Multimodal investigation of rat hepatitis E virus antigenicity : Implications for infection, diagnostics, and vaccine efficacy
Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved..
BACKGROUND & AIMS: Rat hepatitis E virus (Orthohepevirus species C; HEV-C1) is an emerging cause of viral hepatitis in humans. HEV-C1 is divergent from other HEV variants infecting humans that belong to Orthohepevirus species A (HEV-A). This study assessed HEV-C1 antigenic divergence from HEV-A and investigated the impact of this divergence on infection susceptibility, serological test sensitivity, and vaccine efficacy.
METHODS: Immunodominant E2s peptide sequences of HEV-A and HEV-C1 were aligned. Interactions of HEV-C1 E2s and anti-HEV-A monoclonal antibodies (mAbs) were modeled. Recombinant peptides incorporating E2s of HEV-A (HEV-A4 p239) and HEV-C1 (HEV-C1 p241) were expressed. HEV-A and HEV-C1 patient sera were tested using antibody enzymatic immunoassays (EIA), antigen EIAs, and HEV-A4 p239/HEV-C1 p241 immunoblots. Rats immunized with HEV-A1 p239 vaccine (Hecolin), HEV-A4 p239 or HEV-C1 p241 peptides were challenged with a HEV-C1 strain.
RESULTS: E2s sequence identity between HEV-A and HEV-C1 was only 48%. There was low conservation at E2s residues (23/53; 43.4%) involved in mAb binding. Anti-HEV-A mAbs bound HEV-C1 poorly in homology modeling and antigen EIAs. Divergence resulted in low sensitivity of commercial antigen (0%) and antibody EIAs (10-70%) for HEV-C1 diagnosis. Species-specific HEV-A4 p239/HEV-C1 p241 immunoblots accurately differentiated HEV-A and HEV-C1 serological profiles in immunized rats (18/18; 100%) and infected-patient sera (32/36; 88.9%). Immunization with Hecolin and HEV-A4 p239 was partially protective while HEV-C1 p241 was fully protective against HEV-C1 infection in rats.
CONCLUSIONS: Antigenic divergence significantly decreases sensitivity of hepatitis E serodiagnostic assays for HEV-C1 infection. Species-specific immunoblots are useful for diagnosing HEV-C1 and for differentiating the serological profiles of HEV-A and HEV-C1. Prior HEV-A exposure is not protective against HEV-C1. HEV-C1 p241 is an immunogenic vaccine candidate against HEV-C1.
LAY SUMMARY: Rat hepatitis E virus (HEV-C1) is a new cause of hepatitis in humans. Using a combination of methods, we showed that HEV-C1 is highly divergent from the usual cause of human hepatitis (HEV-A). This divergence reduces the capacity of existing tests to diagnose HEV-C1 and also indicates that prior exposure to HEV-A (via infection or vaccination) is not protective against HEV-C1.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:74 |
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| Enthalten in: |
Journal of hepatology - 74(2021), 6 vom: 10. Juni, Seite 1315-1324 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sridhar, Siddharth [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.01.2022 Date Revised 28.01.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jhep.2020.12.028 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM324000901 |
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| 041 | |a eng | ||
| 100 | 1 | |a Sridhar, Siddharth |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Multimodal investigation of rat hepatitis E virus antigenicity |b Implications for infection, diagnostics, and vaccine efficacy |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 28.01.2022 | ||
| 500 | |a Date Revised 28.01.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a BACKGROUND & AIMS: Rat hepatitis E virus (Orthohepevirus species C; HEV-C1) is an emerging cause of viral hepatitis in humans. HEV-C1 is divergent from other HEV variants infecting humans that belong to Orthohepevirus species A (HEV-A). This study assessed HEV-C1 antigenic divergence from HEV-A and investigated the impact of this divergence on infection susceptibility, serological test sensitivity, and vaccine efficacy | ||
