For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
31
views
10
references
 Top references
cited by
62
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
1 collections
    0
    shares
      258
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

      Antigenic evolution will lead to new SARS-CoV-2 variants with unpredictable severity

      brief-report

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The comparatively milder infections with the Omicron variant and higher levels of population immunity have raised hopes for a weakening of the pandemic. We argue that the lower severity of Omicron is a coincidence and that ongoing rapid antigenic evolution is likely to produce new variants that may escape immunity and be more severe.

          Related collections

          Most cited references10

          • Record: found
          • Abstract: found
          • Article: not found

          SARS-CoV-2 variants, spike mutations and immune escape

          William T. Harvey, Alessandro M. Carabelli, Ben Jackson … (2021)
          Although most mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome are expected to be either deleterious and swiftly purged or relatively neutral, a small proportion will affect functional properties and may alter infectivity, disease severity or interactions with host immunity. The emergence of SARS-CoV-2 in late 2019 was followed by a period of relative evolutionary stasis lasting about 11 months. Since late 2020, however, SARS-CoV-2 evolution has been characterized by the emergence of sets of mutations, in the context of ‘variants of concern’, that impact virus characteristics, including transmissibility and antigenicity, probably in response to the changing immune profile of the human population. There is emerging evidence of reduced neutralization of some SARS-CoV-2 variants by postvaccination serum; however, a greater understanding of correlates of protection is required to evaluate how this may impact vaccine effectiveness. Nonetheless, manufacturers are preparing platforms for a possible update of vaccine sequences, and it is crucial that surveillance of genetic and antigenic changes in the global virus population is done alongside experiments to elucidate the phenotypic impacts of mutations. In this Review, we summarize the literature on mutations of the SARS-CoV-2 spike protein, the primary antigen, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets. The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been characterized by the emergence of mutations and so-called variants of concern that impact virus characteristics, including transmissibility and antigenicity. In this Review, members of the COVID-19 Genomics UK (COG-UK) Consortium and colleagues summarize mutations of the SARS-CoV-2 spike protein, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets.
          Article 0 comments Cited 1579 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity

            Bo Meng, Adam Abdullahi, Isabella Ferreira … (2022)
            The SARS-CoV-2 Omicron BA.1 variant emerged in 2021 1 and has multiple mutations in its spike protein 2 . Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis of spike-pseudotyped virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and deletion of TMPRSS2 affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways3 demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis.
            Article 0 comments Cited 472 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The biological and clinical significance of emerging SARS-CoV-2 variants

              Kaiming Tao, Philip Tzou, Janin Nouhin … (2021)
              The past several months have witnessed the emergence of SARS-CoV-2 variants with novel spike protein mutations that are influencing the epidemiological and clinical aspects of the COVID-19 pandemic. These variants can increase rates of virus transmission and/or increase the risk of reinfection and reduce the protection afforded by neutralizing monoclonal antibodies and vaccination. These variants can therefore enable SARS-CoV-2 to continue its spread in the face of rising population immunity while maintaining or increasing its replication fitness. The identification of four rapidly expanding virus lineages since December 2020, designated variants of concern, has ushered in a new stage of the pandemic. The four variants of concern, the Alpha variant (originally identified in the UK), the Beta variant (originally identified in South Africa), the Gamma variant (originally identified in Brazil) and the Delta variant (originally identified in India), share several mutations with one another as well as with an increasing number of other recently identified SARS-CoV-2 variants. Collectively, these SARS-CoV-2 variants complicate the COVID-19 research agenda and necessitate additional avenues of laboratory, epidemiological and clinical research. In this Review, the authors describe our latest understanding of the emergence and properties of SARS-CoV-2 genetic variants, particularly those designated as WHO (World Health Organization) ‘variants of concern’. They focus on the consequences of these variants for antibody-mediated virus neutralization, with important implications for reinfection risk and for vaccine effectiveness. The past several months have witnessed the emergence of four SARS-CoV-2 variants of concern (Alpha, Beta, Gamma and Delta) associated with increased transmissibility, increased risk of reinfection and/or reduced vaccine efficacy. Many additional SARS-CoV-2 variants sharing mutations and biological features with these variants are also increasingly being identified. The increasing number of SARS-CoV-2 variants share a repertoire of mutations that is enabling the virus to spread despite rising population immunity while maintaining or increasing its replication fitness. Whereas most emerging mutations reduce the protective effects of neutralizing antibodies generated by infection and vaccination, several recently identified mutations appear to antagonize the innate immune response to initial infection. The emergence of SARS-CoV-2 variants requires an expanded research agenda to improve our understanding of emerging SARS-CoV-2 mutations and the correlates of protective immunity against variants with these mutations.
              Article 0 comments Cited 466 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Peter V. Markov: peter.markov@ec.europa.eu
                Journal
                Journal ID (nlm-ta): Nat Rev Microbiol
                Journal ID (iso-abbrev): Nat Rev Microbiol
                Title: Nature Reviews. Microbiology
                Publisher: Nature Publishing Group UK (London )
                ISSN (Print): 1740-1526
                ISSN (Electronic): 1740-1534
                Publication date (Electronic): 14 March 2022
                Pages: 1-2
                Affiliations
                [1 ]GRID grid.434554.7, ISNI 0000 0004 1758 4137, European Commission, Joint Research Centre (JRC), ; Ispra, Italy
                [2 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Department of Zoology, , University of Oxford, ; Oxford, UK
                [3 ]GRID grid.5330.5, ISNI 0000 0001 2107 3311, Department of Biometry and Epidemiology, , University of Erlangen-Nuremberg, ; Erlangen, Germany
                Article
                Publisher ID: 722
                DOI: 10.1038/s41579-022-00722-z
                PMC ID: 8919145
                PubMed ID: 35288685
                SO-VID: feeb159a-d9ac-4513-a32c-0a99c42faae4
                Copyright © © Springer Nature Limited 2022
                License:

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                Categories
                Subject: Comment

                Keywords: epidemiology,viral evolution,vaccines,viral immune evasion,sars-cov-2
                Data availability:
                Keywords: epidemiology, viral evolution, vaccines, viral immune evasion, sars-cov-2

                Comments

                Comment on this article

                scite_

                Similar content258

                See all similar

                Cited by62

                See all cited by

                Most referenced authors965

                See all reference authors