Multimodal investigation of rat hepatitis E virus antigenicity: Implications for infection, diagnostics, and vaccine efficacy
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 im...
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| Veröffentlicht in: | Journal of hepatology 2021-06, Vol.74 (6), p.1315-1324 |
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| creator | Sridhar, Siddharth Situ, Jianwen Cai, Jian-Piao Yip, Cyril Chik-Yan Wu, Shusheng Zhang, Anna Jin-Xia Wen, Lei Chew, Nicholas Foo-Siong Chan, Wan-Mui Poon, Rosana Wing-Shan Chan, Jasper Fuk-Woo Tsang, Dominic Ngai-Chong Chen, Honglin Xia, Ning-Shao Yuen, Kwok-Yung |
| description | 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.
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.
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.
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.
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.
[Display omitted]
•Rat HEV (HEV-C1) is antigenically distinct from human HEV genotypes.•Human HEV-based antigen and antibody assays may not diagnose HEV-C1 i |
| doi_str_mv | 10.1016/j.jhep.2020.12.028 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2512313525</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0168827821000131</els_id><sourcerecordid>2512313525</sourcerecordid><originalsourceid>FETCH-LOGICAL-c450t-d43a5756e147f7b0985254b7bb746a58adc8b5e3283055839aa5b96d2cf69a093</originalsourceid><addsrcrecordid>eNp9kUtP3DAUhS3UCgbaP8CistRNF2TqR5w4VTcVAopE1U27thw_wFFiT-1kpFn0v3OHgS5YdGVd6zvnPg5C55SsKaHN52E9PLjNmhEGH2xNmDxCK9oQUpGmpm_QCiBZSdbKE3RaykAI4aSrj9EJ57IWRMgV-vtjGecwJatHHOLWlTnc6zmkiJPHWc8YOkA9h4Kv8DbkpWAdgXExmDDvvuDbaTMG8yQp2KcMLt6ZfXmBbdD3MYGlKRcgs3irjQnRYec9aMzuHXrr9Vjc--f3DP2-vvp1-b26-3lze_ntrjIw5lzZmmvRisbRuvVtTzopmKj7tu_butFCamtkLxxnkhMhJO-0Fn3XWGZ802nS8TP06eC7yenPAkuqKRTjxlFHl5aimKCMUw6ugH58hQ5pyRGmA0p0La3pE8UOlMmplOy82uQw6bxTlKh9OGpQ-3DUPhxFmYJwQPTh2XrpJ2f_SV7SAODrAXBwi21wWRUTXDTOhgw3VTaF__k_AqaJoRw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2559714125</pqid></control><display><type>article</type><title>Multimodal investigation of rat hepatitis E virus antigenicity: Implications for infection, diagnostics, and vaccine efficacy</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><creator>Sridhar, Siddharth ; Situ, Jianwen ; Cai, Jian-Piao ; Yip, Cyril Chik-Yan ; Wu, Shusheng ; Zhang, Anna Jin-Xia ; Wen, Lei ; Chew, Nicholas Foo-Siong ; Chan, Wan-Mui ; Poon, Rosana Wing-Shan ; Chan, Jasper Fuk-Woo ; Tsang, Dominic Ngai-Chong ; Chen, Honglin ; Xia, Ning-Shao ; Yuen, Kwok-Yung</creator><creatorcontrib>Sridhar, Siddharth ; Situ, Jianwen ; Cai, Jian-Piao ; Yip, Cyril Chik-Yan ; Wu, Shusheng ; Zhang, Anna Jin-Xia ; Wen, Lei ; Chew, Nicholas Foo-Siong ; Chan, Wan-Mui ; Poon, Rosana Wing-Shan ; Chan, Jasper Fuk-Woo ; Tsang, Dominic Ngai-Chong ; Chen, Honglin ; Xia, Ning-Shao ; Yuen, Kwok-Yung</creatorcontrib><description>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.
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.
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.
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.
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.