| 520 | |a METHODS: Immunodominant E2s peptide sequences of HEV-A and HEV-C1 were aligned. Interactions of HEV-C1 E2s and anti-HEV-A monoclonal antibodies (mAbs) were modeled. Recombinant peptides incorporating E2s of HEV-A (HEV-A4 p239) and HEV-C1 (HEV-C1 p241) were expressed. HEV-A and HEV-C1 patient sera were tested using antibody enzymatic immunoassays (EIA), antigen EIAs, and HEV-A4 p239/HEV-C1 p241 immunoblots. Rats immunized with HEV-A1 p239 vaccine (Hecolin), HEV-A4 p239 or HEV-C1 p241 peptides were challenged with a HEV-C1 strain | ||
| 520 | |a RESULTS: E2s sequence identity between HEV-A and HEV-C1 was only 48%. There was low conservation at E2s residues (23/53; 43.4%) involved in mAb binding. Anti-HEV-A mAbs bound HEV-C1 poorly in homology modeling and antigen EIAs. Divergence resulted in low sensitivity of commercial antigen (0%) and antibody EIAs (10-70%) for HEV-C1 diagnosis. Species-specific HEV-A4 p239/HEV-C1 p241 immunoblots accurately differentiated HEV-A and HEV-C1 serological profiles in immunized rats (18/18; 100%) and infected-patient sera (32/36; 88.9%). Immunization with Hecolin and HEV-A4 p239 was partially protective while HEV-C1 p241 was fully protective against HEV-C1 infection in rats | ||
| 520 | |a CONCLUSIONS: Antigenic divergence significantly decreases sensitivity of hepatitis E serodiagnostic assays for HEV-C1 infection. Species-specific immunoblots are useful for diagnosing HEV-C1 and for differentiating the serological profiles of HEV-A and HEV-C1. Prior HEV-A exposure is not protective against HEV-C1. HEV-C1 p241 is an immunogenic vaccine candidate against HEV-C1 | ||
| 520 | |a LAY SUMMARY: Rat hepatitis E virus (HEV-C1) is a new cause of hepatitis in humans. Using a combination of methods, we showed that HEV-C1 is highly divergent from the usual cause of human hepatitis (HEV-A). This divergence reduces the capacity of existing tests to diagnose HEV-C1 and also indicates that prior exposure to HEV-A (via infection or vaccination) is not protective against HEV-C1 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a HEV-C1 | |
| 650 | 4 | |a hepatitis E | |
| 650 | 4 | |a rat hepatitis E | |
| 650 | 4 | |a viral hepatitis | |
| 650 | 4 | |a zoonosis | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
| 650 | 7 | |a Epitopes |2 NLM | |
| 650 | 7 | |a Hepatitis Antibodies |2 NLM | |
| 650 | 7 | |a Hepatitis Antigens |2 NLM | |
| 650 | 7 | |a Vaccines, Synthetic |2 NLM | |
| 650 | 7 | |a Viral Hepatitis Vaccines |2 NLM | |
| 650 | 7 | |a hecolin |2 NLM | |
| 700 | 1 | |a Situ, Jianwen |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Jian-Piao |e verfasserin |4 aut | |
| 700 | 1 | |a Yip, Cyril Chik-Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Shusheng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Anna Jin-Xia |e verfasserin |4 aut | |
| 700 | 1 | |a Wen, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Chew, Nicholas Foo-Siong |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Wan-Mui |e verfasserin |4 aut | |
| 700 | 1 | |a Poon, Rosana Wing-Shan |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Jasper Fuk-Woo |e verfasserin |4 aut | |
| 700 | 1 | |a Tsang, Dominic Ngai-Chong |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Honglin |e verfasserin |4 aut | |
| 700 | 1 | |a Xia, Ning-Shao |e verfasserin |4 aut | |
| 700 | 1 | |a Yuen, Kwok-Yung |e verfasserin |4 aut | |
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