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      Lower vaccine-acquired immunity in the elderly population following two-dose BNT162b2 vaccination is alleviated by a third vaccine dose

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      1 , 2 , 3 , , 1 , 1 , 4 , 4 , 5 , 6 , 1 , 1 , 7 , 1 , 1 , 4 , 1 , 1 , 1 , 1 , 1 , 1 , 7 , 7 , 7 , 1 , 7 , 5 , 6 , 4 , 4 , 7 , 6 , 8 , 9 , 10 , 11 , 12 , SCOPE Cohort Study Group, 2 , 6 , 13 , 14 , 15 , 16 , 5 , 6 , 15 , 4 , 6 , 7 , 2 , 6 , 14 , 17 , 4 , 7 , 2 , 6 , 14 , 1 , 18 , 19 , 20
      Nature Communications
      Nature Publishing Group UK
      RNA vaccines, Viral infection, SARS-CoV-2, Immunological memory, Antibodies

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          Abstract

          Understanding the impact of age on vaccinations is essential for the design and delivery of vaccines against SARS-CoV-2. Here, we present findings from a comprehensive analysis of multiple compartments of the memory immune response in 312 individuals vaccinated with the BNT162b2 SARS-CoV-2 mRNA vaccine. Two vaccine doses induce high antibody and T cell responses in most individuals. However, antibody recognition of the Spike protein of the Delta and Omicron variants is less efficient than that of the ancestral Wuhan strain. Age-stratified analyses identify a group of low antibody responders where individuals ≥60 years are overrepresented. Waning of the antibody and cellular responses is observed in 30% of the vaccinees after 6 months. However, age does not influence the waning of these responses. Taken together, while individuals ≥60 years old take longer to acquire vaccine-induced immunity, they develop more sustained acquired immunity at 6 months post-vaccination. A third dose strongly boosts the low antibody responses in the older individuals against the ancestral Wuhan strain, Delta and Omicron variants.

          Abstract

          Responses to SARS-CoV-2 vaccines in different populations are important to define efficacy. Here the authors show using a cohort in Singapore that two doses of mRNA vaccine is less effective in recipients over 60 years of age and that a further dose of vaccine can improve these antibody levels.

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          Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

          Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. Results A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)
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            The trinity of COVID-19: immunity, inflammation and intervention

            Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the fundamental physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. Here, we provide an overview of the pathophysiology of SARS-CoV-2 infection. We describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression. From nascent reports describing SARS-CoV-2, we make inferences on the basis of the parallel pathophysiological and immunological features of the other human coronaviruses targeting the lower respiratory tract — severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Finally, we highlight the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation.
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              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.
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                Author and article information

