Protection against hepatitis E virus infection by naturally acquired and vaccine-induced immunity

Zhang, J.; Zhang, X.-F.; Zhou, Cheng; Wang, Z.-Z.; Huang, Shou-Jie; Yao, Xin; Liang, Zhenglun; Wu, Ting; Li, J.-X.; Yan, Qiang; Yang, Chang‐Lin; Jiang, Han-Min; Huang, Hong-Jiang; Xian, Yang-Ling; Shih, J. W.-K.; Ng, Mun‐Hon; Li, Yuewen; Wang, J.-Z.; Zhu, Fengcai; Xia, Ningshao

doi:10.1111/1469-0691.12419

Cited by 72 publications

(74 citation statements)

References 25 publications

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“…However, subclinical HEV infection subsequent to vaccination has been demonstrated in monkeys in several preclinical trials (225)(226)(227)(228)(229)(230) and more recently confirmed in follow-up of humans participating in the large recombinant vaccine trial in Jiangsu, China (231). The duration of protection from clinical disease remains unknown, and optimal dosing and booster schedules remain to be determined.…”

Section: Protective Immunity Following Vaccinationmentioning

confidence: 99%

“…The research team identified asymptomatic infections through serosurveillance, defining a case as an individual with a 4-fold increase in anti-HEV IgG level in serial samples. Clinical cases were detected through an algorithm of symptom surveillance plus laboratory confirmation, testing those with fatigue or loss of appetite for elevated ALT and then demonstrating the presence of HEV RNA, anti-HEV IgM, or a 4-fold increase in anti-HEV IgG titer (231). Three clinical cases and 112 subclinical infections were detected in the placebo group during the extended follow-up period using this combination of surveillance strategies, while 24 asymptomatic infections were recorded in the vaccinated group.…”

Section: Protective Immunity Following Vaccinationmentioning

confidence: 99%

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Host Immune Status and Response to Hepatitis E Virus Infection

2014

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SUMMARY Hepatitis E virus (HEV), identified over 30 years ago, remains a serious threat to life, health, and productivity in developing countries where access to clean water is limited. Recognition that HEV also circulates as a zoonotic and food-borne pathogen in developed countries is more recent. Even without treatment, most cases of HEV-related acute viral hepatitis (with or without jaundice) resolve within 1 to 2 months. However, HEV sometimes leads to acute liver failure, chronic infection, or extrahepatic symptoms. The mechanisms of pathogenesis appear to be substantially immune mediated. This review covers the epidemiology of HEV infection worldwide, the humoral and cellular immune responses to HEV, and the persistence and protection of antibodies produced in response to both natural infection and vaccines. We focus on the contributions of altered immune states (associated with pregnancy, human immunodeficiency virus [HIV], and immunosuppressive agents used in cancer and transplant medicine) to the elevated risks of chronic infection (in immunosuppressed/immunocompromised patients) and acute liver failure and mortality (among pregnant women). We conclude by discussing outstanding questions about the immune response to HEV and interactions with hormones and comorbid conditions. These questions take on heightened importance now that a vaccine is available.

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Section: Protective Immunity Following Vaccinationmentioning

confidence: 99%

Section: Protective Immunity Following Vaccinationmentioning

confidence: 99%

Host Immune Status and Response to Hepatitis E Virus Infection

2014

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“…However, follow-up data indicate that HEV infections can still occur among vaccinated adults, 111 and only incidental data on safety and efficacy in pregnant women are available. 112 Evaluating the effectiveness of these vaccines in preventing maternal disease and death and reducing the burden of fetal loss, premature delivery, and neonatal morbidity and mortality should stand among global maternalchild health priorities.…”

Section: Challenges In Understanding Mother-to-child Transmission Of Hevmentioning

confidence: 99%

Fetal and Neonatal Health Consequences of Vertically Transmitted Hepatitis E Virus Infection