[Display omitted]
•Rat HEV (HEV-C1) is antigenically distinct from human HEV genotypes.•Human HEV-based antigen and antibody assays may not diagnose HEV-C1 infection.•Prior exposure to human HEV genotypes is not protective against HEV-C1 infection.•An HEV-C1 peptide can be used for specific HEV-C1 serodiagnosis and vaccination.</description><identifier>ISSN: 0168-8278</identifier><identifier>EISSN: 1600-0641</identifier><identifier>DOI: 10.1016/j.jhep.2020.12.028</identifier><identifier>PMID: 33845058</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Animals ; Antibodies, Monoclonal - immunology ; Antibodies, Neutralizing - immunology ; Antigenicity ; Antigens ; Base Sequence ; Child ; Divergence ; Epitopes - immunology ; Female ; Genotype ; Hepatitis ; Hepatitis Antibodies - immunology ; Hepatitis Antigens - immunology ; hepatitis E ; Hepatitis E - blood ; Hepatitis E - prevention & control ; Hepatitis E - veterinary ; Hepatitis E - virology ; Hepatitis E virus - genetics ; Hepatitis E virus - immunology ; HEV-C1 ; Homology ; Humans ; Immunogenicity ; Immunogenicity, Vaccine - immunology ; Infections ; Male ; Middle Aged ; Monoclonal antibodies ; Orthohepevirus ; Peptides ; Phylogeny ; rat hepatitis E ; Rats ; Rats, Sprague-Dawley ; Sensitivity analysis ; Serology ; Species ; Treatment Outcome ; Vaccination ; Vaccination - methods ; Vaccine Efficacy ; Vaccines ; Vaccines, Synthetic - administration & dosage ; viral hepatitis ; Viral Hepatitis Vaccines - administration & dosage ; Viruses ; Young Adult ; zoonosis</subject><ispartof>Journal of hepatology, 2021-06, Vol.74 (6), p.1315-1324</ispartof><rights>2021 European Association for the Study of the Liver</rights><rights>Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.</rights><rights>Copyright Elsevier Science Ltd. Jun 2021</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c450t-d43a5756e147f7b0985254b7bb746a58adc8b5e3283055839aa5b96d2cf69a093</citedby><cites>FETCH-LOGICAL-c450t-d43a5756e147f7b0985254b7bb746a58adc8b5e3283055839aa5b96d2cf69a093</cites><orcidid>0000-0003-4077-3852 ; 0000-0002-6137-8096 ; 0000-0001-8280-2960 ; 0000-0002-9100-1812 ; 0000-0002-9479-1493</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jhep.2020.12.028$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33845058$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sridhar, Siddharth</creatorcontrib><creatorcontrib>Situ, Jianwen</creatorcontrib><creatorcontrib>Cai, Jian-Piao</creatorcontrib><creatorcontrib>Yip, Cyril Chik-Yan</creatorcontrib><creatorcontrib>Wu, Shusheng</creatorcontrib><creatorcontrib>Zhang, Anna Jin-Xia</creatorcontrib><creatorcontrib>Wen, Lei</creatorcontrib><creatorcontrib>Chew, Nicholas Foo-Siong</creatorcontrib><creatorcontrib>Chan, Wan-Mui</creatorcontrib><creatorcontrib>Poon, Rosana Wing-Shan</creatorcontrib><creatorcontrib>Chan, Jasper Fuk-Woo</creatorcontrib><creatorcontrib>Tsang, Dominic Ngai-Chong</creatorcontrib><creatorcontrib>Chen, Honglin</creatorcontrib><creatorcontrib>Xia, Ning-Shao</creatorcontrib><creatorcontrib>Yuen, Kwok-Yung</creatorcontrib><title>Multimodal investigation of rat hepatitis E virus antigenicity: Implications for infection, diagnostics, and vaccine efficacy</title><title>Journal of hepatology</title><addtitle>J Hepatol</addtitle><description>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.
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.
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.
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.
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.
