Unexpected rise in the circulation of complex HBV variants enriched of HBsAg vaccine-escape mutations in HBV genotype-D: potential impact on HBsAg detection/quantification and vaccination strategies
Specific HBsAg mutations are known to hamper HBsAg recognition by neutralizing antibodies thus challenging HBV-vaccination efficacy. Nevertheless, information on their impact and spreading over time is limited. Here, we characterize the circulation of vaccine-escape mutations from 2005 to 2019 and t...
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| creator | Piermatteo, Lorenzo D'Anna, Stefano Bertoli, Ada Bellocchi, Maria Carioti, Luca Fabeni, Lavinia Alkhatib, Mohammad Frazia, Simone La Lichtner, Miriam Mastroianni, Claudio Sanctis, Giuseppe De Marignani, Massimo Pasquazzi, Caterina Iapadre, Nerio Parruti, Giustino Cappiello, Giuseppina Vecchiet, Jacopo Malagnino, Vincenzo Grelli, Sandro Ceccherini-Silbertein, Francesca Andreoni, Massimo Sarmati, Loredana Svicher, Valentina Salpini, Romina |
| description | Specific HBsAg mutations are known to hamper HBsAg recognition by neutralizing antibodies thus challenging HBV-vaccination efficacy. Nevertheless, information on their impact and spreading over time is limited. Here, we characterize the circulation of vaccine-escape mutations from 2005 to 2019 and their correlation with virological parameters in a large cohort of patients infected with HBV genotype-D (N = 947), dominant in Europe. Overall, 17.7% of patients harbours ≥1 vaccine-escape mutation with the highest prevalence in subgenotype-D3. Notably, complex profiles (characterized by ≥2 vaccine-escape mutations) are revealed in 3.1% of patients with a prevalence rising from 0.4% in 2005-2009 to 3.0% in 2010-2014 and 5.1% in 2015-2019 (P = 0.007) (OR[95%CI]:11.04[1.42-85.58], P = 0.02, by multivariable-analysis). The presence of complex profiles correlates with lower HBsAg-levels (median[IQR]:40[0-2905]IU/mL for complex profiles vs 2078[115-6037]IU/ml and 1881[410-7622]IU/mL for single or no vaccine-escape mutation [P |
| doi_str_mv | 10.1080/22221751.2023.2219347 |
| format | Article |
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Nevertheless, information on their impact and spreading over time is limited. Here, we characterize the circulation of vaccine-escape mutations from 2005 to 2019 and their correlation with virological parameters in a large cohort of patients infected with HBV genotype-D (N = 947), dominant in Europe. Overall, 17.7% of patients harbours ≥1 vaccine-escape mutation with the highest prevalence in subgenotype-D3. Notably, complex profiles (characterized by ≥2 vaccine-escape mutations) are revealed in 3.1% of patients with a prevalence rising from 0.4% in 2005-2009 to 3.0% in 2010-2014 and 5.1% in 2015-2019 (P = 0.007) (OR[95%CI]:11.04[1.42-85.58], P = 0.02, by multivariable-analysis). The presence of complex profiles correlates with lower HBsAg-levels (median[IQR]:40[0-2905]IU/mL for complex profiles vs 2078[115-6037]IU/ml and 1881[410-7622]IU/mL for single or no vaccine-escape mutation [P < 0.02]). Even more, the presence of complex profiles correlates with HBsAg-negativity despite HBV-DNA positivity (HBsAg-negativity in 34.8% with ≥2 vaccine-escape mutations vs 6.7% and 2.3% with a single or no vaccine-escape mutation, P < 0.007). These in-vivo findings are in keeping with our in-vitro results showing the ability of these mutations in hampering HBsAg secretion or HBsAg recognition by diagnostic antibodies. In conclusion, vaccine-escape mutations, single or in complex profiles, circulate in a not negligible fraction of HBV genotype-D infected patients with an increasing temporal trend, suggesting a progressive enrichment in the circulation of variants able to evade humoral responses. This should be considered for a proper clinical interpretation of HBsAg-results and for the development of novel vaccine formulations for prophylactic and therapeutic purposes.