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      Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection

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          Abstract

          More than one year after its inception, the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains difficult to control despite the availability of several working vaccines. Progress in controlling the pandemic is slowed by the emergence of variants that appear to be more transmissible and more resistant to antibodies 1, 2 . Here we report on a cohort of 63 individuals who have recovered from COVID-19 assessed at 1.3, 6.2 and 12 months after SARS-CoV-2 infection, 41% of whom also received mRNA vaccines 3, 4 . In the absence of vaccination, antibody reactivity to the receptor binding domain (RBD) of SARS-CoV-2, neutralizing activity and the number of RBD-specific memory B cells remain relatively stable between 6 and 12 months after infection. Vaccination increases all components of the humoral response and, as expected, results in serum neutralizing activities against variants of concern similar to or greater than the neutralizing activity against the original Wuhan Hu-1 strain achieved by vaccination of naive individuals 2, 58 . The mechanism underlying these broad-based responses involves ongoing antibody somatic mutation, memory B cell clonal turnover and development of monoclonal antibodies that are exceptionally resistant to SARS-CoV-2 RBD mutations, including those found in the variants of concern 4, 9 . In addition, B cell clones expressing broad and potent antibodies are selectively retained in the repertoire over time and expand markedly after vaccination. The data suggest that immunity in convalescent individuals will be very long lasting and that convalescent individuals who receive available mRNA vaccines will produce antibodies and memory B cells that should be protective against circulating SARS-CoV-2 variants.

          Abstract

          Antibodies against SARS-CoV-2 continue to evolve 6 to 12 months after infection in patients who have recovered from COVID-19, increasing in potency and breadth with time.

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          SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

          Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
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            A new coronavirus associated with human respiratory disease in China

            Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health 1–3 . Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing 4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here ‘WH-Human 1’ coronavirus (and has also been referred to as ‘2019-nCoV’). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China 5 . This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.
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              Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.

              A new method of total RNA isolation by a single extraction with an acid guanidinium thiocyanate-phenol-chloroform mixture is described. The method provides a pure preparation of undegraded RNA in high yield and can be completed within 4 h. It is particularly useful for processing large numbers of samples and for isolation of RNA from minute quantities of cells or tissue samples.
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                Author and article information

                Contributors
                pbieniasz@rockefeller.edu
                mcaskey@rockefeller.edu
                thatziio@rockefeller.edu
                nussen@rockefeller.edu
                Journal
                Nature
                Nature
                Nature
                Nature Publishing Group UK (London )
                0028-0836
                1476-4687
                14 June 2021
                14 June 2021
                2021
                : 595
                : 7867
                : 426-431
                Affiliations
                [1 ]GRID grid.134907.8, ISNI 0000 0001 2166 1519, Laboratory of Molecular Immunology, , The Rockefeller University, ; New York, NY USA
                [2 ]GRID grid.134907.8, ISNI 0000 0001 2166 1519, Laboratory of Retrovirology, , The Rockefeller University, ; New York, NY USA
                [3 ]GRID grid.134907.8, ISNI 0000 0001 2166 1519, Laboratory of Virology and Infectious Disease, , The Rockefeller University, ; New York, NY USA
                [4 ]GRID grid.20861.3d, ISNI 0000000107068890, Division of Biology and Biological Engineering, , California Institute of Technology, ; Pasadena, CA USA
                [5 ]GRID grid.5386.8, ISNI 000000041936877X, Department of Pathology and Laboratory Medicine, , Weill Cornell Medicine, ; New York, NY USA
                [6 ]GRID grid.413575.1, ISNI 0000 0001 2167 1581, Howard Hughes Medical Institute, ; New York, NY USA
                Author information
                http://orcid.org/0000-0002-0132-5101
                http://orcid.org/0000-0002-5380-2950
                http://orcid.org/0000-0003-4474-2658
                http://orcid.org/0000-0001-7295-8128
                http://orcid.org/0000-0001-7353-3420
                http://orcid.org/0000-0002-2654-0879
                http://orcid.org/0000-0002-0036-4803
                http://orcid.org/0000-0003-1595-6585
                http://orcid.org/0000-0001-9640-0559
                http://orcid.org/0000-0003-2247-3178
                http://orcid.org/0000-0002-9742-5982
                http://orcid.org/0000-0002-2368-3719
                http://orcid.org/0000-0003-1727-8693
                http://orcid.org/0000-0002-7889-0766
                http://orcid.org/0000-0003-0592-8564
                Article
                3696
                10.1038/s41586-021-03696-9
                8277577
                34126625
                b8626584-000e-4461-9dfc-d67f300b8a8e
                © 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
                : 2 May 2021
                : 4 June 2021
                Categories
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                Custom metadata
                © The Author(s), under exclusive licence to Springer Nature Limited 2021

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

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