[Display omitted]
•Rat HEV (HEV-C1) is antigenically distinct from human HEV genotypes.•Human HEV-based antigen and antibody assays may not diagnose HEV-C1 infection.•Prior exposure to human HEV genotypes is not protective against HEV-C1 infection.•An HEV-C1 peptide can be used for specific HEV-C1 serodiagnosis and vaccination.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antibodies, Neutralizing - immunology</subject><subject>Antigenicity</subject><subject>Antigens</subject><subject>Base Sequence</subject><subject>Child</subject><subject>Divergence</subject><subject>Epitopes - immunology</subject><subject>Female</subject><subject>Genotype</subject><subject>Hepatitis</subject><subject>Hepatitis Antibodies - immunology</subject><subject>Hepatitis Antigens - immunology</subject><subject>hepatitis E</subject><subject>Hepatitis E - blood</subject><subject>Hepatitis E - prevention & control</subject><subject>Hepatitis E - veterinary</subject><subject>Hepatitis E - virology</subject><subject>Hepatitis E virus - genetics</subject><subject>Hepatitis E virus - immunology</subject><subject>HEV-C1</subject><subject>Homology</subject><subject>Humans</subject><subject>Immunogenicity</subject><subject>Immunogenicity, Vaccine - immunology</subject><subject>Infections</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Monoclonal antibodies</subject><subject>Orthohepevirus</subject><subject>Peptides</subject><subject>Phylogeny</subject><subject>rat hepatitis E</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Sensitivity analysis</subject><subject>Serology</subject><subject>Species</subject><subject>Treatment Outcome</subject><subject>Vaccination</subject><subject>Vaccination - methods</subject><subject>Vaccine Efficacy</subject><subject>Vaccines</subject><subject>Vaccines, Synthetic - administration & dosage</subject><subject>viral hepatitis</subject><subject>Viral Hepatitis Vaccines - administration & dosage</subject><subject>Viruses</subject><subject>Young Adult</subject><subject>zoonosis</subject><issn>0168-8278</issn><issn>1600-0641</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUtP3DAUhS3UCgbaP8CistRNF2TqR5w4VTcVAopE1U27thw_wFFiT-1kpFn0v3OHgS5YdGVd6zvnPg5C55SsKaHN52E9PLjNmhEGH2xNmDxCK9oQUpGmpm_QCiBZSdbKE3RaykAI4aSrj9EJ57IWRMgV-vtjGecwJatHHOLWlTnc6zmkiJPHWc8YOkA9h4Kv8DbkpWAdgXExmDDvvuDbaTMG8yQp2KcMLt6ZfXmBbdD3MYGlKRcgs3irjQnRYec9aMzuHXrr9Vjc--f3DP2-vvp1-b26-3lze_ntrjIw5lzZmmvRisbRuvVtTzopmKj7tu_butFCamtkLxxnkhMhJO-0Fn3XWGZ802nS8TP06eC7yenPAkuqKRTjxlFHl5aimKCMUw6ugH58hQ5pyRGmA0p0La3pE8UOlMmplOy82uQw6bxTlKh9OGpQ-3DUPhxFmYJwQPTh2XrpJ2f_SV7SAODrAXBwi21wWRUTXDTOhgw3VTaF__k_AqaJoRw</recordid><startdate>202106</startdate><enddate>202106</enddate><creator>Sridhar, Siddharth</creator><creator>Situ, Jianwen</creator><creator>Cai, Jian-Piao</creator><creator>Yip, Cyril Chik-Yan</creator><creator>Wu, Shusheng</creator><creator>Zhang, Anna Jin-Xia</creator><creator>Wen, Lei</creator><creator>Chew, Nicholas Foo-Siong</creator><creator>Chan, Wan-Mui</creator><creator>Poon, Rosana Wing-Shan</creator><creator>Chan, Jasper Fuk-Woo</creator><creator>Tsang, Dominic Ngai-Chong</creator><creator>Chen, Honglin</creator><creator>Xia, Ning-Shao</creator><creator>Yuen, Kwok-Yung</creator><general>Elsevier B.V</general><general>Elsevier Science Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4077-3852</orcidid><orcidid>https://orcid.org/0000-0002-6137-8096</orcidid><orcidid>https://orcid.org/0000-0001-8280-2960</orcidid><orcidid>https://orcid.org/0000-0002-9100-1812</orcidid><orcidid>https://orcid.org/0000-0002-9479-1493</orcidid></search><sort><creationdate>202106</creationdate><title>Multimodal investigation of rat hepatitis E virus antigenicity: Implications for infection, diagnostics, and vaccine