Krain

Atwell

Nelson

et al. 2014

The American Journal of Tropical Medicine and Hygiene

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Abstract. Hepatitis E virus (HEV) infections lead to tens of thousands of deaths annually, mostly in developing countries. Hepatitis E poses a significant threat to the health of expectant mothers, a well-noted epidemiologic feature of the disease, but the contribution of vertically transmitted HEV infection to fetal and neonatal morbidity and mortality has received limited attention. Evidence assembled to date suggests that mother-to-child HEV transmission may be frequent and deleterious to the fetus and newborn in pregnancies affected by hepatitis E. Additional work is required to resolve key questions. (1) What risks do subclinical maternal HEV infections and infections early in pregnancy pose to fetal health and development? (2) Does vertical transmission occur during labor and/or breastfeeding and contribute appreciably to neonatal morbidity and mortality? (3) How do treatment decisions for severely ill mothers affect fetal and neonatal outcomes? (4) Can maternal vaccination effectively prevent vertical transmission of HEV?

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“…The specificity of HEV-VLP binding and entry into the liver cells was demonstrated using reporter linked fluorescent VLP's [1]. Similar bacterially generated VLPs (HEV 239) have been licensed as a potential candidate vaccine (Hecolin) against HEV in China [2][3][4].…”

Section: Resultsmentioning

confidence: 99%

Recombinant Hepatitis E virus like particles can function as RNA nanocarriers

Panda¹,

Kapur²,

Paliwal³

et al. 2016

Nano Online

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Background: Assembled virus-like particles (VLPs) without genetic material, with structure similar to infectious virions, have been successfully used as vaccines. We earlier described in vitro assembly, characterisation and tissue specific receptor dependent Clathrin mediated entry of empty HEV VLPs, produced from Escherichia coli expressed HEV capsid protein (pORF2). Similar VLP's have been described as a potential candidate vaccine (Hecolin) against HEV. Findings:We have attempted to use such recombinant assembled Hepatitis E virus (HEV) VLPs as a carrier for heterologous RNA with protein coding sequence fused in-frame with HEV 5′ region (containing cap and encapsidation signal) and investigated, if the relevant protein could be expressed and elicit an immune response in vivo. In vitro transcribed red fluorescent protein (RFP)/Hepatitis B virus surface antigen (HBsAg) RNA, fused to 5′-HEV sequence with cap and encapsidation signal (1-249 nt), was packaged into the recombinant HEV-VLPs and incubated with five different cell lines (Huh7, A549, Vero, HeLa and SiHa). The pORF2-VLPs could specifically transfer exogenous coding RNA into Huh7 and A549 cells. In vivo, Balb/c mice were immunized (intramuscular injections) with 100 µg pORF2-VLP encapsidated with 5′-methyl-G-HEV (1-249 nt)-HBsAg RNA, blood samples were collected and screened by ELISA for anti-pORF2 and anti-HBsAg antibodies. Humoral immune response could be elicited in Balb/c mice against both HEV capsid protein and cargo RNA encoded HBsAg protein. Conclusions:These findings suggest that other than being a possible vaccine, HEV pORF2-VLPs can be used as a promising non-replicative tissue specific gene delivery system. FindingsVLPs inherit most of the properties of parent virus, like capability of self-assembly into organised structure, specific interaction with nucleic acid/protein, and cell-specific entry. These replication-deficient, non-infectious, nano-structured particles can be useful if they can effectively deliver therapeutically useful nucleic acid, drug, targeting peptide or a conjugated imaging molecule.We had described generation of HEV VLP's from Escherichia coli produced capsid protein Here, we investigate whether (1) empty VLPs of HEV could encapsidate heterologous RNA fused with encapsidation signal and deliver the exogenous RNA in a cell specific manner as a nanocarrier? (2) Can the foreign gene be translated from delivered chimeric RNA? and (3) If injected to animals, can the RNA-VLP complex induce immunity to both the carrier HEV capsid protein and the protein expressed from delivered RNA? To study the above possibilities, we generated a chimeric RNA where reporter/antigen producing gene/coding sequence (RFP/

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Protection against hepatitis E virus infection by naturally acquired and vaccine-induced immunity

Cited by 72 publications

References 25 publications

Host Immune Status and Response to Hepatitis E Virus Infection

Host Immune Status and Response to Hepatitis E Virus Infection

Fetal and Neonatal Health Consequences of Vertically Transmitted Hepatitis E Virus Infection

Recombinant Hepatitis E virus like particles can function as RNA nanocarriers

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