Related Experiment Video
Updated: Jul 16, 2025
Protocol for Recombinant RBD-based SARS Vaccines: Protein Preparation, Animal Vaccination and Neutralization Detection
Published on: May 2, 2011
Broadly neutralizing antibodies derived from the earliest COVID-19 convalescents protect mice from SARS-CoV-2
Qianyun Liu1,2, Haiyan Zhao1, Zhiqiang Li3
1State Key Laboratory of Virology, Institute for Vaccine Research, College of Life Sciences, Wuhan University, Wuhan, 430072, China.
Insights
Elite COVID-19 convalescents produced potent monoclonal antibodies (mAbs) that neutralize SARS-CoV-2 variants, including Omicron. These human mAbs offer potential prophylactic and therapeutic benefits against diverse coronavirus strains.
Area of Science:
- Immunology and Virology
Background:
- The emergence of SARS-CoV-2 variants of concern (VOCs) poses a continuous threat, necessitating the development of broadly effective countermeasures.
- Vaccines were developed based on the original SARS-CoV-2 strain, but viral evolution has led to immune escape.
Purpose of the Study:
- To isolate and characterize human monoclonal antibodies (mAbs) from individuals who recovered from the original SARS-CoV-2 infection.
- To evaluate the neutralizing activity of these mAbs against various SARS-CoV-2 strains, including VOCs and Omicron subvariants.
- To assess the in vivo prophylactic and therapeutic efficacy of the most potent mAbs.
Main Methods:
- Isolation of six human mAbs from two elite convalescents in Wuhan.
- In vitro neutralization assays against SARS-CoV-2 original strain and VOCs (including Omicron XBB and XBB.1.5).
- In vivo studies in K18-hACE2 KI mice to evaluate prophylactic and therapeutic effects against SARS-CoV-2 WT, Delta, and Omicron variants.
- Cryo-electron microscopy (Cryo-EM) to determine the binding epitopes and mechanism of neutralization.
Main Results:
- Six human mAbs were developed, recognizing diverse epitopes on the SARS-CoV-2 receptor binding domain (RBD).
- These mAbs demonstrated varying degrees of inhibition against the original strain and VOCs, including Omicron XBB and XBB.1.5.
- Two mAbs, 7B3 and 14B1, showed potent broad neutralization, prophylactic activity against WT, and therapeutic effects against Delta and Omicron variants in mice.
- Cryo-EM revealed that 7B3 and 14B1 bind overlapping epitopes on the RBD, sterically hindering hACE2 binding.
Conclusions:
- Elite COVID-19 convalescents harbor mAbs with broad neutralizing activity against diverse SARS-CoV-2 strains, including immune-evasive variants.
- These findings highlight the potential of naturally derived mAbs as therapeutic and prophylactic agents against current and future SARS-CoV-2 threats.
- The study underscores the lasting benefit of prior infection or vaccination despite viral evolution and immune escape.
Abstract:
Coronavirus disease 2019 (COVID-19) was first reported three years ago, when a group of individuals were infected with the original SARS-CoV-2 strain, based on which vaccines were developed. Here, we develop six human monoclonal antibodies (mAbs) from two elite convalescents in Wuhan and show that these mAbs recognize diverse epitopes on the receptor binding domain (RBD) and can inhibit the infection of SARS-CoV-2 original strain and variants of concern (VOCs) to varying degrees, including Omicron strains XBB and XBB.1.5. Of these mAbs, the two most broadly and potently neutralizing mAbs (7B3 and 14B1) exhibit prophylactic activity against SARS-CoV-2 WT infection and therapeutic effects against SARS-CoV-2 Delta variant challenge in K18-hACE2 KI mice. Furthermore, post-exposure treatment with 7B3 protects mice from lethal Omicron variants infection. Cryo-EM analysis of the spike trimer complexed with 14B1 or 7B3 reveals that these two mAbs bind partially overlapped epitopes onto the RBD of the spike, and sterically disrupt the binding of human angiotensin-converting enzyme 2 (hACE2) to RBD. Our results suggest that mAbs with broadly neutralizing activity against different SARS-CoV-2 variants are present in COVID-19 convalescents infected by the ancestral SARS-CoV-2 strain, indicating that people can benefit from former infections or vaccines despite the extensive immune escape of SARS-CoV-2.
More Related Videos
10:25Detection of SARS-CoV-2 Neutralizing Antibodies using High-Throughput Fluorescent Imaging of Pseudovirus Infection
Published on: June 5, 2021
08:41Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
Published on: November 5, 2021