Host Immune Status and Response to Hepatitis E Virus Infection

Krain, Lisa J.; Nelson, Kenrad E.; Labrique, Alain

doi:10.1128/cmr.00062-13

Cited by 133 publications

(132 citation statements)

References 348 publications

(449 reference statements)

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“…Indeed, only a limited number of cases of transfusion-transmitted HEV have been reported despite administration of contaminated blood products (3,7,30,31). In addition, a recent retrospective survey of United Kingdom's plasma pool surprisingly showed that only one-half of HEV viremic Brit- HEV RNA-containing inocula derived from EDTA plasma (patients HEV0014 and HEV0122; n ϭ 4, respectively), a cryopreserved liver biopsy specimen (patient HEV0122; n ϭ 2), feces (patient HEV0069; n ϭ 2), or P7 culture supernatant of patient HEV0069 feces (n ϭ 7) (see Materials and Methods).…”

Section: Discussionmentioning

confidence: 99%

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Hepatitis E Virus (HEV) Genotype 3 Infection of Human Liver Chimeric Mice as a Model for Chronic HEV Infection

Garde

Pas

Net

et al. 2016

J Virol

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Genotype 3 (gt3) hepatitis E virus (HEV) infections are emerging in Western countries. Immunosuppressed patients are at risk of chronic HEV infection and progressive liver damage, but no adequate model system currently mimics this disease course. Here we explore the possibilities of in vivo HEV studies in a human liver chimeric mouse model (uPA ؉/؉ Nod-SCID-IL2R␥ ؊/؊ ) next to the A549 cell culture system, using HEV RNA-positive EDTA-plasma, feces, or liver biopsy specimens from 8 immunocompromised patients with chronic gt3 HEV. HEV from feces-or liver-derived inocula showed clear virus propagation within 2 weeks after inoculation onto A549 cells, compared to slow or no HEV propagation of HEV RNA-positive, EDTA-plasma samples. These in vitro HEV infectivity differences were mirrored in human-liver chimeric mice after intravenous (i.v.) inoculation of selected samples. HEV RNA levels of up to 8 log IU HEV RNA/gram were consistently present in 100% of chimeric mouse livers from week 2 to week 14 after inoculation with human feces-or liver-derived HEV. Feces and bile of infected mice contained moderate to large amounts of HEV RNA, while HEV viremia was low and inconsistently detected. Mouse-passaged HEV could subsequently be propagated for up to 100 days in vitro. In contrast, cell culture-derived or seronegative EDTA-plasma-derived HEV was not infectious in inoculated animals. In conclusion, the infectivity of feces-derived human HEV is higher than that of EDTA-plasma-derived HEV both in vitro and in vivo. Persistent HEV gt3 infections in chimeric mice show preferential viral shedding toward mouse bile and feces, paralleling the course of infection in humans. H epatitis E virus (HEV) is a nonenveloped positive-sense single-stranded RNA virus of the genus Orthohepevirus and family Hepeviridae (1). Four major HEV genotypes infecting humans have been described so far. Genotype 1 (gt1) and gt2 strains are isolated only from humans, whereas gt3 and gt4 strains are considered zoonotic viruses, present in both humans and several other species like pigs and wild game. HEV is spread through the oral-fecal route via contaminated water in developing countries or, among other routes, via direct contact with animals or the consumption of undercooked meat in industrialized countries. In immunocompetent individuals, HEV infection is mainly self-limiting and often asymptomatic and thus remains largely underdiagnosed. HEV infections in immunosuppressed patients, such as solid-organ transplant recipients, often persist and can progress quickly to liver fibrosis and cirrhosis (2-4).HEV gt3 infections are emerging in Western countries, including France, the United Kingdom, and the Netherlands (5-7). Despite an overall decrease in anti-HEV seroprevalence from 1996 to 2011, young adult blood donors demonstrated higher seroprevalences from 2000 to 2011 (8, 9). In addition, HEV RNA-positive blood donations were reported to increase in the Netherlands since 2012 (10). Although the exact source of this HEV gt3 infection is unknown,...

