ArticleProceedings of the National Academy of Sciences of the United States of America2023
Defining a de novo non-RBM antibody as RBD-8 and its synergistic rescue of immune-evaded antibodies to neutralize Omicron SARS-CoV-2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 34 citations in OpenAlex.
- Monoclonal antibodies from COVID-19 convalescent patients target cryptic epitopes for broad SARS-CoV-2 neutralization.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- SARS-CoV-2 Spike Protein XBB.1.5 Mutations Altered Four Conserved Antigenic Determinants.International journal of molecular sciences · 2026Article
- Article
- Broadly Sarbecovirus-Neutralizing Antibodies Induced by Ancestral SARS-CoV-2 Infection.Viruses · 2025Article
- Broad neutralizing antibody response of a monomeric spike-based SARS-CoV-2 bivalent vaccine against diverse variants.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Discovery of Synergistic Broadly Neutralizing Antibodies Targeting Non-Dominant Epitopes on SARS-CoV-2 RBD and NTD.Vaccines · 2025Article
- Early 2022 breakthrough infection sera from India target the conserved cryptic class 5 epitope to counteract immune escape by SARS-CoV-2 variants.Journal of virology · 2025Article
- A high-throughput, fully automated competition assay to evaluate SARS-CoV-2 neutralizing responses and epitope specificity in clinical samples.Scientific reports · 2025Article
- Affinity maturation endows potent activity onto class 6 SARS-CoV-2 broadly neutralizing antibodies.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Excessive accumulation of auxin inhibits protocorm development during germination of Paphiopedilum spicerianum.Plant cell reports · 2025Article
- Structural Immunology of SARS-CoV-2.Immunological reviews · 2025Review
- Broadening sarbecovirus neutralization with bispecific antibodies combining distinct conserved targets on the receptor binding domain.Human vaccines & immunotherapeutics · 2024Article
- Facilitating and restraining virus infection using cell-attachable soluble viral receptors.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The binding and structural basis of fox ACE2 to RBDs from different sarbecoviruses.Virologica Sinica · 2024Article
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Authors and funding
25 authors at 8 institutions in 2 countries.
Funding
Abstract
Currently, monoclonal antibodies (MAbs) targeting the SARS-CoV-2 receptor binding domain (RBD) of spike (S) protein are classified into seven classes based on their binding epitopes. However, most of these antibodies are seriously impaired by SARS-CoV-2 Omicron and its subvariants, especially the recent BQ.1.1, XBB and its derivatives. Identification of broadly neutralizing MAbs against currently circulating variants is imperative. In this study, we identified a "breathing" cryptic epitope in the S protein, named as RBD-8. Two human MAbs, BIOLS56 and IMCAS74, were isolated recognizing this epitope with broad neutralization abilities against tested sarbecoviruses, including SARS-CoV, pangolin-origin coronaviruses, and all the SARS-CoV-2 variants tested (Omicron BA.4/BA.5, BQ.1.1, and XBB subvariants). Searching through the literature, some more RBD-8 MAbs were defined. More importantly, BIOLS56 rescues the immune-evaded antibody, RBD-5 MAb IMCAS-L4.65, by making a bispecific MAb, to neutralize BQ.1 and BQ.1.1, thereby producing an MAb to cover all the currently circulating Omicron subvariants. Structural analysis reveals that the neutralization effect of RBD-8 antibodies depends on the extent of epitope exposure, which is affected by the angle of antibody binding and the number of up-RBDs induced by angiotensin-converting enzyme 2 binding. This cryptic epitope which recognizes non- receptor binding motif (non-RBM) provides guidance for the development of universal therapeutic antibodies and vaccines against COVID-19.
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