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Review
. 2018 Feb 19:9:266.
doi: 10.3389/fmicb.2018.00266. eCollection 2018.

Vaccine Development against Zoonotic Hepatitis E Virus: Open Questions and Remaining Challenges

Yuchen Nan  1   2 , Chunyan Wu  1   2 , Qin Zhao  1   2 , Yani Sun  1   2 , Yan-Jin Zhang  3 , En-Min Zhou  1   2
Affiliations
Review

Vaccine Development against Zoonotic Hepatitis E Virus: Open Questions and Remaining Challenges

Yuchen Nan et al. Front Microbiol. .

Abstract

Hepatitis E virus (HEV) is a fecal-orally transmitted foodborne viral pathogen that causes acute hepatitis in humans and is responsible for hepatitis E outbreaks worldwide. Since the discovery of HEV as a zoonotic agent, this virus has been isolated from a variety of hosts with an ever-expanding host range. Recently, a subunit HEV vaccine developed for the prevention of human disease was approved in China, but is not yet available to the rest of the world. Meanwhile, notable progress and knowledge has been made and revealed in recent years to better understand HEV biology and infection, including discoveries of quasi-enveloped HEV virions and of a new function of the HEV-ORF3 product. However, the impact of these new findings on the development of a protective vaccine against zoonotic HEV infection requires further discussion. In this review, hallmark characteristics of HEV zoonosis, the history of HEV vaccine development, and recent discoveries in HEV virology are described. Moreover, special attention is focused on quasi-enveloped HEV virions and the potential role of the HEV-ORF3 product as antibody-neutralization target on the surface of quasi-enveloped HEV virions to provide new insights for the future development of improved vaccines against zoonotic HEV infection.

Keywords: HEV vaccine; HEV-ORF3 product; hepatitis E virus; quasi-enveloped virion; subunit vaccine; zoonosis.

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Figures

FIGURE 1
FIGURE 1
Schematic illustration of HEV-ORF2 protein domains.
FIGURE 2
FIGURE 2
Schematic illustration of non-enveloped and quasi-enveloped HEV particles as well as enveloped virus. The putative model of quasi-enveloped HEV virion includes ORF3 product in its envelope as the existence of pORF3 has been confirmed by capturing quasi-enveloped HEV virion with anti-pORF3 antibodies and further supported by prediction of a putative transmembrane region in the N-terminal of pORF3.
FIGURE 3
FIGURE 3
Alignment of amino acid sequence of pORF3 of four HEV genotypes. Genotype 1 (GT-1) (GenBank accession number AF444002), GT-2 (accession number M74506), GT-3 (accession number HQ709170), and GT-4 (accession number AB074915). “⋅” represent those residues that are the same as consensus sequence.
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