</description><identifier>ISSN: 2222-1751</identifier><identifier>EISSN: 2222-1751</identifier><identifier>DOI: 10.1080/22221751.2023.2219347</identifier><identifier>PMID: 37288750</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>DNA, Viral - genetics ; Genotype ; Genotype & phenotype ; HBsAg ; HBsAg antigenicity ; HBsAg secretion ; HBV ; Hepatitis ; Hepatitis B Surface Antigens - genetics ; Hepatitis B Vaccines ; Hepatitis B virus ; Humans ; Immunization ; Mutation ; Vaccination ; vaccine-escape mutations ; Vaccines</subject><ispartof>Emerging microbes & infections, 2023-12, Vol.12 (1), p.2219347-2219347</ispartof><rights>2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd 2023</rights><rights>2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd. This work is licensed under the Creative Commons Attribution – Non-Commercial License http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd 2023 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c563t-92d5ba133609b903657e826c644575b6da87faeb26573aa5ee67920ddf08f5d63</citedby><cites>FETCH-LOGICAL-c563t-92d5ba133609b903657e826c644575b6da87faeb26573aa5ee67920ddf08f5d63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10251786/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10251786/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,27479,27901,27902,53766,53768,59116,59117</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37288750$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Piermatteo, Lorenzo</creatorcontrib><creatorcontrib>D'Anna, Stefano</creatorcontrib><creatorcontrib>Bertoli, Ada</creatorcontrib><creatorcontrib>Bellocchi, Maria</creatorcontrib><creatorcontrib>Carioti, Luca</creatorcontrib><creatorcontrib>Fabeni, Lavinia</creatorcontrib><creatorcontrib>Alkhatib, Mohammad</creatorcontrib><creatorcontrib>Frazia, Simone La</creatorcontrib><creatorcontrib>Lichtner, Miriam</creatorcontrib><creatorcontrib>Mastroianni, Claudio</creatorcontrib><creatorcontrib>Sanctis, Giuseppe De</creatorcontrib><creatorcontrib>Marignani, Massimo</creatorcontrib><creatorcontrib>Pasquazzi, Caterina</creatorcontrib><creatorcontrib>Iapadre, Nerio</creatorcontrib><creatorcontrib>Parruti, Giustino</creatorcontrib><creatorcontrib>Cappiello, Giuseppina</creatorcontrib><creatorcontrib>Vecchiet, Jacopo</creatorcontrib><creatorcontrib>Malagnino, Vincenzo</creatorcontrib><creatorcontrib>Grelli, Sandro</creatorcontrib><creatorcontrib>Ceccherini-Silbertein, Francesca</creatorcontrib><creatorcontrib>Andreoni, Massimo</creatorcontrib><creatorcontrib>Sarmati, Loredana</creatorcontrib><creatorcontrib>Svicher, Valentina</creatorcontrib><creatorcontrib>Salpini, Romina</creatorcontrib><title>Unexpected rise in the circulation of complex HBV variants enriched of HBsAg vaccine-escape mutations in HBV genotype-D: potential impact on HBsAg detection/quantification and vaccination strategies</title><title>Emerging microbes & infections</title><addtitle>Emerg Microbes Infect</addtitle><description>Specific HBsAg mutations are known to hamper HBsAg recognition by neutralizing antibodies thus challenging HBV-vaccination efficacy. Nevertheless, information on their impact and spreading over time is limited. Here, we characterize the circulation of vaccine-escape mutations from 2005 to 2019 and their correlation with virological parameters in a large cohort of patients infected with HBV genotype-D (N = 947), dominant in Europe. Overall, 17.7% of patients harbours ≥1 vaccine-escape mutation with the highest prevalence in subgenotype-D3. Notably, complex profiles (characterized by ≥2 vaccine-escape mutations) are revealed in 3.1% of patients with a prevalence rising from 0.4% in 2005-2009 to 3.0% in 2010-2014 and 5.1% in 2015-2019 (P = 0.007) (OR[95%CI]:11.04[1.42-85.58], P = 0.02, by multivariable-analysis). The presence of complex profiles correlates with lower HBsAg-levels (median[IQR]:40[0-2905]IU/mL for complex profiles vs 2078[115-6037]IU/ml and 1881[410-7622]IU/mL for single or no vaccine-escape mutation [P < 0.02]). Even more, the presence of complex profiles correlates with HBsAg-negativity despite HBV-DNA positivity (HBsAg-negativity in 34.8% with ≥2 vaccine-escape mutations vs 6.7% and 2.3% with a single or no vaccine-escape mutation, P < 0.007). These in-vivo findings are in keeping with our in-vitro results showing the ability of these mutations in hampering HBsAg secretion or HBsAg recognition by diagnostic antibodies. In conclusion, vaccine-escape mutations, single or in complex profiles, circulate in a not negligible fraction of HBV genotype-D infected patients with an increasing temporal trend, suggesting a progressive enrichment in the circulation of variants able to evade humoral responses. This should be considered for a proper clinical interpretation of HBsAg-results and for the development of novel vaccine formulations for prophylactic and therapeutic purposes.