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Section: Discussionmentioning

confidence: 99%

“…In immunocompetent individuals, HEV infection is mainly self-limiting and often asymptomatic and thus remains largely underdiagnosed. HEV infections in immunosuppressed patients, such as solid-organ transplant recipients, often persist and can progress quickly to liver fibrosis and cirrhosis (2)(3)(4).…”

mentioning

confidence: 99%

Hepatitis E Virus (HEV) Genotype 3 Infection of Human Liver Chimeric Mice as a Model for Chronic HEV Infection

Garde

Pas

Net

et al. 2016

J Virol

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“…Patients with underlying liver disease and patients who are immunosuppressed or immunocompromised are at particular risk. 2 HEV is a non-enveloped, single-stranded, positive-sense RNA virus. It is the only member of the genus Hepevirus in the family Hepeviridae.…”

Section: Introductionmentioning

confidence: 99%

The development of a recombinant hepatitis E vaccine HEV 239

Zhao

et al. 2015

Human Vaccines & Immunotherapeutics

101

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Hepatitis E virus (HEV) infection is one of the main causes of acute hepatitis worldwide. A recombinant hepatitis E vaccine, HEV 239, has been licensed in China for immunizing adults of 16 y old and above. The vaccine antigen contains pORF2 aa 368 -606 of the HEV genotype 1 expressed in E. coli. The quality of the vaccine is controlled through a combination of biophysical, biochemical and immunochemical methods. The vaccine is well tolerated in adults. The efficacy of the HEV 239 vaccine against symptomatic and asymptomatic infection had been proven to be high during a Phase III clinical trial and long-term follow up. The safety and efficacy of HEV 239 vaccine in certain high-risk populations remains to be further investigated.

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“…5,6 7 The largest randomized, controlled phase III vaccine trials to date using this recombinant vaccine was conducted in Jiangsu Province, China, and enrolled 112,604 healthy adult participants. [8][9][10] A vaccine efficacy of approximately 79.2% (95% confidence interval [CI], 67.7% to 86.6%) in the prevention of infection was demonstrated with greater protection rate against clinical illness. 10,11 Another HEV vaccine based on recombinant HEV viral capsid protein was also tested clinically, demonstrating high efficacy against HEV infection and disease.…”

Section: Introductionmentioning

confidence: 99%

“…[8][9][10] A vaccine efficacy of approximately 79.2% (95% confidence interval [CI], 67.7% to 86.6%) in the prevention of infection was demonstrated with greater protection rate against clinical illness. 10,11 Another HEV vaccine based on recombinant HEV viral capsid protein was also tested clinically, demonstrating high efficacy against HEV infection and disease. 12, 13 14 The above-mentioned Hecolin Ò contains aluminum-based adjuvants for enhancing the antigen immunogenicity.…”

Section: Introductionmentioning

confidence: 99%

Comparable quality attributes of hepatitis E vaccine antigen with and without adjuvant adsorption-dissolution treatment

Zhang

Yang

et al. 2015

Human Vaccines & Immunotherapeutics

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Most vaccines require adjuvants for antigen stabilization and immune potentiation. Aluminum-based adjuvants are the most widely used adjuvants for human vaccines. Previous reports demonstrated the preservation of antigen conformation and other antigen characteristics after recovery from adjuvanted Hepatitis B and human papillomavirus vaccines. In this study, we used a combination of various physiochemical and immunochemical methods to analyze hepatitis E vaccine antigen quality attributes after recovery from adjuvants. All biochemical and biophysical methods showed similar characteristics of the p239 protein after recovery from adjuvanted vaccine formulation compared to the antigen in solution which never experienced adsorption/desorption process. Most importantly, we demonstrated full preservation of key antigen epitopes post-recovery from adjuvanted vaccine using a panel of murine monoclonal antibodies as exquisite probes. Antigenicity of p239 was probed with a panel of 9 mAbs using competition/blocking ELISA, surface plasmon resonance and sandwich ELISA methods. These multifaceted analyses demonstrated the preservation of antigen key epitopes and comparable protein thermal stability when adsorbed on adjuvants or of the recovered antigen post-dissolution treatment. A better understanding of the antigen conformation in adjuvanted vaccine will enhanced our knowledge of antigen-adjuvant interactions and facilitate an improved process control and development of stable vaccine formulation.

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Host Immune Status and Response to Hepatitis E Virus Infection

Cited by 133 publications

References 348 publications

Hepatitis E Virus (HEV) Genotype 3 Infection of Human Liver Chimeric Mice as a Model for Chronic HEV Infection

Hepatitis E Virus (HEV) Genotype 3 Infection of Human Liver Chimeric Mice as a Model for Chronic HEV Infection

The development of a recombinant hepatitis E vaccine HEV 239

Comparable quality attributes of hepatitis E vaccine antigen with and without adjuvant adsorption-dissolution treatment

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