Hepatitis E-related adverse pregnancy outcomes and their prevention by hepatitis E vaccine in a rabbit model

Lin Wang,Shuangshuang Li,Ling Wang,Zhaochao Liang,Qianhui Wang,Qiyu He,Manyu Li

doi:10.1080/22221751.2019.1643260

Lin Wang, Shuangshuang Li + Show 5 more

Open Access

https://doi.org/10.1080/22221751.2019.1643260

Copy DOI

Abstract

ABSTRACT Hepatitis E virus (HEV) can lead to high mortality during pregnancy. This study was to investigate the adverse pregnancy outcomes caused by different HEV genotypes and their prevention by HEV 239 vaccine in rabbits. Forty-two female rabbits were randomly and equally divided into 7 groups (A-G). HEV 239 vaccine and a placebo were administered to groups E (10 μg×2), F (5 μg×2) and G (1 mL of PBS×2) before copulation. After pregnancy, 1 mL of 1.5×106 copies/mL rabbit HEV3 was inoculated to groups A, E, F and G, swine HEV4/human HEV3 to groups B/C, and group D was a negative control. Anti-HEV antibody, HEV RNA, and alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels were monitored. Pregnant rabbits infected by HEV manifested HEV infection symptoms including fecal virus shedding, ALT/AST elevation, and histopathological changes, and adverse pregnancy outcomes. Immunized pregnant rabbits in groups E and F showed no HEV infection symptoms and adverse outcomes. The newborn rabbits delivered by pregnant rabbits with/without immunization showed without/with HEV infection symptoms. This study demonstrated that multiple genotypes of HEV infection can cause adverse outcomes and HEV 239 vaccine can prevent HEV-related adverse outcomes in pregnant rabbits.

Highlights

Hepatitis E virus (HEV) is the main cause of acute viral hepatitis in developing countries, which has aroused wide public concern [1,2,3]
HEV-related adverse pregnancy outcomes are caused by mainly HEV1 [10], and whether other genotypes of HEV can lead to adverse outcomes during pregnancy is still unclear
Studies have suggested that mainly HEV1 infection is associated with high mortality in pregnant women [10], there is limited research to investigate the influence of other HEV genotypes

Summary

Introduction

Hepatitis E virus (HEV) is the main cause of acute viral hepatitis in developing countries, which has aroused wide public concern [1,2,3]. In pregnant women, the mortality rate of HEV infection can reach as high as 25% [6,7,8,9]. To date, the mechanism of the high mortality rate of HEV infection in pregnant women remains unclear. We successfully established a HEV-infected pregnant rabbit model that can simulate the HEV-related high mortality rate observed in pregnant women [12]. This study aimed to investigate the pathogenicity of different HEV genotypes in pregnant rabbits and the efficacy of the HEV 239 vaccine in preventing adverse outcomes and vertical transmission of HEV infection in pregnant rabbits

Objectives

Methods

Results

Conclusion