                Contributors
                renia_laurent@idlabs.a-star.edu.sg
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                8 August 2022
                8 August 2022
                2022
                : 13
                : 4615
                Affiliations
                [1 ]GRID grid.185448.4, ISNI 0000 0004 0637 0221, A*STAR Infectious Diseases Labs (A*STAR ID Labs), Agency for Science, , Technology and Research (A*STAR), ; Singapore, Singapore
                [2 ]GRID grid.59025.3b, ISNI 0000 0001 2224 0361, Lee Kong Chian School of Medicine, , Nanyang Technological University, ; Singapore, Singapore
                [3 ]GRID grid.59025.3b, ISNI 0000 0001 2224 0361, School of Biological Sciences, , Nanyang Technological University, ; Singapore, Singapore
                [4 ]GRID grid.428397.3, ISNI 0000 0004 0385 0924, Programme in Emerging Infectious Diseases, , Duke-NUS Medical School, ; Singapore, Singapore
                [5 ]National Public Health Laboratory, Singapore, Singapore
                [6 ]GRID grid.508077.d, National Centre for Infectious Diseases, ; Singapore, Singapore
                [7 ]GRID grid.185448.4, ISNI 0000 0004 0637 0221, Singapore Immunology Network, Agency for Science, , Technology and Research (A*STAR), ; Singapore, Singapore
                [8 ]GRID grid.459815.4, ISNI 0000 0004 0493 0168, Ng Teng Fong General Hospital, ; Singapore, Singapore
                [9 ]GRID grid.413587.c, ISNI 0000 0004 0640 6829, Alexandra Hospital, ; Singapore, Singapore
                [10 ]GRID grid.412106.0, ISNI 0000 0004 0621 9599, Division of Infectious Diseases, Department of Medicine, , National University Hospital, National University Health System, ; Singapore, Singapore
                [11 ]GRID grid.466910.c, ISNI 0000 0004 0451 6215, National healthcare group polyclinic, ; Jurong, Singapore
                [12 ]GRID grid.4280.e, ISNI 0000 0001 2180 6431, National University Polyclinics, National University of Singapore, ; Singapore, Singapore
                [13 ]GRID grid.4280.e, ISNI 0000 0001 2180 6431, Saw Swee Hock School of Public Health, , National University of Singapore, ; Singapore, Singapore
                [14 ]GRID grid.240988.f, ISNI 0000 0001 0298 8161, Tan Tock Seng Hospital, ; Singapore, Singapore
                [15 ]GRID grid.4280.e, ISNI 0000 0001 2180 6431, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, , National University of Singapore, ; Singapore, Singapore
                [16 ]GRID grid.4280.e, ISNI 0000 0001 2180 6431, Life Sciences Institute, Centre for Life Sciences, , National University of Singapore, ; Singapore, Singapore
                [17 ]GRID grid.4280.e, ISNI 0000 0001 2180 6431, Department of Medicine, Yong Loo Lin School of Medicine, , National University of Singapore, ; Singapore, Singapore
                [18 ]GRID grid.4280.e, ISNI 0000 0001 2180 6431, Department of Biochemistry, Yong Loo Lin School of Medicine, , National University of Singapore, ; Singapore, Singapore
                [19 ]GRID grid.10025.36, ISNI 0000 0004 1936 8470, National Institute of Health Research, Health Protection Research Unit in Emerging and Zoonotic Infections, , University of Liverpool, ; Liverpool, UK
                [20 ]GRID grid.10025.36, ISNI 0000 0004 1936 8470, Institute of Infection, Veterinary and Ecological Sciences, , University of Liverpool, ; Liverpool, UK
                Author information
                http://orcid.org/0000-0002-8437-3204
                http://orcid.org/0000-0003-0502-2527
                http://orcid.org/0000-0001-7287-694X
                http://orcid.org/0000-0002-0003-541X
                http://orcid.org/0000-0002-7692-8265
                http://orcid.org/0000-0002-1763-913X
                http://orcid.org/0000-0002-8294-1474
                http://orcid.org/0000-0002-3112-7341
                http://orcid.org/0000-0001-5407-0280
                http://orcid.org/0000-0002-6110-7472
                http://orcid.org/0000-0002-9703-9096
                http://orcid.org/0000-0001-9170-2996
                http://orcid.org/0000-0003-4963-535X
                http://orcid.org/0000-0003-4978-5825
                http://orcid.org/0000-0001-6654-026X
                http://orcid.org/0000-0003-2752-0535
                http://orcid.org/0000-0003-1010-2230
                http://orcid.org/0000-0003-4071-5222
                Article
                32312
                10.1038/s41467-022-32312-1
                9358634
                35941158
                33065826-30dc-4538-900f-bc200c81db21
                © The Author(s) 2022

                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
                : 22 November 2021
                : 23 July 2022
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001348, Agency for Science, Technology and Research (A*STAR);
                Award ID: SC3521-901700
                Award ID: ACCL/19-GAP064-R20H-H
                Award ID: H/20/04/g1/006
                Award ID: #SC3521-901700
                Award ID: #SC3521-901700
                Award ID: ACCL/19-GAP064-R20H-H
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100001349, MOH | National Medical Research Council (NMRC);
                Award ID: COVID19RF-001
                Award ID: COVID19RF-007
                Award ID: COVID19RF-0008
                Award ID: COVID19RF-011
                Award ID: COVID19RF-060
                Award ID: COVID19RF-007
                Award ID: COVID19RF-007
                Award ID: COVID19RF-001
                Award ID: COVID19RF-060)
                Award ID: COVID19RF-001
                Award ID: COVID19RF-011
                Award ID: COVID19RF-060
                Award ID: COVID19RF-060
                Award ID: COVID19RF-001
                Award ID: COVID19RF-0008
                Award ID: COVID19RF-060
                Award ID: COVID19RF-011
                Award ID: COVID19RF-060
                Award ID: COVID19RF-007
                Award ID: COVID19RF-0008
                Award ID: COVID19RF-011
                Award ID: COVID19RF-060
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100001471, A*STAR | Singapore Institute of Manufacturing Technology (Singapore Institute of Manufacturing Technology - A STAR);
                Award ID: H/20/04/g1/006
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2022

                Uncategorized
                rna vaccines,viral infection,sars-cov-2,immunological memory,antibodies
                Uncategorized
                rna vaccines, viral infection, sars-cov-2, immunological memory, antibodies

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