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 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Emerging microbes & infections - 12(2023), 1 vom: 08. Dez., Seite 2219347 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Piermatteo, Lorenzo [VerfasserIn] |
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| Links: |
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| Themen: |
DNA, Viral |
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| Anmerkungen: |
Date Completed 09.06.2023 Date Revised 12.06.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1080/22221751.2023.2219347 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM357906039 |
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| 245 | 1 | 0 | |a Unexpected rise in the circulation of complex HBV variants enriched of HBsAg vaccine-escape mutations in HBV genotype-D |b potential impact on HBsAg detection/quantification and vaccination strategies |
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| 500 | |a Date Completed 09.06.2023 | ||
| 500 | |a Date Revised 12.06.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a HBV | |
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| 650 | 4 | |a HBsAg secretion | |
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| 700 | 1 | |a Bertoli, Ada |e verfasserin |4 aut | |
| 700 | 1 | |a Bellocchi, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Carioti, Luca |e verfasserin |4 aut | |
| 700 | 1 | |a Fabeni, Lavinia |e verfasserin |4 aut | |
| 700 | 1 | |a Alkhatib, Mohammad |e verfasserin |4 aut | |
| 700 | 1 | |a Frazia, Simone La |e verfasserin |4 aut | |
| 700 | 1 | |a Lichtner, Miriam |e verfasserin |4 aut | |
| 700 | 1 | |a Mastroianni, Claudio |e verfasserin |4 aut | |
| 700 | 1 | |a Sanctis, Giuseppe De |e verfasserin |4 aut | |
| 700 | 1 | |a Marignani, Massimo |e verfasserin |4 aut | |
| 700 | 1 | |a Pasquazzi, Caterina |e verfasserin |4 aut | |
| 700 | 1 | |a Iapadre, Nerio |e verfasserin |4 aut | |
| 700 | 1 | |a Parruti, Giustino |e verfasserin |4 aut | |
| 700 | 1 | |a Cappiello, Giuseppina |e verfasserin |4 aut | |
| 700 | 1 | |a Vecchiet, Jacopo |e verfasserin |4 aut | |
| 700 | 1 | |a Malagnino, Vincenzo |e verfasserin |4 aut | |
| 700 | 1 | |a Grelli, Sandro |e verfasserin |4 aut | |
| 700 | 1 | |a Ceccherini-Silbertein, Francesca |e verfasserin |4 aut | |
| 700 | 1 | |a Andreoni, Massimo |e verfasserin |4 aut | |
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| 700 | 1 | |a Svicher, Valentina |e verfasserin |4 aut | |
| 700 | 1 | |a Salpini, Romina |e verfasserin |4 aut | |
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