68
views
0
recommends
+1 Recommend
3 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization

      research-article
      1 , 2 , 1 , 3 , 1 , 2 , 4 , 5 , 6 , 7 , 6 , 3 , 4 , 5 , 2 , 4 , 1 , 2 , 1 , 8 , 8 , 9 , 10 , 1 , 1 , 1 , 1 , 11 , 6 , 10 , 12 , 13 , 8 , 14 , 1 , 11 , NGS-SA, COMMIT-KZN Team, 4 , 5 , 4 , 5 , 6 , 8 , 13 , 3 , 6 , 7 , 8 , 15 , 4 , 5 , 8 , 12 , 1 , 2 , 16 ,
      Nature
      Nature Publishing Group UK
      SARS-CoV-2, Antimicrobial responses

      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 emergence of the SARS-CoV-2 variant of concern Omicron (Pango lineage B.1.1.529), first identified in Botswana and South Africa, may compromise vaccine effectiveness and lead to re-infections 1 . Here we investigated Omicron escape from neutralization by antibodies from South African individuals vaccinated with Pfizer BNT162b2. We used blood samples taken soon after vaccination from individuals who were vaccinated and previously infected with SARS-CoV-2 or vaccinated with no evidence of previous infection. We isolated and sequence-confirmed live Omicron virus from an infected person and observed that Omicron requires the angiotensin-converting enzyme 2 (ACE2) receptor to infect cells. We compared plasma neutralization of Omicron relative to an ancestral SARS-CoV-2 strain and found that neutralization of ancestral virus was much higher in infected and vaccinated individuals compared with the vaccinated-only participants. However, both groups showed a 22-fold reduction in vaccine-elicited neutralization by the Omicron variant. Participants who were vaccinated and had previously been infected exhibited residual neutralization of Omicron similar to the level of neutralization of the ancestral virus observed in the vaccination-only group. These data support the notion that reasonable protection against Omicron may be maintained using vaccination approaches.

          Abstract

          Plasma from individuals vaccinated with BNT162b2 exhibits 22-fold less neutralization capacity against Omicron (B.1.1.529) than against an ancestral SARS-CoV-2 strain but residual neutralization is maintained in those with high levels of neutralization of ancestral virus.

          Related collections

          Most cited references28

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

          Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection

          Predictive models of immune protection from COVID-19 are urgently needed to identify correlates of protection to assist in the future deployment of vaccines. To address this, we analyzed the relationship between in vitro neutralization levels and the observed protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using data from seven current vaccines and from convalescent cohorts. We estimated the neutralization level for 50% protection against detectable SARS-CoV-2 infection to be 20.2% of the mean convalescent level (95% confidence interval (CI) = 14.4-28.4%). The estimated neutralization level required for 50% protection from severe infection was significantly lower (3% of the mean convalescent level; 95% CI = 0.7-13%, P = 0.0004). Modeling of the decay of the neutralization titer over the first 250 d after immunization predicts that a significant loss in protection from SARS-CoV-2 infection will occur, although protection from severe disease should be largely retained. Neutralization titers against some SARS-CoV-2 variants of concern are reduced compared with the vaccine strain, and our model predicts the relationship between neutralization and efficacy against viral variants. Here, we show that neutralization level is highly predictive of immune protection, and provide an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

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

            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.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7

