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      Quantifying neutralising antibody responses against SARS-CoV-2 in dried blood spots (DBS) and paired sera

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          Abstract

          The ongoing SARS-CoV-2 pandemic was initially managed by non-pharmaceutical interventions such as diagnostic testing, isolation of positive cases, physical distancing and lockdowns. The advent of vaccines has provided crucial protection against SARS-CoV-2. Neutralising antibody (nAb) responses are a key correlate of protection, and therefore measuring nAb responses is essential for monitoring vaccine efficacy. Fingerstick dried blood spots (DBS) are ideal for use in large-scale sero-surveillance because they are inexpensive, offer the option of self-collection and can be transported and stored at ambient temperatures. Such advantages also make DBS appealing to use in resource-limited settings and in potential future pandemics. In this study, nAb responses in sera, venous blood and fingerstick blood stored on filter paper were measured. Samples were collected from SARS-CoV-2 acutely infected individuals, SARS-CoV-2 convalescent individuals and SARS-CoV-2 vaccinated individuals. Good agreement was observed between the nAb responses measured in eluted DBS and paired sera. Stability of nAb responses was also observed in sera stored on filter paper at room temperature for 28 days. Overall, this study provides support for the use of filter paper as a viable sample collection method to study nAb responses.

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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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            Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

            Abstract Background Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. Methods This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. Results The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups. Conclusions The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.)
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              STATISTICAL METHODS FOR ASSESSING AGREEMENT BETWEEN TWO METHODS OF CLINICAL MEASUREMENT

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                Author and article information

