Enhanced Antibody Response to the Conformational Non-RBD Region DNA Prime-protein Boost Elicits Broad Cross-neutralization Against SARS-CoV-2 Variants

Overview

Journal Emerg Microbes Infect

Specialty Infectious Diseases

Date 2024 Dec 27

PMID 39727342

Authors

Yun-Fei Ma

Kun Chen

Bowen Xie

Jiayi Zhu

Xuan He

Chunying Chen

Yuhe Renee Yang

Ye Liu

Affiliations

Soon will be listed here.

Abstract

Preventing immune escape of SARS-CoV-2 variants is crucial in vaccine development to ensure broad protection against the virus. Conformational epitopes beyond the RBD region are vital components of the spike protein but have received limited attention in the development of broadly protective SARS-CoV-2 vaccines. In this study, we used a DNA prime-protein boost regimen to evaluate the broad cross-neutralization potential of immune response targeting conformational non-RBD region against SARS-CoV-2 viruses in mice. Mice with enhanced antibody responses targeting conformational non-RBD region show better performance in cross-neutralization against the Wuhan-01, Delta, and Omicron subvariants. analyzing the distribution of conformational epitopes, and quantifying epitope-specific binding antibodies, we verified a positive correlation between the proportion of binding antibodies against the N-terminal domain (NTD) supersite (a conformational non-RBD epitope) and SARS-CoV-2 neutralization potency. The current work highlights the importance of high ratio of conformational non-RBD-specific binding antibodies in mediating viral cross-neutralization and provides new insight into overcoming the immune escape of SARS-CoV-2 variants.

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