              The COVID-19 pandemic has had widespread effects across the globe, and its causative agent, SARS-CoV-2, continues to spread. Effective interventions need to be developed to end this pandemic. Single and combination therapies with monoclonal antibodies have received emergency use authorization1-3, and more treatments are under development4-7. Furthermore, multiple vaccine constructs have shown promise8, including two that have an approximately 95% protective efficacy against COVID-199,10. However, these interventions were directed against the initial SARS-CoV-2 virus that emerged in 2019. The recent detection of SARS-CoV-2 variants B.1.1.7 in the UK11 and B.1.351 in South Africa12 is of concern because of their purported ease of transmission and extensive mutations in the spike protein. Here we show that B.1.1.7 is refractory to neutralization by most monoclonal antibodies against the N-terminal domain of the spike protein and is relatively resistant to a few monoclonal antibodies against the receptor-binding domain. It is not more resistant to plasma from individuals who have recovered from COVID-19 or sera from individuals who have been vaccinated against SARS-CoV-2. The B.1.351 variant is not only refractory to neutralization by most monoclonal antibodies against the N-terminal domain but also by multiple individual monoclonal antibodies against the receptor-binding motif of the receptor-binding domain, which is mostly due to a mutation causing an E484K substitution. Moreover, compared to wild-type SARS-CoV-2, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4-fold) and sera from individuals who have been vaccinated (10.3-12.4-fold). B.1.351 and emergent variants13,14 with similar mutations in the spike protein present new challenges for monoclonal antibody therapies and threaten the protective efficacy of current vaccines.
                Bookmark