                Contributors
                g.pollakis@liverpool.ac.uk
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                11 September 2023
                11 September 2023
                2023
                : 13
                : 15014
                Affiliations
                [1 ]GRID grid.10025.36, ISNI 0000 0004 1936 8470, Department of Clinical Infection, Microbiology and Immunology (CIMI), Institute of Infection, Veterinary and Ecological Sciences (IVES), , University of Liverpool, ; Liverpool, L69 7BE UK
                [2 ]GRID grid.10025.36, ISNI 0000 0004 1936 8470, Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology (ISMIB), , University of Liverpool, ; Liverpool, L69 3BX UK
                [3 ]GRID grid.301713.7, ISNI 0000 0004 0393 3981, MRC-University of Glasgow Centre for Virus Research, ; 464 Bearsden Road, Glasgow, G61 1QH UK
                [4 ]GRID grid.10025.36, ISNI 0000 0004 1936 8470, Faculty of Health and Life Sciences, Institute of Infection, Veterinary and Ecological Sciences, , University of Liverpool, ; Liverpool, UK
                [5 ]GRID grid.271308.f, ISNI 0000 0004 5909 016X, Antimicrobial Resistance and Hospital Acquired Infection Department, , Public Health England, ; London, UK
                [6 ]GRID grid.271308.f, ISNI 0000 0004 5909 016X, Blood Borne Virus Unit, Virus Reference Department, National Infection Service, , Public Health England, ; London, UK
                [7 ]GRID grid.13097.3c, ISNI 0000 0001 2322 6764, Department of Infectious Diseases, Centre for Clinical Infection and Diagnostics Research, School of Immunology and Microbial Sciences, , King’s College London, ; London, UK
                [8 ]GRID grid.5379.8, ISNI 0000000121662407, Division of Informatics, Imaging and Data Science, Faculty of Biology, Medicine and Health, Centre for Health Informatics, School of Health Sciences, Manchester Academic Health Science Centre, , University of Manchester, ; Manchester, UK
                [9 ]GRID grid.4305.2, ISNI 0000 0004 1936 7988, Centre for Medical Informatics, The Usher Institute, , University of Edinburgh, ; Edinburgh, UK
                [10 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Nuffield Department of Medicine, Centre for Tropical Medicine and Global Health, , University of Oxford, ; Old Road Campus, Roosevelt Drive, Oxford, UK
                [11 ]GRID grid.4305.2, ISNI 0000 0004 1936 7988, Department of Child Life and Health, , University of Edinburgh, ; Edinburgh, UK
                [12 ]GRID grid.7445.2, ISNI 0000 0001 2113 8111, Department of Epidemiology and Biostatistics, Faculty of Medicine, School of Public Health, , Imperial College London, ; London, UK
                [13 ]GRID grid.11835.3e, ISNI 0000 0004 1936 9262, Department of Infection, Immunity and Cardiovascular Disease, , University of Sheffield, ; Sheffield, UK
                [14 ]GRID grid.7445.2, ISNI 0000 0001 2113 8111, Department of Infectious Disease, , Imperial College London, ; London, UK
                [15 ]GRID grid.5335.0, ISNI 0000000121885934, Department of Medicine, , University of Cambridge, ; Cambridge, Cambridgeshire UK
                [16 ]GRID grid.10025.36, ISNI 0000 0004 1936 8470, Department of Molecular and Clinical Cancer Medicine, , University of Liverpool, ; Liverpool, UK
                [17 ]GRID grid.7445.2, ISNI 0000 0001 2113 8111, Department of Pediatrics and Virology, St Mary’s Medical School Bldg, , Imperial College London, ; London, UK
                [18 ]GRID grid.10025.36, ISNI 0000 0004 1936 8470, Department of Pharmacology, , University of Liverpool, ; Liverpool, UK
                [19 ]GRID grid.83440.3b, ISNI 0000000121901201, Division of Infection and Immunity, , University College London, ; London, UK
                [20 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Division of Structural Biology, The Wellcome Centre for Human Genetics, , University of Oxford, ; Headington, Oxford, OX3 7BN UK
                [21 ]GRID grid.4305.2, ISNI 0000 0004 1936 7988, EPCC, , University of Edinburgh, ; Edinburgh, UK
                [22 ]GRID grid.83440.3b, ISNI 0000000121901201, Institute for Global Health, , University College London, ; London, UK
                [23 ]GRID grid.4305.2, ISNI 0000 0004 1936 7988, Institute of Evolutionary Biology, , University of Edinburgh, ; Edinburgh, UK
                [24 ]GRID grid.6572.6, ISNI 0000 0004 1936 7486, Institute of Microbiology and Infection, , University of Birmingham, ; Birmingham, UK
                [25 ]GRID grid.10025.36, ISNI 0000 0004 1936 8470, Institute of Translational Medicine, , University of Liverpool, ; Liverpool, Merseyside UK
                [26 ]GRID grid.418716.d, ISNI 0000 0001 0709 1919, Intensive Care Unit, , Royal Infirmary Edinburgh, ; Edinburgh, UK
                [27 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Nuffield Department of Medicine, ISARIC Global Support Centre, Centre for Tropical Medicine and Global Health, , University of Oxford, ; Oxford, UK
                [28 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, ISARIC, Global Support Centre, COVID-19 Clinical Research Resources, Epidemic Diseases Research Group, Oxford (ERGO), , University of Oxford, ; Oxford, UK
                [29 ]GRID grid.10025.36, ISNI 0000 0004 1936 8470, Liverpool Clinical Trials Centre, , University of Liverpool, ; Liverpool, UK
                [30 ]GRID grid.48004.38, ISNI 0000 0004 1936 9764, Liverpool School of Tropical Medicine, ; Liverpool, UK
                [31 ]GRID grid.10025.36, ISNI 0000 0004 1936 8470, Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, , University of Liverpool, ; Liverpool, UK
                [32 ]GRID grid.4305.2, ISNI 0000 0004 1936 7988, MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, , University of Edinburgh, ; Edinburgh, UK
