ArticleEBioMedicine2022
Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern.
Article in EBioMedicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Integration of a novel anti-PD-1 antibody with chimeric antigen receptor-T engineered to express interleukin-7 enhances targeting efficacy against lung cancer.Life medicine · 2025Article
- T-Cell-Dependent Bispecific IgGs Protect Aged Mice From Lethal SARS-CoV-2 Infection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Impact of immunodeficiencies on immunity induced by SARS-CoV-2 infection, mRNA BNT162b2 vaccination, and their combination in children and young adults.Frontiers in immunology · 2025Article
- Lactoferrin Binds through Its N-Terminus to the Receptor-Binding Domain of the SARS-CoV-2 Spike Protein.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Angiotensin I and II Stimulate Cell Invasion of SARS-CoV-2: Potential Mechanism via Inhibition of ACE2 Arm of RAS.Physiological research · 2024Article
- Blood-brain barrier penetration of non-replicating SARS-CoV-2 and S1 variants of concern induce neuroinflammation which is accentuated in a mouse model of Alzheimer's disease.Brain, behavior, and immunity · 2023Article
- State of the art in epitope mapping and opportunities in COVID-19.Future science OA · 2023Review
- Long-Term Vaccination and Treatment Strategies for COVID-19 Disease and Future Coronavirus Pandemics.Advances in experimental medicine and biology · 2023Review
- Sensitivity to Vaccines, Therapeutic Antibodies, and Viral Entry Inhibitors and Advances To Counter the SARS-CoV-2 Omicron Variant.Clinical microbiology reviews · 2022Review
- Review
- Immune Escape Associated with RBD Omicron Mutations and SARS-CoV-2 Evolution Dynamics.Viruses · 2022Review
- Potential for a Plant-Made SARS-CoV-2 Neutralizing Monoclonal Antibody as a Synergetic Cocktail Component.Vaccines · 2022Article
- Blockade of TMPRSS2-mediated priming of SARS-CoV-2 by lactoferricin.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
45 authors at 9 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe emergence of new SARS-CoV-2 variants of concern B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma) and B.1.617.2 (Delta) that harbor mutations in the viral S protein raised concern about activity of current vaccines and therapeutic antibodies. Independent studies have shown that mutant variants are partially or completely resistant against some of the therapeutic antibodies authorized for emergency use.
methodsWe employed hybridoma technology, ELISA-based and cell-based S-ACE2 interaction assays combined with authentic virus neutralization assays to develop second-generation antibodies, which were specifically selected for their ability to neutralize the new variants of SARS-CoV-2.
findingsAX290 and AX677, two monoclonal antibodies with non-overlapping epitopes, exhibit subnanomolar or nanomolar affinities to the receptor binding domain of the viral Spike protein carrying amino acid substitutions N501Y, N439K, E484K, K417N, and a combination N501Y/E484K/K417N found in the circulating virus variants. The antibodies showed excellent neutralization of an authentic SARS-CoV-2 virus representing strains circulating in Europe in spring 2020 and also the variants of concern B.1.1.7 (Alpha), B.1.351 (Beta) and B.1.617.2 (Delta). In addition, AX677 is able to bind Omicron Spike protein just like the wild type Spike. The combination of the two antibodies prevented the appearance of escape mutations of the authentic SARS-CoV-2 virus. Prophylactic administration of AX290 and AX677, either individually or in combination, effectively reduced viral burden and inflammation in the lungs, and prevented disease in a mouse model of SARS-CoV-2 infection.
interpretationThe virus-neutralizing properties were fully reproduced in chimeric mouse-human versions of the antibodies, which may represent a promising tool for COVID-19 therapy.
fundingThe study was funded by AXON Neuroscience SE and AXON COVIDAX a.s.
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