                Author and article information

                Contributors
                alex.sigal@ahri.org
                Journal
                Nature
                Nature
                Nature
                Nature Publishing Group UK (London )
                0028-0836
                1476-4687
                23 December 2021
                23 December 2021
                2022
                : 602
                : 7898
                : 654-656
                Affiliations
                [1 ]GRID grid.488675.0, ISNI 0000 0004 8337 9561, Africa Health Research Institute, ; Durban, South Africa
                [2 ]GRID grid.16463.36, ISNI 0000 0001 0723 4123, School of Laboratory Medicine and Medical Sciences, , University of KwaZulu-Natal, ; Durban, South Africa
                [3 ]GRID grid.1005.4, ISNI 0000 0004 4902 0432, Kirby Institute, , University of New South Wales, ; Sydney, New South Wales Australia
                [4 ]GRID grid.416657.7, ISNI 0000 0004 0630 4574, National Institute for Communicable Diseases of the National Health Laboratory Service, ; Johannesburg, South Africa
                [5 ]GRID grid.11951.3d, ISNI 0000 0004 1937 1135, SA MRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, , University of the Witwatersrand, ; Johannesburg, South Africa
                [6 ]KwaZulu-Natal Research Innovation and Sequencing Platform, Durban, South Africa
                [7 ]GRID grid.11956.3a, ISNI 0000 0001 2214 904X, Centre for Epidemic Response and Innovation, School of Data Science and Computational Thinking, , Stellenbosch University, ; Stellenbosch, South Africa
                [8 ]GRID grid.428428.0, ISNI 0000 0004 5938 4248, Centre for the AIDS Programme of Research in South Africa, ; Durban, South Africa
                [9 ]GRID grid.16463.36, ISNI 0000 0001 0723 4123, Department of Medical Microbiology, , University of KwaZulu-Natal, ; Durban, South Africa
                [10 ]GRID grid.7836.a, ISNI 0000 0004 1937 1151, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, , University of Cape Town, ; Cape Town, South Africa
                [11 ]GRID grid.83440.3b, ISNI 0000000121901201, Division of Infection and Immunity, , University College London, ; London, UK
                [12 ]GRID grid.7836.a, ISNI 0000 0004 1937 1151, Institute of Infectious Disease and Molecular Medicine, , University of Cape Town, ; Cape Town, South Africa
                [13 ]GRID grid.16463.36, ISNI 0000 0001 0723 4123, Department of Infectious Diseases, Nelson R. Mandela School of Clinical Medicine, , University of KwaZulu-Natal, ; Durban, South Africa
                [14 ]GRID grid.21729.3f, ISNI 0000000419368729, Department of Epidemiology, Mailman School of Public Health, , Columbia University, ; New York, NY USA
                [15 ]GRID grid.34477.33, ISNI 0000000122986657, Department of Global Health, , University of Washington, ; Seattle, WA USA
                [16 ]GRID grid.418159.0, ISNI 0000 0004 0491 2699, Max Planck Institute for Infection Biology, ; Berlin, Germany
                [17 ]GRID grid.7836.a, ISNI 0000 0004 1937 1151, Center for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, , University of Cape Town, ; Cape Town, South Africa
                [18 ]GRID grid.7836.a, ISNI 0000 0004 1937 1151, University of Cape Town/Groote Schuur Complex of the National Health Laboratory Service (NHLS), University of Cape Town, ; Cape Town, South Africa
                [19 ]GRID grid.7836.a, ISNI 0000 0004 1937 1151, Division of Computational Biology, Department of Integrative Biomedical Sciences, , University of Cape Town, ; Cape Town, South Africa
                [20 ]GRID grid.16463.36, ISNI 0000 0001 0723 4123, Medical Microbiology Department, , University of KwaZulu-Natal, ; Durban, South Africa
                [21 ]National Health Laboratory Services (NHLS), Durban, South Africa
                [22 ]GRID grid.7836.a, ISNI 0000 0004 1937 1151, Wellcome Centre for Infectious Diseases Research in Africa, , University of Cape Town, ; Cape Town, South Africa
                [23 ]GRID grid.511287.8, Molecular Diagnostics Services, ; Durban, South Africa
                [24 ]GRID grid.16463.36, ISNI 0000 0001 0723 4123, Department of Neurosurgery, , University of KwaZulu-Natal, ; Durban, South Africa
                [25 ]South African Population Research Infrastructure Network, Durban, South Africa
                [26 ]GRID grid.16463.36, ISNI 0000 0001 0723 4123, Department of Paediatrics and Child Health, , University of KwaZulu-Natal, ; Durban, South Africa
                [27 ]GRID grid.5254.6, ISNI 0000 0001 0674 042X, Department of Immunology and Microbiology, , University of Copenhagen, ; Copenhagen, Denmark
                [28 ]GRID grid.16463.36, ISNI 0000 0001 0723 4123, Department of Cardiothoracic Surgery, , University of KwaZulu-Natal, ; Durban, South Africa
                [29 ]GRID grid.415293.8, ISNI 0000 0004 0383 9602, Department of Medicine, , King Edward VIII Hospital and University of KwaZulu Natal, ; Durban, South Africa
                [30 ]GRID grid.16463.36, ISNI 0000 0001 0723 4123, College of Health Sciences, , University of KwaZulu-Natal, ; Durban, South Africa
                [31 ]GRID grid.461656.6, ISNI 0000 0004 0489 3491, Ragon Institute of MGH, MIT and Harvard, ; Boston, MA USA
                [32 ]GRID grid.16463.36, ISNI 0000 0001 0723 4123, HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, , University of KwaZulu-Natal, ; Durban, South Africa
                [33 ]GRID grid.16463.36, ISNI 0000 0001 0723 4123, Department of Pulmonology and Critical Care, , University of KwaZulu-Natal, ; Durban, South Africa
                [34 ]GRID grid.16463.36, ISNI 0000 0001 0723 4123, Department of Neurology, , University of KwaZulu-Natal, ; Durban, South Africa
                [35 ]GRID grid.265892.2, ISNI 0000000106344187, Division of Infectious Diseases, , University of Alabama at Birmingham, ; Birmingham, AL USA
                Author information
                http://orcid.org/0000-0002-1516-3270
                http://orcid.org/0000-0002-5648-9808
                http://orcid.org/0000-0001-8988-9595
                http://orcid.org/0000-0002-6336-7489
                http://orcid.org/0000-0001-6354-4003
                http://orcid.org/0000-0001-8719-4028
                http://orcid.org/0000-0001-8571-2004
                Article
                4387
                10.1038/s41586-021-04387-1
                8866126
                35016196
                7a0d263d-f1d3-4bc4-9b7e-9451a4bd14e7
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 14 December 2021
                : 23 December 2021
                Categories
                Article
                Custom metadata
                © The Author(s), under exclusive licence to Springer Nature Limited 2022

                Uncategorized
                sars-cov-2,antimicrobial responses
                Uncategorized
                sars-cov-2, antimicrobial responses

                Comments

                Comment on this article