</description><subject>DNA, Viral - genetics</subject><subject>Genotype</subject><subject>Genotype & phenotype</subject><subject>HBsAg</subject><subject>HBsAg antigenicity</subject><subject>HBsAg secretion</subject><subject>HBV</subject><subject>Hepatitis</subject><subject>Hepatitis B Surface Antigens - genetics</subject><subject>Hepatitis B Vaccines</subject><subject>Hepatitis B virus</subject><subject>Humans</subject><subject>Immunization</subject><subject>Mutation</subject><subject>Vaccination</subject><subject>vaccine-escape mutations</subject><subject>Vaccines</subject><issn>2222-1751</issn><issn>2222-1751</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>0YH</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNp9Uk1P3DAQjapWBVF-QitLvfSy4Nhx7PTSAv0ACamX0qs160x2jRI72A5l_2B_Vx12QdBD5-LxzHtvxtYrirclPSqposcsRylFecQo40c5b3glXxT7c30xN14-yfeKwxivaQ5J66qsXhd7XDKlpKD7xZ8rh3cjmoQtCTYisY6kNRJjg5l6SNY74jti_DD2eEfOT3-RWwgWXIoEXbBmnYkZcH4aT1a5ZYx1uMBoYEQyTOleIc6qM3WFzqfNiIsvH8noE7pkoSd2GMEk4t1OpcWUF8q845spD7KdNdtFwLW7Edt7TAESrizGN8WrDvqIh7vzoLj69vXn2fni8sf3i7OTy4URNU-LhrViCSXnNW2WDeW1kKhYbeqqElIs6xaU7ACXLDc4gECsZcNo23ZUdaKt-UFxsdVtPVzrMdgBwkZ7sPq-4MNKQ0jW9KjLZcVNx5ii0FbMcJCy6ZqqlVwhSNFkrU9brXFaDtia_BsB-meizzvOrvXK3-qSMlFKNW_zYacQ_M2EMenBRoN9Dw79FDVTjDdKifth7_-BXvspuPxXGVXLSpWV4hkltigTfIwBu8dtSqpn5-kH5-nZeXrnvMx79_Qpj6wHn2XA5y3Aus6HAX770Lc6wab3oQvgjI2a_3_GX9XA6uU</recordid><startdate>202312</startdate><enddate>202312</enddate><creator>Piermatteo, Lorenzo</creator><creator>D'Anna, Stefano</creator><creator>Bertoli, Ada</creator><creator>Bellocchi, Maria</creator><creator>Carioti, Luca</creator><creator>Fabeni, Lavinia</creator><creator>Alkhatib, Mohammad</creator><creator>Frazia, Simone La</creator><creator>Lichtner, Miriam</creator><creator>Mastroianni, Claudio</creator><creator>Sanctis, Giuseppe De</creator><creator>Marignani, Massimo</creator><creator>Pasquazzi, Caterina</creator><creator>Iapadre, Nerio</creator><creator>Parruti, Giustino</creator><creator>Cappiello, Giuseppina</creator><creator>Vecchiet, Jacopo</creator><creator>Malagnino, Vincenzo</creator><creator>Grelli, Sandro</creator><creator>Ceccherini-Silbertein, Francesca</creator><creator>Andreoni, Massimo</creator><creator>Sarmati, Loredana</creator><creator>Svicher, Valentina</creator><creator>Salpini, Romina</creator><general>Taylor & Francis</general><general>Taylor & Francis Ltd</general><general>Taylor & Francis Group</general><scope>0YH</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>202312</creationdate><title>Unexpected rise in the circulation of complex HBV variants enriched of HBsAg vaccine-escape mutations in HBV genotype-D: potential impact on HBsAg detection/quantification and vaccination strategies</title><author>Piermatteo, Lorenzo ; D'Anna, Stefano ; Bertoli, Ada ; Bellocchi, Maria ; Carioti, Luca ; Fabeni, Lavinia ; Alkhatib, Mohammad ; Frazia, Simone La ; Lichtner, Miriam ; Mastroianni, Claudio ; Sanctis, Giuseppe De ; Marignani, Massimo ; Pasquazzi, Caterina ; Iapadre, Nerio ; Parruti, Giustino ; Cappiello, Giuseppina ; Vecchiet, Jacopo ; Malagnino, Vincenzo ; Grelli, Sandro ; Ceccherini-Silbertein, Francesca ; Andreoni, Massimo ; Sarmati, Loredana ; Svicher, Valentina ; Salpini, Romina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c563t-92d5ba133609b903657e826c644575b6da87faeb26573aa5ee67920ddf08f5d63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>DNA, Viral - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Emerging microbes & infections</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Piermatteo, Lorenzo</au><au>D'Anna, Stefano</au><au>Bertoli, Ada</au><au>Bellocchi, Maria</au><au>Carioti, Luca</au><au>Fabeni, Lavinia</au><au>Alkhatib, Mohammad</au><au>Frazia, Simone La</au><au>Lichtner, Miriam</au><au>Mastroianni, Claudio</au><au>Sanctis, Giuseppe De</au><au>Marignani, Massimo</au><au>Pasquazzi, Caterina</au><au>Iapadre, Nerio</au><au>Parruti, Giustino</au><au>Cappiello, Giuseppina</au><au>Vecchiet, Jacopo</au><au>Malagnino, Vincenzo</au><au>Grelli, Sandro</au><au>Ceccherini-Silbertein, Francesca</au><au>Andreoni, Massimo</au><au>Sarmati, Loredana</au><au>Svicher, Valentina</au><au>Salpini, Romina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Unexpected