Academic Journal
Effect of Glycan Shift on Antibodies against Hepatitis C Virus E2 412–425 Epitope Elicited by Chimeric sHBsAg-Based Virus-Like Particles
| العنوان: | Effect of Glycan Shift on Antibodies against Hepatitis C Virus E2 412–425 Epitope Elicited by Chimeric sHBsAg-Based Virus-Like Particles |
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| المؤلفون: | Czarnota, Anna, Offersgaard, Anna, Owsianka, Ania, Alzua, Garazi Peña, Bukh, Jens, Gottwein, Judith Margarete, Patel, Arvind H., Bienkowska-Szewczyk, Krystyna, Grzyb, Katarzyna |
| المصدر: | Czarnota , A , Offersgaard , A , Owsianka , A , Alzua , G P , Bukh , J , Gottwein , J M , Patel , A H , Bienkowska-Szewczyk , K & Grzyb , K 2023 , ' Effect of Glycan Shift on Antibodies against Hepatitis C Virus E2 412–425 Epitope Elicited by Chimeric sHBsAg-Based Virus-Like Particles ' , Microbiology Spectrum , vol. 11 , no. 2 , e0024523 . https://doi.org/10.1128/spectrum.02546-22 |
| سنة النشر: | 2023 |
| المجموعة: | University of Copenhagen: Research / Forskning ved Københavns Universitet |
| مصطلحات موضوعية: | glycan shift, hepatitis B virus, hepatitis C virus, vaccines, virus-like particles |
| الوصف: | Two of the most important mechanisms of hepatitis C virus (HCV) immune evasion are the high variability of the amino acid sequence and epitope shielding via heavy glycosylation of the envelope (E) proteins. Previously, we showed that chimeric sHBsAg (hepatitis B virus [HBV] small surface antigen)-based virus-like particles (VLPs) carrying highly conserved epitope I from the HCV E2 glycoprotein (sHBsAg_412–425) elicit broadly neutralizing antibodies (bnAbs). However, many reports have identified escape mutations for such bnAbs that shift the N-glycosylation site from N417 to N415. This shift effectively masks the recognition of epitope I by antibodies raised against the wild-type glycoprotein. To investigate if glycan-shift-mediated immune evasion could be overcome by targeted vaccination strategies, we designed sHBsAg-based VLPs carrying epitope I with an N417S change (sHBsAg_N417S). Studies in BALB/c mice revealed that both sHBsAg_412–425 and sHBsAg_N417S VLPs were immunogenic, eliciting antibodies that recognized peptides encompassing epitope I regardless of the N417S change. However, we observed substantial differences in E1E2 glycoprotein binding and cell culture-derived HCV (HCVcc) neutralization between the sera elicited by sHBsAg_412–425 and those elicited by sHBsAg_N417S VLPs. Our results suggest a complex interplay among antibodies targeting epitope I, the E1E2 glycosylation status, and the epitope or global E1E2 conformation. Additionally, we observed striking similarities in the E1E2 glycoprotein binding patterns and HCVcc neutralization between sHBsAg_412–425 sera and AP33, suggesting that the immunization of mice with sHBsAg_412–425 VLPs can elicit AP33-like antibodies. This study emphasizes the role of antibodies against epitope I and represents an initial effort toward designing an antigen that elicits an immune response against epitope I with a glycan shift change. IMPORTANCE Epitope I, located within amino acids 412 to 423 of the HCV E2 glycoprotein, is an important target for an epitope-based ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| DOI: | 10.1128/spectrum.02546-22 |
| الاتاحة: | https://researchprofiles.ku.dk/da/publications/effect-of-glycan-shift-on-antibodies-against-hepatitis-c-virus-e2-412425-epitope-elicited-by-chimeric-shbsagbased-viruslike-particles(df71f917-2f40-409b-9a76-daa3b2943f30).html https://doi.org/10.1128/spectrum.02546-22 https://curis.ku.dk/ws/files/346256325/spectrum.02546_22.pdf |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.2DF7024A |
| قاعدة البيانات: | BASE |
| DOI: | 10.1128/spectrum.02546-22 |
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