efficacy</title><author>Sridhar, Siddharth ; Situ, Jianwen ; Cai, Jian-Piao ; Yip, Cyril Chik-Yan ; Wu, Shusheng ; Zhang, Anna Jin-Xia ; Wen, Lei ; Chew, Nicholas Foo-Siong ; Chan, Wan-Mui ; Poon, Rosana Wing-Shan ; Chan, Jasper Fuk-Woo ; Tsang, Dominic Ngai-Chong ; Chen, Honglin ; Xia, Ning-Shao ; Yuen, Kwok-Yung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c450t-d43a5756e147f7b0985254b7bb746a58adc8b5e3283055839aa5b96d2cf69a093</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Animals</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Antibodies, Neutralizing - immunology</topic><topic>Antigenicity</topic><topic>Antigens</topic><topic>Base Sequence</topic><topic>Child</topic><topic>Divergence</topic><topic>Epitopes - immunology</topic><topic>Female</topic><topic>Genotype</topic><topic>Hepatitis</topic><topic>Hepatitis Antibodies - immunology</topic><topic>Hepatitis Antigens - immunology</topic><topic>hepatitis E</topic><topic>Hepatitis E - blood</topic><topic>Hepatitis E - prevention & control</topic><topic>Hepatitis E - veterinary</topic><topic>Hepatitis E - virology</topic><topic>Hepatitis E virus - genetics</topic><topic>Hepatitis E virus - immunology</topic><topic>HEV-C1</topic><topic>Homology</topic><topic>Humans</topic><topic>Immunogenicity</topic><topic>Immunogenicity, Vaccine - immunology</topic><topic>Infections</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Monoclonal antibodies</topic><topic>Orthohepevirus</topic><topic>Peptides</topic><topic>Phylogeny</topic><topic>rat hepatitis E</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Sensitivity analysis</topic><topic>Serology</topic><topic>Species</topic><topic>Treatment Outcome</topic><topic>Vaccination</topic><topic>Vaccination - methods</topic><topic>Vaccine Efficacy</topic><topic>Vaccines</topic><topic>Vaccines, Synthetic - administration & dosage</topic><topic>viral hepatitis</topic><topic>Viral Hepatitis Vaccines - administration & dosage</topic><topic>Viruses</topic><topic>Young Adult</topic><topic>zoonosis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sridhar, Siddharth</creatorcontrib><creatorcontrib>Situ, Jianwen</creatorcontrib><creatorcontrib>Cai, Jian-Piao</creatorcontrib><creatorcontrib>Yip, Cyril Chik-Yan</creatorcontrib><creatorcontrib>Wu, Shusheng</creatorcontrib><creatorcontrib>Zhang, Anna Jin-Xia</creatorcontrib><creatorcontrib>Wen, Lei</creatorcontrib><creatorcontrib>Chew, Nicholas Foo-Siong</creatorcontrib><creatorcontrib>Chan, Wan-Mui</creatorcontrib><creatorcontrib>Poon, Rosana Wing-Shan</creatorcontrib><creatorcontrib>Chan, Jasper Fuk-Woo</creatorcontrib><creatorcontrib>Tsang, Dominic Ngai-Chong</creatorcontrib><creatorcontrib>Chen, Honglin</creatorcontrib><creatorcontrib>Xia, Ning-Shao</creatorcontrib><creatorcontrib>Yuen, Kwok-Yung</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of hepatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sridhar, Siddharth</au><au>Situ, Jianwen</au><au>Cai, Jian-Piao</au><au>Yip, Cyril Chik-Yan</au><au>Wu, Shusheng</au><au>Zhang, Anna Jin-Xia</au><au>Wen, Lei</au><au>Chew, Nicholas Foo-Siong</au><au>Chan, Wan-Mui</au><au>Poon, Rosana Wing-Shan</au><au>Chan, Jasper Fuk-Woo</au><au>Tsang, Dominic Ngai-Chong</au><au>Chen, Honglin</au><au>Xia, Ning-Shao</au><au>Yuen, Kwok-Yung</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Multimodal investigation of rat hepatitis E virus antigenicity: Implications for infection, diagnostics, and vaccine efficacy</atitle><jtitle>Journal of hepatology</jtitle><addtitle>J Hepatol</addtitle><date>2021-06</date><risdate>2021</risdate><volume>74</volume><issue>6</issue><spage>1315</spage><epage>1324</epage><pages>1315-1324</pages><issn>0168-8278</issn><eissn>1600-0641</eissn><abstract>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.