rise in the circulation of complex HBV variants enriched of HBsAg vaccine-escape mutations in HBV genotype-D: potential impact on HBsAg detection/quantification and vaccination strategies</atitle><jtitle>Emerging microbes & infections</jtitle><addtitle>Emerg Microbes Infect</addtitle><date>2023-12</date><risdate>2023</risdate><volume>12</volume><issue>1</issue><spage>2219347</spage><epage>2219347</epage><pages>2219347-2219347</pages><issn>2222-1751</issn><eissn>2222-1751</eissn><abstract>Specific HBsAg mutations are known to hamper HBsAg recognition by neutralizing antibodies thus challenging HBV-vaccination efficacy. Nevertheless, information on their impact and spreading over time is limited. Here, we characterize the circulation of vaccine-escape mutations from 2005 to 2019 and their correlation with virological parameters in a large cohort of patients infected with HBV genotype-D (N = 947), dominant in Europe. Overall, 17.7% of patients harbours ≥1 vaccine-escape mutation with the highest prevalence in subgenotype-D3. Notably, complex profiles (characterized by ≥2 vaccine-escape mutations) are revealed in 3.1% of patients with a prevalence rising from 0.4% in 2005-2009 to 3.0% in 2010-2014 and 5.1% in 2015-2019 (P = 0.007) (OR[95%CI]:11.04[1.42-85.58], P = 0.02, by multivariable-analysis). The presence of complex profiles correlates with lower HBsAg-levels (median[IQR]:40[0-2905]IU/mL for complex profiles vs 2078[115-6037]IU/ml and 1881[410-7622]IU/mL for single or no vaccine-escape mutation [P < 0.02]). Even more, the presence of complex profiles correlates with HBsAg-negativity despite HBV-DNA positivity (HBsAg-negativity in 34.8% with ≥2 vaccine-escape mutations vs 6.7% and 2.3% with a single or no vaccine-escape mutation, P < 0.007). These in-vivo findings are in keeping with our in-vitro results showing the ability of these mutations in hampering HBsAg secretion or HBsAg recognition by diagnostic antibodies. In conclusion, vaccine-escape mutations, single or in complex profiles, circulate in a not negligible fraction of HBV genotype-D infected patients with an increasing temporal trend, suggesting a progressive enrichment in the circulation of variants able to evade humoral responses. This should be considered for a proper clinical interpretation of HBsAg-results and for the development of novel vaccine formulations for prophylactic and therapeutic purposes.</abstract><cop>United States</cop><pub>Taylor & Francis</pub><pmid>37288750</pmid><doi>10.1080/22221751.2023.2219347</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Emerging microbes & infections, 2023-12, Vol.12 (1), p.2219347-2219347 |
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| source | Taylor & Francis Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | DNA, Viral - genetics Genotype Genotype & phenotype HBsAg HBsAg antigenicity HBsAg secretion HBV Hepatitis Hepatitis B Surface Antigens - genetics Hepatitis B Vaccines Hepatitis B virus Humans Immunization Mutation Vaccination vaccine-escape mutations Vaccines |
| title | Unexpected rise in the circulation of complex HBV variants enriched of HBsAg vaccine-escape mutations in HBV genotype-D: potential impact on HBsAg detection/quantification and vaccination strategies |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-19T23%3A21%3A15IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Unexpected%20rise%20in%20the%20circulation%20of%20complex%20HBV%20variants%20enriched%20of%20HBsAg%20vaccine-escape%20mutations%20in%20HBV%20genotype-D:%20potential%20impact%20on%20HBsAg%20detection/quantification%20and%20vaccination%20strategies&rft.jtitle=Emerging%20microbes%20&%20infections&rft.au=Piermatteo,%20Lorenzo&rft.date=2023-12&rft.volume=12&rft.issue=1&rft.spage=2219347&rft.epage=2219347&rft.pages=2219347-2219347&rft.issn=2222-1751&rft.eissn=2222-1751&rft_id=info:doi/10.1080/22221751.2023.2219347&rft_dat=%3Cproquest_pubme%3E2823988559%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2867481483&rft_id=info:pmid/37288750&rft_doaj_id=oai_doaj_org_article_1b43cf2280ad42c3a779f94d738ea759&rfr_iscdi=true |