Enhanced antibody response to the conformational non-RBD region via DNA prime-protein boost elicits broad cross-neutralization against SARS-CoV-2 variants
Year: 2024
Type: article
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. Via 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.
Source: Emerging Microbes & Infections
Institutions: Chinese Academy of Medical Sciences & Peking Union Medical College, Chinese Academy of Sciences, National Center for Nanoscience and Technology, University of Chinese Academy of Sciences, Sichuan University, West China Medical Center of Sichuan University, West China Hospital of Sichuan University
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,643
OpenAlex ID: W4405848529