in swine will permit the prevention of HEV spread to humans When it occurs in swine, hepatitis E infection is usually asymptomatic and self-limiting. The infection spreads rapidly through susceptible animal populations and can lead to large-scale epidemics with detrimental economic consequences [11]. (2) Given the severity of the FMDV infection and its outcomes, vaccination against FMDV is mandatory in China, among many other countries [11]
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