                [33 ]GRID grid.7445.2, ISNI 0000 0001 2113 8111, National Heart and Lung Institute, , Imperial College London, ; London, UK
                [34 ]GRID grid.271308.f, ISNI 0000 0004 5909 016X, National Infection Service, , Public Health England, ; London, UK
                [35 ]GRID grid.7445.2, ISNI 0000 0001 2113 8111, Department of Metabolism, Digestion and Reproduction, National Phenome Centre, , Imperial College London, ; London, W12 0NN UK
                [36 ]GRID grid.240404.6, ISNI 0000 0001 0440 1889, Nottingham University Hospitals NHS Trust, ; Nottingham, UK
                [37 ]GRID grid.8348.7, ISNI 0000 0001 2306 7492, Nuffield Department of Medicine, , John Radcliffe Hospital, ; Oxford, UK
                [38 ]GRID grid.46699.34, ISNI 0000 0004 0391 9020, Paediatric Liver, GI & Nutrition Centre and MowatLabs, , King’s College Hospital, ; London, UK
                [39 ]GRID grid.508718.3, Public Health Scotland, ; Edinburgh, UK
                [40 ]GRID grid.4305.2, ISNI 0000 0004 1936 7988, Roslin Institute, , University of Edinburgh, ; Easter Bush, Edinburgh, EH25 9RG UK
                [41 ]GRID grid.4305.2, ISNI 0000 0004 1936 7988, School of Informatics, , University of Edinburgh, ; Edinburgh, UK
                [42 ]Section of Biomolecular Medicine, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Sir Alexander Fleming Building, Exhibition Rd, London, SW7 2AZ UK
                [43 ]GRID grid.11835.3e, ISNI 0000 0004 1936 9262, Department of Infection, Immunity and Cardiovascular Disease, The Florey Institute for Host-Pathogen Interactions, , University of Sheffield, ; Sheffield, UK
                [44 ]GRID grid.4305.2, ISNI 0000 0004 1936 7988, The Roslin Institute, , University of Edinburgh, ; Edinburgh, UK
                [45 ]GRID grid.271308.f, ISNI 0000 0004 5909 016X, Virology Reference Department, National Infection Service, , Public Health England, ; Colindale Avenue, London, UK
                [46 ]GRID grid.508061.a, ISNI 0000 0004 9128 2882, NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, ; Liverpool, UK
                [47 ]GRID grid.10025.36, ISNI 0000 0004 1936 8470, Respiratory Medicine, Alder Hey Children’s Hospital, Institute in The Park, , University of Liverpool, ; Liverpool, UK
                [48 ]GRID grid.416928.0, ISNI 0000 0004 0496 3293, Walton Centre NHS Foundation Trust, ; Liverpool, UK
                [49 ]GRID grid.415970.e, ISNI 0000 0004 0417 2395, Tropical and Infectious Disease Unit, , Royal Liverpool University Hospital, ; Liverpool, UK
                [50 ]GRID grid.511123.5, ISNI 0000 0004 5988 7216, Department of Infectious Diseases, , Queen Elizabeth University Hospital, ; Glasgow, UK
                [51 ]GRID grid.413301.4, ISNI 0000 0001 0523 9342, NHS Greater Glasgow and Clyde, ; Glasgow, UK
                [52 ]GRID grid.436365.1, ISNI 0000 0000 8685 6563, Transfusion Microbiology, , National Health Service Blood and Transplant, ; London, UK
                [53 ]GRID grid.420545.2, ISNI 0000 0004 0489 3985, Department of Infectious Diseases, , Guy’s and St Thomas’ NHS Foundation Trust, ; London, UK
                [54 ]GRID grid.7445.2, ISNI 0000 0001 2113 8111, MRC Centre for Molecular Bacteriology and Infection, , Imperial College London, ; London, UK
                [55 ]GRID grid.418624.d, ISNI 0000 0004 0614 6369, Clatterbridge Cancer Centre NHS Foundation Trust, ; Liverpool, L7 8YA UK
                [56 ]GRID grid.417895.6, ISNI 0000 0001 0693 2181, Imperial College Healthcare NHS Trust: London, ; London, UK
                [57 ]GRID grid.7445.2, ISNI 0000 0001 2113 8111, Section of Bioanalytical Chemistry, Department of Metabolism, Digestion and Reproduction, , Imperial College London, ; London, SW7 2AZ UK
                [58 ]GRID grid.410556.3, ISNI 0000 0001 0440 1440, Department of Microbiology/Infectious Diseases, John Radcliffe Hospital, , Oxford University Hospitals NHS Foundation Trust, ; Oxford, UK
                [59 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Translational Gastroenterology Unit, Nuffield Department of Medicine, , University of Oxford, ; Oxford, UK
                [60 ]GRID grid.13097.3c, ISNI 0000 0001 2322 6764, Institute of Liver Studies, , King’s College London, ; London, UK
                [61 ]GRID grid.7445.2, ISNI 0000 0001 2113 8111, Section of Genomic and Environmental Medicine, Respiratory Division, , National Heart and Lung Institute, ; Guy Scadding Building, Dovehouse St., London, SW3 3LY UK
                Article
                41928
                10.1038/s41598-023-41928-2
                10495436
                37697014
                942f18cd-7d7b-47c5-8ba1-228af7d97bd7
                © Springer Nature Limited 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 13 April 2023
                : 4 September 2023
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100000836, University of Liverpool;
                Funded by: Saudi Arabian Government
                Funded by: National Institute for Health and Care Research
                Award ID: CO-CIN-01
                Funded by: Wellcome Trust PhD studentship
                Award ID: 102172/B/13/Z
                Award Recipient :
                Funded by: NIHR and UK Research and Innovation
                Award ID: CV220-169
                Award ID: MC_PC_19059
                Award ID: CO-CIN-01
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                © Springer Nature Limited 2023

                Uncategorized
                infectious diseases,immunology,microbiology
                Uncategorized
                infectious diseases, immunology, microbiology

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