دورية أكاديمية
أعرض في EDS

Inter-epitope spacer variation within polytopic L2-based human papillomavirus antigens affects immunogenicity.

التفاصيل البيبلوغرافية
العنوان: Inter-epitope spacer variation within polytopic L2-based human papillomavirus antigens affects immunogenicity.
المؤلفون: Zhang Y; German Cancer Research Center, Im Neuenheimer Feld 242, 69120, Heidelberg, Germany., Mariz FC; German Cancer Research Center, Im Neuenheimer Feld 242, 69120, Heidelberg, Germany., Sehr P; EMBL-DKFZ Chemical Biology Core Facility, European Molecular Biology Laboratory, 69117, Heidelberg, Germany., Spagnoli G; Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43124, Parma, Italy., Koenig KM; German Cancer Research Center, Im Neuenheimer Feld 242, 69120, Heidelberg, Germany., Çelikyürekli S; German Cancer Research Center, Im Neuenheimer Feld 242, 69120, Heidelberg, Germany., Kreuziger T; Ruprecht-Karls University Heidelberg, Heidelberg, Germany., Zhao X; German Cancer Research Center, Im Neuenheimer Feld 242, 69120, Heidelberg, Germany., Bolchi A; Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43124, Parma, Italy., Ottonello S; Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43124, Parma, Italy., Müller M; German Cancer Research Center, Im Neuenheimer Feld 242, 69120, Heidelberg, Germany. martin.mueller@dkfz-heidelberg.de.
المصدر: NPJ vaccines [NPJ Vaccines] 2024 Feb 24; Vol. 9 (1), pp. 44. Date of Electronic Publication: 2024 Feb 24.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Springer Nature in partnership with the Sealy Center for Vaccine Development Country of Publication: England NLM ID: 101699863 Publication Model: Electronic Cited Medium: Internet ISSN: 2059-0105 (Electronic) Linking ISSN: 20590105 NLM ISO Abbreviation: NPJ Vaccines Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [London] : Springer Nature in partnership with the Sealy Center for Vaccine Development, [2016]-
مستخلص: The human papillomavirus minor capsid protein L2 is being extensively explored in pre-clinical studies as an attractive vaccine antigen capable of inducing broad-spectrum prophylactic antibody responses. Recently, we have developed two HPV vaccine antigens - PANHPVAX and CUT-PANHPVAX- both based on heptameric nanoparticle antigens displaying polytopes of the L2 major cross-neutralizing epitopes of eight mucosal and twelve cutaneous HPV types, respectively. Prompted by the variable neutralizing antibody responses against some of the HPV types targeted by the antigens observed in previous studies, here we investigated the influence on immunogenicity of six distinct glycine-proline spacers inserted upstream to a specific L2 epitope. We show that spacer variants differentially influence antigen immunogenicity in a mouse model, with the antigen constructs M8merV6 and C12merV6 displaying a superior ability in the induction of neutralizing antibodies as determined by pseudovirus-based neutralization assays (PBNAs). L2-peptide enzyme-linked immunosorbent assay (ELISA) assessments determined the total anti-L2 antibody level for each antigen variant, showing for the majority of sera a correlation with their repective neutralizing antibody level. Surface Plasmon Resonance revealed that L2 epitope-specific, neutralizing monoclonal antibodies (mAbs) display distinct avidities to different antigen spacer variants. Furthermore, mAb affinity toward individual spacer variants was well correlated with their neutralizing antibody induction capacity, indicating that the mAb affinity assay predicts L2-based antigen immunogenicity. These observations provide insights on the development and optimization of L2-based HPV vaccines.
(© 2024. The Author(s).)
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معلومات مُعتمدة: 202008080014 CSC | Chinese Government Scholarship
تواريخ الأحداث: Date Created: 20240224 Latest Revision: 20240227
رمز التحديث: 20240227
مُعرف محوري في PubMed: PMC10894200
DOI: 10.1038/s41541-024-00832-0
PMID: 38402256
قاعدة البيانات: MEDLINE
الوصف
تدمد:2059-0105
DOI:10.1038/s41541-024-00832-0