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

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.

Characterization of hepatitis E virus natural infection in farmed rabbits

“…A study demonstrated that the newborn rabbits delivered by HEV-infected pregnant rabbits showed HEV infection, which indicated vertical transmission of HEV. 31 In modern breeding facilities, rabbits are usually caged individually and separated from their excretions. Therefore, vertical transmission of HEV3-ra in farmed rabbits cannot be ruled out.…”

Infectivity and pathogenicity of different hepatitis E virus genotypes/subtypes in rabbit model

“…However, 60% (3/5) of the inoculated rabbits seroconverted to anti-HEV at the end of the study indicating inapparent infection. We previously found that this hHEV-3 strain could induce robust infection in pregnant rabbits [ 32 ]. This observation may be explained by the different host immune status during pregnancy, which increased the host susceptibility to certain pathogens and increased disease severity [ 41 ].…”

“…Serum and fecal samples were collected weekly for two consecutive weeks to test alanine aminotransferase (ALT) for establishing the baselines. All samples were negative for anti-HEV antibodies by an enzyme-linked immunosorbent assay (ELISA) and HEV RNA by a previously described reverse transcription-nested polymerase chain reaction (RT-nPCR) [ 32 ].…”

“…Total RNA was extracted from 100 μL of serum or fecal suspensions prepared as above using TRIzol reagent (Invitrogen, Burlington, ON, Canada) following a standard instruction. The RNA was then amplified by RT-nPCR for partial ORF2 genome on an automatic PCR system (Applied Biosystems ProFlex PCR, USA) and HEV viral load was determined using a commercial one-step real-time quantitative PCR assay (GoTaq® Probe 1-step RT-qPCR System Kit, Promega, Wisconsin, USA), as previously described [ 32 ].…”

Hepatitis E virus infection during pregnancy

“…HEV 239 also seems to be safe in pregnant women [143]. In addition, in a rabbit model, two doses of 10 μg or 5 μg HEV 239 vaccine administered intramuscularly on weeks 0 and 4 not only serve to protect pregnant rabbits from HEV infection but also prevent HEV-related adverse outcomes [144]. Although the safety and efficacy of this vaccine in a large population of pregnant women remain to be determined, this vaccine is promising for HEV infection prevention in pregnancy and may thus decrease HEV-associated morbidity and mortality.…”