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      Evolutionary implications of SARS-CoV-2 vaccination for the future design of vaccination strategies

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          Abstract

          Once the first SARS-CoV-2 vaccine became available, mass vaccination was the main pillar of the public health response to the COVID-19 pandemic. It was very effective in reducing hospitalizations and deaths. Here, we discuss the possibility that mass vaccination might accelerate SARS-CoV-2 evolution in antibody-binding regions compared to natural infection at the population level. Using the evidence of strong genetic variation in antibody-binding regions and taking advantage of the similarity between the envelope proteins of SARS-CoV-2 and influenza, we assume that immune selection pressure acting on these regions of the two viruses is similar. We discuss the consequences of this assumption for SARS-CoV-2 evolution in light of mathematical models developed previously for influenza. We further outline the implications of this phenomenon, if our assumptions are confirmed, for the future design of SARS-CoV-2 vaccination strategies.

          Abstract

          Rouzine and Rozhnova discuss the potential consequences of vaccination on the antigenic evolution of the SARS-CoV-2 virus. The authors outline the possibility of its acceleration by mass vaccination and considerations for future vaccination strategies.

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          Most cited references135

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          Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period

          It is urgent to understand the future of severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) transmission. We used estimates of seasonality, immunity, and cross-immunity for betacoronaviruses OC43 and HKU1 from time series data from the USA to inform a model of SARS-CoV-2 transmission. We projected that recurrent wintertime outbreaks of SARS-CoV-2 will probably occur after the initial, most severe pandemic wave. Absent other interventions, a key metric for the success of social distancing is whether critical care capacities are exceeded. To avoid this, prolonged or intermittent social distancing may be necessary into 2022. Additional interventions, including expanded critical care capacity and an effective therapeutic, would improve the success of intermittent distancing and hasten the acquisition of herd immunity. Longitudinal serological studies are urgently needed to determine the extent and duration of immunity to SARS-CoV-2. Even in the event of apparent elimination, SARS-CoV-2 surveillance should be maintained since a resurgence in contagion could be possible as late as 2024.
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            Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England

            Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the capacity to generate variants with major genomic changes. The UK variant B.1.1.7 (also known as VOC 202012/01) has many mutations that alter virus attachment and entry into human cells. Using a variety of statistical and dynamic modeling approaches, Davies et al. characterized the spread of the B.1.1.7 variant in the United Kingdom. The authors found that the variant is 43 to 90% more transmissible than the predecessor lineage but saw no clear evidence for a change in disease severity, although enhanced transmission will lead to higher incidence and more hospital admissions. Large resurgences of the virus are likely to occur after the easing of control measures, and it may be necessary to greatly accelerate vaccine roll-out to control the epidemic. Science , this issue p. eabg3055 The major coronavirus variant that emerged at the end of 2020 in the UK is more transmissible than its predecessors and could spark resurgences. INTRODUCTION Several novel variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, emerged in late 2020. One of these, Variant of Concern (VOC) 202012/01 (lineage B.1.1.7), was first detected in southeast England in September 2020 and spread to become the dominant lineage in the United Kingdom in just a few months. B.1.1.7 has since spread to at least 114 countries worldwide. RATIONALE The rapid spread of VOC 202012/01 suggests that it transmits more efficiently from person to person than preexisting variants of SARS-CoV-2. This could lead to global surges in COVID-19 hospitalizations and deaths, so there is an urgent need to estimate how much more quickly VOC 202012/01 spreads, whether it is associated with greater or lesser severity of disease, and what control measures might be effective in mitigating its impact. We used social contact and mobility data, as well as demographic indicators linked to SARS-CoV-2 community testing data in England, to assess whether the spread of the new variant may be an artifact of higher baseline transmission rates in certain geographical areas or among specific demographic subpopulations. We then used a series of complementary statistical analyses and mathematical models to estimate the transmissibility of VOC 202012/01 across multiple datasets from the UK, Denmark, Switzerland, and the United States. Finally, we extended a mathematical model that has been extensively used to forecast COVID-19 dynamics in the UK to consider two competing SARS-CoV-2 lineages: VOC 202012/01 and preexisting variants. By fitting this model to a variety of data sources on infections, hospitalizations, and deaths across seven regions of England, we assessed different hypotheses for why the new variant appears to be spreading more quickly, estimated the severity of disease associated with the new variant, and evaluated control measures including vaccination and nonpharmaceutical interventions. Combining multiple lines of evidence allowed us to draw robust inferences. RESULTS The rapid spread of VOC 202012/01 is not an artifact of geographical differences in contact behavior and does not substantially differ by age, sex, or socioeconomic stratum. We estimate that the new variant has a 43 to 90% higher reproduction number (range of 95% credible intervals, 38 to 130%) than preexisting variants. Similar increases are observed in Denmark, Switzerland, and the United States. The most parsimonious explanation for this increase in the reproduction number is that people infected with VOC 202012/01 are more infectious than people infected with a preexisting variant, although there is also reasonable support for a longer infectious period and multiple mechanisms may be operating. Our estimates of severity are uncertain and are consistent with anything from a moderate decrease to a moderate increase in severity (e.g., 32% lower to 20% higher odds of death given infection). Nonetheless, our mathematical model, fitted to data up to 24 December 2020, predicted a large surge in COVID-19 cases and deaths in 2021, which has been borne out so far by the observed burden in England up to the end of March 2021. In the absence of stringent nonpharmaceutical interventions and an accelerated vaccine rollout, COVID-19 deaths in the first 6 months of 2021 were projected to exceed those in 2020 in England. CONCLUSION More than 98% of positive SARS-CoV-2 infections in England are now due to VOC 202012/01, and the spread of this new variant has led to a surge in COVID-19 cases and deaths. Other countries should prepare for potentially similar outcomes. Impact of SARS-CoV-2 Variant of Concern 202012/01. ( A ) Spread of VOC 202012/01 (lineage B.1.1.7) in England. ( B ) The estimated relative transmissibility of VOC 202012/01 (mean and 95% confidence interval) is similar across the United Kingdom as a whole, England, Denmark, Switzerland, and the United States. ( C ) Projected COVID-19 deaths (median and 95% confidence interval) in England, 15 December 2020 to 30 June 2021. Vaccine rollout and control measures help to mitigate the burden of VOC 202012/01. A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, VOC 202012/01 (lineage B.1.1.7), emerged in southeast England in September 2020 and is rapidly spreading toward fixation. Using a variety of statistical and dynamic modeling approaches, we estimate that this variant has a 43 to 90% (range of 95% credible intervals, 38 to 130%) higher reproduction number than preexisting variants. A fitted two-strain dynamic transmission model shows that VOC 202012/01 will lead to large resurgences of COVID-19 cases. Without stringent control measures, including limited closure of educational institutions and a greatly accelerated vaccine rollout, COVID-19 hospitalizations and deaths across England in the first 6 months of 2021 were projected to exceed those in 2020. VOC 202012/01 has spread globally and exhibits a similar transmission increase (59 to 74%) in Denmark, Switzerland, and the United States.
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              Potent neutralizing antibodies directed to multiple epitopes on SARS-CoV-2 spike

