Epitope-focused Vaccine Immunogens Design Using Tailored Horseshoe-shaped Scaffold

Overview

Journal J Nanobiotechnology

Publisher Biomed Central

Specialty Biotechnology

Date 2025 Feb 19

PMID 39966941

Authors

Fangxin Zhao

Yue Zhang

Zhiling Zhang

Zhengshan Chen

Xiaolin Wang

Shaoyan Wang

Ruihua Li

Yaohui Li

Zhang Zhang

Wanru Zheng

Yudong Wang

Zhe Zhang

Shipo Wu

Yilong Yang

Jun Zhang

Xiaodong Zai

Junjie Xu

Wei Chen

Affiliations

Soon will be listed here.

Abstract

The continuous emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants highlights the need to update coronavirus 2019 disease (COVID-19) vaccine components. Epitope-based vaccine designs targeting conserved and immunorecessive regions of SARS-CoV-2 are critically needed. Here, we report an engineered epitope-focused immunogen design based on a novel horseshoe-shaped natural protein scaffold, named ribonuclease inhibitor 1 (RNH1), that can multiply display of conserved neutralizing epitopes from SARS-CoV-2 S2 stem helix. The designed immunogen RNH1-S1139 demonstrates high binding affinity to S2-specific neutralizing antibodies and elicits robust epitope-targeted antibody responses either through homologous or heterologous vaccination regimens. RNH1-S1139 immune serum has been proven to have similar binding ability against SARS-CoV, SARS-CoV-2 and its variants, providing broad-spectrum protection as a membrane fusion inhibitor. Further studies showed that RNH1 has the potential to serve as a versatile scaffold that displays other helical epitopes from various antigens, including respiratory syncytial virus (RSV) F glycoprotein. Our proposed immunogen engineering strategy via tailored horseshoe-shape nano-scaffold supports the continued development of epitope-focused vaccines as part of a next-generation vaccine design.

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