A bacterially expressed particulate hepatitis E vaccine: antigenicity, immunogenicity and protectivity on primates

Li, Shao W.; Zhang, Jun; Li, Yi M.; Ou, Shan H.; Huang, Guo Y.; He, Zhi; Ge, Sheng; Xian, Yang; Pang, Shu Q.; Ng, Mun Hon; Xia, Ning

doi:10.1016/j.vaccine.2004.11.064

Cited by 221 publications

(205 citation statements)

References 15 publications

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“…We found that 8G12 reacted only with dimeric E2, but not with monomeric E2, while the previously known mAb 16D7 reacted with both monomeric and dimeric E2 [19] ( Figure 1A). The western blotting confirmed that 8G12 recognized the dimeric E2 of all four HEV genotypes, without any discrimination.…”

Section: Identification Of Mab 8g12 and Its Cross-genotype Neutralizasupporting

confidence: 48%

Structural basis for the neutralization of hepatitis E virus by a cross-genotype antibody

Tang

Zhang

et al. 2015

Cell Res

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Hepatitis E virus (HEV), a non-enveloped, positive-sense, single-stranded RNA virus, is a major cause of enteric hepatitis. Classified into the family Hepeviridae, HEV comprises four genotypes (genotypes 1-4), which belong to a single serotype. We describe a monoclonal antibody (mAb), 8G12, which equally recognizes all four genotypes of HEV, with ~2.53-3.45 nM binding affinity. The mAb 8G12 has a protective, neutralizing capacity, which can significantly block virus infection in host cells. Animal studies with genotypes 1, 3 and 4 confirmed the cross-genotype neutralizing capacity of 8G12 and its effective prevention of hepatitis E disease. The complex crystal structures of 8G12 with the HEV E2s domain (the most protruded region of the virus capsid) of the abundant genotypes 1 and 4 were determined at 4.0 and 2.3 Å resolution, respectively. These structures revealed that 8G12 recognizes both genotypes through the epitopes in the E2s dimerization region. Structure-based mutagenesis and cell-model assays with virus-like particles identified several conserved residues (Glu549, Lys554 and Gly591) that are essential for 8G12 neutralization. Moreover, the epitope of 8G12 is identified as a key epitope involved in virus-host interactions. These findings will help develop a common strategy for the prevention of the most abundant form of HEV infection.

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Section: Identification Of Mab 8g12 and Its Cross-genotype Neutralizasupporting

confidence: 48%

Structural basis for the neutralization of hepatitis E virus by a cross-genotype antibody

Tang

Zhang

et al. 2015

Cell Res

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“…8 Isoelectric point (pI) determination The whole column imaging method of capillary isoelectric focusing (iCIEF) was used to demonstrate the isoelectric point (pI) of the p239 VLPs. The operating system and reagents were all provided by the vendor (Advanced Electrophoresis Solutions Ltd, Ontario, Canada).…”

Section: High Performance Size-exclusion Chromatography (Hpsec)mentioning

confidence: 99%

“…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%

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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“…The People's Republic of China has recently developed a vaccine, HEV 239, which is expressed in Escherichia coli and occurs as a virus-like particles of 23nm in diameter. It is a 26-kDa protein encoded by ORF2 of HEV vaccine [41]. In a phase II study piloted among seronegative adults, the vaccine was found to be safe, immunogenic, and provided protection against HEV infection with an efficacy of 83% [42].…”

Section: Introductionmentioning

confidence: 99%

Hepatitis E – A new era in understanding

Krzowska-Firych

Lucas²,

Lucas³

et al. 2018

Ann Agric Environ Med.

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Hepatitis E virus [HEV], the last of the five hepatotropic viruses to be discovered, was originally considered to cause an acute, travel-associated self-limiting illness restricted to humans; however, new research shows that there are animal reservoirs and zoonotic transmission. Additionally, HEV is now considered as a major health burden worldwide, leading to significant morbidity and mortality; therefore, the topic of hepatitis E is of re-emerging importance, having brought to light important questions such as the transmission of HEV, especially in developed countries, as well as treatment and vaccination options. HEV belongs to the genus Hepevirus in the Hepeviridae family. The HEV genome sequence is relatively stable; however, there is a diversity of genotypes which are helpful in comprehending the epidemiological phenomena. HEV is classified based on the nucleotide sequences of the genome and is now characterised as a single serotype with four major genotypes . Hepatitis E cases are not clinically distinguishable from other types of acute viral hepatitis, although diagnosis can be strongly suspected in certain epidemiological settings. It is imperative to raise awareness among physicians about the importance of HEV, with the aim of helping recognise, prevent and treat HEV infections. This review article highlights the current developments of HEV in microbiology, epidemiology, clinical features, treatment and prophylaxis.

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A bacterially expressed particulate hepatitis E vaccine: antigenicity, immunogenicity and protectivity on primates

Cited by 221 publications

References 15 publications

Structural basis for the neutralization of hepatitis E virus by a cross-genotype antibody

Structural basis for the neutralization of hepatitis E virus by a cross-genotype antibody

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

Hepatitis E – A new era in understanding

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