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.
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.
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.
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.
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•Rat HEV (HEV-C1) is antigenically distinct from human HEV genotypes.•Human HEV-based antigen and antibody assays may not diagnose HEV-C1 infection.•Prior exposure to human HEV genotypes is not protective against HEV-C1 infection.•An HEV-C1 peptide can be used for specific HEV-C1 serodiagnosis and vaccination.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>33845058</pmid><doi>10.1016/j.jhep.2020.12.028</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-4077-3852</orcidid><orcidid>https://orcid.org/0000-0002-6137-8096</orcidid><orcidid>https://orcid.org/0000-0001-8280-2960</orcidid><orcidid>https://orcid.org/0000-0002-9100-1812</orcidid><orcidid>https://orcid.org/0000-0002-9479-1493</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0168-8278 |
| ispartof | Journal of hepatology, 2021-06, Vol.74 (6), p.1315-1324 |
| issn | 0168-8278 1600-0641 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2512313525 |
| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Adolescent Adult Aged Aged, 80 and over Animals Antibodies, Monoclonal - immunology Antibodies, Neutralizing - immunology Antigenicity Antigens Base Sequence Child Divergence Epitopes - immunology Female Genotype Hepatitis Hepatitis Antibodies - immunology Hepatitis Antigens - immunology hepatitis E Hepatitis E - blood Hepatitis E - prevention & control Hepatitis E - veterinary Hepatitis E - virology Hepatitis E virus - genetics Hepatitis E virus - immunology HEV-C1 Homology Humans Immunogenicity Immunogenicity, Vaccine - immunology Infections Male Middle Aged Monoclonal antibodies Orthohepevirus Peptides Phylogeny rat hepatitis E Rats Rats, Sprague-Dawley Sensitivity analysis Serology Species Treatment Outcome Vaccination Vaccination - methods Vaccine Efficacy Vaccines Vaccines, Synthetic - administration & dosage viral hepatitis Viral Hepatitis Vaccines - administration & dosage Viruses Young Adult zoonosis |
| title | Multimodal investigation of rat hepatitis E virus antigenicity: Implications for infection, diagnostics, and vaccine efficacy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-28T07%3A19%3A39IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Multimodal%20investigation%20of%20rat%20hepatitis%20E%20virus%20antigenicity:%20Implications%20for%20infection,%20diagnostics,%20and%20vaccine%20efficacy&rft.jtitle=Journal%20of%20hepatology&rft.au=Sridhar,%20Siddharth&rft.date=2021-06&rft.volume=74&rft.issue=6&rft.spage=1315&rft.epage=1324&rft.pages=1315-1324&rft.issn=0168-8278&rft.eissn=1600-0641&rft_id=info:doi/10.1016/j.jhep.2020.12.028&rft_dat=%3Cproquest_cross%3E2512313525%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2559714125&rft_id=info:pmid/33845058&rft_els_id=S0168827821000131&rfr_iscdi=true |