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1.
Immunity ; 2022.
Article in English | ScienceDirect | ID: covidwho-1778211

ABSTRACT

Summary The SARS-CoV-2 Omicron variant can escape neutralization by vaccine-elicited and convalescent antibodies. Memory B cells (MBCs) represent another layer of protection against SARS-CoV-2, as they persist after infection and vaccination and improve their affinity. Whether MBCs elicited by mRNA vaccines can recognize Omicron variant remains unclear. We assessed affinity and neutralization potency against the Omicron variant of several hundred naturally expressed MBC-derived monoclonal IgG antibodies from vaccinated COVID-19-recovered and -naïve individuals. Compared to other variants of concern, Omicron evaded recognition of a larger proportion of MBC-derived antibodies, with only 30% retaining high affinity against the Omicron-RBD, and the reduction in neutralization potency was even more pronounced. Nonetheless, neutralizing MBC clones could be found in all individuals analysed. Therefore, despite the strong immune escape potential of the Omicron variant, these results suggest that the MBC repertoire generated by mRNA vaccines still provide some protection against the Omicron variant in vaccinated individuals.

2.
J Infect Dis ; 224(9): 1489-1499, 2021 11 16.
Article in English | MEDLINE | ID: covidwho-1522216

ABSTRACT

BACKGROUND: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a complex antibody response that varies by orders of magnitude between individuals and over time. METHODS: We developed a multiplex serological test for measuring antibodies to 5 SARS-CoV-2 antigens and the spike proteins of seasonal coronaviruses. We measured antibody responses in cohorts of hospitalized patients and healthcare workers followed for up to 11 months after symptoms. A mathematical model of antibody kinetics was used to quantify the duration of antibody responses. Antibody response data were used to train algorithms for estimating time since infection. RESULTS: One year after symptoms, we estimate that 36% (95% range, 11%-94%) of anti-Spike immunoglobulin G (IgG) remains, 31% (95% range, 9%-89%) anti-RBD IgG remains, and 7% (1%-31%) of anti-nucleocapsid IgG remains. The multiplex assay classified previous infections into time intervals of 0-3 months, 3-6 months, and 6-12 months. This method was validated using data from a seroprevalence survey in France, demonstrating that historical SARS-CoV-2 transmission can be reconstructed using samples from a single survey. CONCLUSIONS: In addition to diagnosing previous SARS-CoV-2 infection, multiplex serological assays can estimate the time since infection, which can be used to reconstruct past epidemics.


Subject(s)
Antibodies, Viral/blood , COVID-19/blood , COVID-19/immunology , Serologic Tests/methods , Adolescent , Adult , Aged , Aged, 80 and over , Antibody Formation , Antibody Specificity , COVID-19/epidemiology , Female , France/epidemiology , Humans , Immunoglobulin G/blood , Kinetics , Male , Middle Aged , SARS-CoV-2/immunology , Sensitivity and Specificity , Seroepidemiologic Studies , Young Adult
3.
Transfusion Clinique et Biologique ; 28(4):S46-S46, 2021.
Article in French | Academic Search Complete | ID: covidwho-1492680

ABSTRACT

L'émergence de variants portant des mutations dans des épitopes clés a fait craindre que l'évolution virale n'érode l'immunité acquise. Caractérisé la dynamique et la fonctionnalité de la réponse B mémoire naturelle et acquise après administration d'un vaccin à ARNm. Nous avons analysé, au cours du temps, 33 sujets avec un antécédent de la COVID-19 et 23 individus naïfs avant et après vaccination par ARNm. Nous avons combiné différentes approches, l'analyse transcriptomique en cellule unique, le séquençage du VH, le phénotypages cellulaire par cytométrie en flux multi-paramétriques ainsi que la mesure du pouvoir neutralisant des anticorps et leur affinité. La mémoire B anti-SARS-Cov-2 porte une empreinte d'un passage par le centre germinatif et parait stable chez la majorité des patients, et ce un an après l'infection initiale. Le rappel vaccinal mobilise les B mémoires sans entraîner de réduction de leur diversité. Chez les patients guéris, les B mémoires spécifiques du RBD montrent des preuves évidentes de sélection par affinité, un processus toujours en cours chez les individus naïfs, deux mois après leur deuxième dose. Seule une faible proportion de clones B mémoires spécifiques du domaine RBD n'a pas réussi à reconnaître le variant B.1.351. Néanmoins, de puissantes B mémoires neutralisant le B.1.351 pourraient toujours être détectés chez tous les individus naïfs et guéris de la Covid-19. En raison de sa diversité et de son affinité, le répertoire B mémoires anti la protéine RBDwt, sélectionné lors de l'infection ou la vaccination contient des clones capables de faire face à l'évolution virale. (French) [ABSTRACT FROM AUTHOR] Copyright of Transfusion Clinique et Biologique is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