              The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic continues, with devasting consequences for human lives and the global economy1,2. The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this coronavirus. Here we report the isolation of sixty-one SARS-CoV-2-neutralizing monoclonal antibodies from five patients infected with SARS-CoV-2 and admitted to hospital with severe coronavirus disease 2019 (COVID-19). Among these are nineteen antibodies that potently neutralized authentic SARS-CoV-2 in vitro, nine of which exhibited very high potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng ml-1. Epitope mapping showed that this collection of nineteen antibodies was about equally divided between those directed against the receptor-binding domain (RBD) and those directed against the N-terminal domain (NTD), indicating that both of these regions at the top of the viral spike are immunogenic. In addition, two other powerful neutralizing antibodies recognized quaternary epitopes that overlap with the domains at the top of the spike. Cryo-electron microscopy reconstructions of one antibody that targets the RBD, a second that targets the NTD, and a third that bridges two separate RBDs showed that the antibodies recognize the closed, 'all RBD-down' conformation of the spike. Several of these monoclonal antibodies are promising candidates for clinical development as potential therapeutic and/or prophylactic agents against SARS-CoV-2.
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                Author and article information

                Contributors
                igor.rouzine@iephb.ru
                g.rozhnova@umcutrecht.nl
                Journal
                Commun Med (Lond)
                Commun Med (Lond)
                Communications Medicine
                Nature Publishing Group UK (London )
                2730-664X
                19 June 2023
                19 June 2023
                2023
                : 3
                : 86
                Affiliations
                [1 ]GRID grid.419730.8, ISNI 0000 0004 0440 2269, Immunogenetics, , Sechenov Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, ; Saint-Petersburg, Russia
                [2 ]GRID grid.5477.1, ISNI 0000000120346234, Julius Center for Health Sciences and Primary Care, , University Medical Center Utrecht, Utrecht University, ; Utrecht, The Netherlands
                [3 ]GRID grid.9983.b, ISNI 0000 0001 2181 4263, BioISI – Biosystems & Integrative Sciences Institute, Faculdade de Ciências, , Universidade de Lisboa, ; Lisboa, Portugal
                [4 ]GRID grid.5477.1, ISNI 0000000120346234, Center for Complex Systems Studies (CCSS), , Utrecht University, ; Utrecht, The Netherlands
                Author information
                http://orcid.org/0000-0002-0744-6705
                http://orcid.org/0000-0002-6725-7359
                Article
                320
                10.1038/s43856-023-00320-x
                10279745
                37336956
                dd763021-4d5e-4c93-97e9-3164c1cfe1fb
                © The Author(s) 2023

                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
                : 4 May 2022
                : 7 June 2023
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001826, ZonMw (Netherlands Organisation for Health Research and Development);
                Award ID: 10430362220002
                Award Recipient :
                Funded by: The European Union, VERDI project number 101045989. The Fundação para a Ciência e a Tecnologia, Portugal, project number 2022.01448.PTDC. ZonMw, The Netherlands, project number 10430362220002.
                Funded by: Federal Agency for Scientific Organizations (FASO Russia: topic no. AAAA-А18-118012290142-9).
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                © Springer Nature Limited 2023

                evolution,computational biology and bioinformatics,viral infection,public health

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