ArticleJournal of virology2021
SARS-CoV-2 Spike Protein Stabilized in the Closed State Induces Potent Neutralizing Responses.
Article in Journal of virology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Saliva is suitable for SARS-CoV-2 antibodies detection after vaccination: A rapid systematic review.Frontiers in immunology · 2022Pooled it
- Structural basis for sarbecovirus Rc-o319 spike adaptation to Rhinolophus cornutus Bat ACE2 and constraints on switching to human ACE2.PLoS pathogens · 2026Article
- AI-guided prefusion stabilization of the human coronavirus OC43 spike protein enables universal embecovirus antigen design.PLoS pathogens · 2026Article
- Neutralization and ADCC reveal divergent spike-subdomain targeting across SARS-CoV-2 vaccine platforms in an African cohort.iScience · 2026Article
- Computationally designed haemagglutinin with nanocage plug-and-display elicits pan-H5 influenza vaccine responses.Emerging microbes & infections · 2025Article
- Molecular mechanisms of SARS-CoV-2 entry: implications for biomedical strategies.Microbiology and molecular biology reviews : MMBR · 2025Review
- SARS-related coronavirus S-protein structures reveal synergistic RBM interactions underpinning high-affinity human ACE2 binding.Science advances · 2025Article
- The immunological impact of revaccination in a hybrid-immune world.Frontiers in immunology · 2025Review
- Stoichiometric insights into SARS-CoV-2 spike-ACE2 binding across variants.Computational and structural biotechnology journal · 2025Article
- Characterization of a neutralizing antibody that recognizes a loop region adjacent to the receptor-binding interface of the SARS-CoV-2 spike receptor-binding domain.Microbiology spectrum · 2024Article
- Impact of SARS-CoV-2 spike stability and RBD exposure on antigenicity and immunogenicity.Scientific reports · 2024Article
- S6P mutation in Delta and Omicron variant spike protein significantly enhances the efficacy of mRNA COVID-19 vaccines.Frontiers in immunology · 2024Article
- Review
- Cross-protection and cross-neutralization capacity of ancestral and VOC-matched SARS-CoV-2 adenoviral vector-based vaccines.NPJ vaccines · 2023Article
- Article
- Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes.Life science alliance · 2023Article
- 'Spikeopathy': COVID-19 Spike Protein Is Pathogenic, from Both Virus and Vaccine mRNA.Biomedicines · 2023Review
- Design and Immunogenicity of SARS-CoV-2 DNA Vaccine Encoding RBD-PVXCP Fusion Protein.Vaccines · 2023Article
- Incorporation of SARS-CoV-2 spike NTD to RBD protein vaccine improves immunity against viral variants.iScience · 2023Article
- Glycan masking of a non-neutralising epitope enhances neutralising antibodies targeting the RBD of SARS-CoV-2 and its variants.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
The majority of SARS-CoV-2 vaccines in use or advanced development are based on the viral spike protein (S) as their immunogen. S is present on virions as prefusion trimers in which the receptor binding domain (RBD) is stochastically open or closed. Neutralizing antibodies have been described against both open and closed conformations. The long-term success of vaccination strategies depends upon inducing antibodies that provide long-lasting broad immunity against evolving SARS-CoV-2 strains. Here, we have assessed the results of immunization in a mouse model using an S protein trimer stabilized in the closed state to prevent full exposure of the receptor binding site and therefore interaction with the receptor. We compared this with other modified S protein constructs, including representatives used in current vaccines. We found that all trimeric S proteins induced a T cell response and long-lived, strongly neutralizing antibody responses against 2019 SARS-CoV-2 and variants of concern P.1 and B.1.351. Notably, the protein binding properties of sera induced by the closed spike differed from those induced by standard S protein constructs. Closed S proteins induced more potent neutralizing responses than expected based on the degree to which they inhibit interactions between the RBD and ACE2. These observations suggest that closed spikes recruit different, but equally potent, immune responses than open spikes and that this is likely to include neutralizing antibodies against conformational epitopes present in the closed conformation. We suggest that closed spikes, together with their improved stability and storage properties, may be a valuable component of refined, next-generation vaccines.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.