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TitleAntibodies elicited by hepatitis E vaccination in humans confer cross-genus protection against rat hepatitis E virus.
Journal, issue, pagesJ Hepatol, Vol. 83, Issue 5, Page 1046-1056, Year 2025
Publish dateJun 24, 2025
AuthorsZihao Chen / Liqin Liu / Jianwen Situ / Guanghui Li / Shaoqi Guo / Qi Lai / Shusheng Wu / Yanan Jiang / Jingyan Fan / Zimin Tang / Yu Li / Guiping Wen / Siling Wang / Dong Ying / Yonghao Liang / Stanley Siu-Fung Ho / Xiaodan Ma / James Yiu-Hung Tsoi / Estie Hon-Kiu Shun / Nicholas Foo-Siong Chew / Weihui Ma / Weiwei Mao / Tingting Li / Zhenqin Chen / Mujin Fang / Yingbin Wang / Hai Yu / Fa Zhang / Anna Jinxia Zhang / Shaowei Li / Ningshao Xia / Siddharth Sridhar / Qingbing Zheng / Zizheng Zheng /
PubMed AbstractBACKGROUND & AIMS: Paslahepevirus balayani (bHEV), also known as hepatitis E virus (HEV), encompasses eight genotypes, five of which infect humans. Rats are natural reservoirs of Rocahepevirus ratti ...BACKGROUND & AIMS: Paslahepevirus balayani (bHEV), also known as hepatitis E virus (HEV), encompasses eight genotypes, five of which infect humans. Rats are natural reservoirs of Rocahepevirus ratti genotype 1 (HEV-r-1; rat HEV; rHEV), which has recently been implicated in viral hepatitis. Despite the antigenic divergence between bHEV and rHEV, studies on shared protective antibodies remain rare.
METHODS: Polyclonal and monoclonal antibody responses against bHEV and rHEV were analyzed using antibody enzyme-linked immunosorbent assays. The efficacy of six potent bHEV-elicited cross-reactive antibodies in preventing rHEV infection was evaluated via challenge assays in rats. Cryo-electron microscopy was performed to assess the structural basis for the differential protective efficacy of the six antibodies. The viral lysis ability of these antibodies was assessed by separately reacting purified HEV-b-1 and HEV-r-1 virions with each antibody.
RESULTS: We determined that antibody responses to bHEV infection and vaccination possess limited cross-reactivity to rHEV and identified two cross-reactive antigenic sites within the E2s domain. Structural analysis and animal challenge studies pinpointed potent cross-reactive antibodies targeting antigenic site 1, indicating its prophylactic efficacy against rHEV. Conversely, antibodies recognizing antigenic site 2 were found to facilitate viral lysis of bHEV but not rHEV.
CONCLUSIONS: These findings underscore the importance of antigenic site 1 in the design of broad-spectrum vaccines and therapeutics to mitigate the impact of diverse HEV genotypes on human health.
IMPACT AND IMPLICATIONS: Rat HEV (rHEV) spillover to humans represents an unprecedented threat. Significant antigenic differences between rHEV and bHEV (Paslahepevirus balayani) may exacerbate the impact of viral hepatitis. Our study reveals that cross-reactive human antibodies can offer protection against rHEV infection. Cross-protective antibodies targeting antigenic site 1 can be used to guide the development of practical strategies for preventing rHEV infection.
External linksJ Hepatol / PubMed:40571163
MethodsEM (single particle)
Resolution2.38 - 2.91 Å
Structure data

61503

9jie

EMDB-61503, PDB-9jie:
Rat hepatitis E virus capsid protein E2s domain in complex with Fab C6
Method: EM (single particle) / Resolution: 2.76 Å

61504

9jif

EMDB-61504, PDB-9jif:
Hepatitis E virus capsid protein E2s domain (genotype I) in complex with Fab C6
Method: EM (single particle) / Resolution: 2.79 Å

61505

9jig

EMDB-61505, PDB-9jig:
Hepatitis E virus capsid protein E2s domain (genotype IV) in complex with Fab C6
Method: EM (single particle) / Resolution: 2.38 Å

61506

9jii

EMDB-61506, PDB-9jii:
Rat hepatitis E virus capsid protein E2s domain in complex with Fab C158
Method: EM (single particle) / Resolution: 2.54 Å

61507

9jij

EMDB-61507, PDB-9jij:
Hepatitis E virus capsid protein E2s domain (genotype I) in complex with Fab C158
Method: EM (single particle) / Resolution: 2.64 Å

61508

9jik

EMDB-61508, PDB-9jik:
Rat hepatitis E virus capsid protein E2s domain in complex with Fab C127
Method: EM (single particle) / Resolution: 2.91 Å

61509

9jil

EMDB-61509, PDB-9jil:
Rat hepatitis E virus capsid protein E2s domain in complex with Fab C131
Method: EM (single particle) / Resolution: 2.44 Å

61510

9jim

EMDB-61510, PDB-9jim:
Rat hepatitis E virus capsid protein E2s domain in complex with Fab C145
Method: EM (single particle) / Resolution: 2.86 Å

61511

9jin

EMDB-61511, PDB-9jin:
Rat hepatitis E virus capsid protein E2s domain in complex with Fab H4
Method: EM (single particle) / Resolution: 2.56 Å

61512

9jio

EMDB-61512, PDB-9jio:
Hepatitis E virus capsid protein E2s domain (genotype I) in complex with Fab H4
Method: EM (single particle) / Resolution: 2.87 Å

Source
  • rocahepevirus ratti
  • homo sapiens (human)
  • Paslahepevirus balayani
  • hepatitis e virus genotype 1 (isolate human/burma)
  • hepatitis e virus
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / Hepatitis E virus / Capsid protein / E2s domain / Immune complex / C6 antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex / C158 antibody / C127 antibody / C131 antibody / C145 antibody / H4 antibody

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