4.
Immunity ; 54(12): 2893-2907.e5, 2021 12 14.
Article in English | MEDLINE | ID: covidwho-1433403

ABSTRACT

In addition to serum immunoglobulins, memory B cell (MBC) generation against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is another layer of immune protection, but the quality of MBC responses in naive and coronavirus disease 2019 (COVID-19)-recovered individuals after vaccination remains ill defined. We studied longitudinal cohorts of naive and disease-recovered individuals for up to 2 months after SARS-CoV-2 mRNA vaccination. We assessed the quality of the memory response by analysis of antibody repertoires, affinity, and neutralization against variants of concern (VOCs) using unbiased cultures of 2,452 MBCs. Upon boosting, the MBC pool of recovered individuals expanded selectively, matured further, and harbored potent neutralizers against VOCs. Although naive individuals had weaker neutralizing serum responses, half of their RBD-specific MBCs displayed high affinity toward multiple VOCs, including delta (B.1.617.2), and one-third retained neutralizing potency against beta (B.1.351). Our data suggest that an additional challenge in naive vaccinees could recall such affinity-matured MBCs and allow them to respond efficiently to VOCs.


Subject(s)
/immunology , COVID-19/immunology , Precursor Cells, B-Lymphoid/immunology , RNA, Messenger/genetics , SARS-CoV-2/physiology , Animals , Antibodies, Neutralizing/metabolism , Antibodies, Viral/metabolism , Antibody Affinity , Cells, Cultured , Convalescence , Humans , Immunization, Secondary , Immunologic Memory , Mass Vaccination , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology
5.
J Infect Dis ; 224(9): 1489-1499, 2021 11 16.
Article in English | MEDLINE | ID: covidwho-1317919

ABSTRACT

BACKGROUND: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a complex antibody response that varies by orders of magnitude between individuals and over time. METHODS: We developed a multiplex serological test for measuring antibodies to 5 SARS-CoV-2 antigens and the spike proteins of seasonal coronaviruses. We measured antibody responses in cohorts of hospitalized patients and healthcare workers followed for up to 11 months after symptoms. A mathematical model of antibody kinetics was used to quantify the duration of antibody responses. Antibody response data were used to train algorithms for estimating time since infection. RESULTS: One year after symptoms, we estimate that 36% (95% range, 11%-94%) of anti-Spike immunoglobulin G (IgG) remains, 31% (95% range, 9%-89%) anti-RBD IgG remains, and 7% (1%-31%) of anti-nucleocapsid IgG remains. The multiplex assay classified previous infections into time intervals of 0-3 months, 3-6 months, and 6-12 months. This method was validated using data from a seroprevalence survey in France, demonstrating that historical SARS-CoV-2 transmission can be reconstructed using samples from a single survey. CONCLUSIONS: In addition to diagnosing previous SARS-CoV-2 infection, multiplex serological assays can estimate the time since infection, which can be used to reconstruct past epidemics.


Subject(s)
Antibodies, Viral/blood , COVID-19/blood , COVID-19/immunology , Serologic Tests/methods , Adolescent , Adult , Aged , Aged, 80 and over , Antibody Formation , Antibody Specificity , COVID-19/epidemiology , Female , France/epidemiology , Humans , Immunoglobulin G/blood , Kinetics , Male , Middle Aged , SARS-CoV-2/immunology , Sensitivity and Specificity , Seroepidemiologic Studies , Young Adult
6.
Lancet Microbe ; 2(2): e60-e69, 2021 02.
Article in English | MEDLINE | ID: covidwho-1065710

ABSTRACT

BACKGROUND: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces an antibody response targeting multiple antigens that changes over time. This study aims to take advantage of this complexity to develop more accurate serological diagnostics. METHODS: A multiplex serological assay was developed to measure IgG and IgM antibody responses to seven SARS-CoV-2 spike or nucleoprotein antigens, two antigens for the nucleoproteins of the 229E and NL63 seasonal coronaviruses, and three non-coronavirus antigens. Antibodies were measured in serum samples collected up to 39 days after symptom onset from 215 adults in four French hospitals (53 patients and 162 health-care workers) with quantitative RT-PCR-confirmed SARS-CoV-2 infection, and negative control serum samples collected from healthy adult blood donors before the start of the SARS-CoV-2 epidemic (335 samples from France, Thailand, and Peru). Machine learning classifiers were trained with the multiplex data to classify individuals with previous SARS-CoV-2 infection, with the best classification performance displayed by a random forests algorithm. A Bayesian mathematical model of antibody kinetics informed by prior information from other coronaviruses was used to estimate time-varying antibody responses and assess the sensitivity and classification performance of serological diagnostics during the first year following symptom onset. A statistical estimator is presented that can provide estimates of seroprevalence in very low-transmission settings. FINDINGS: IgG antibody responses to trimeric spike protein (Stri) identified individuals with previous SARS-CoV-2 infection with 91·6% (95% CI 87·5-94·5) sensitivity and 99·1% (97·4-99·7) specificity. Using a serological signature of IgG and IgM to multiple antigens, it was possible to identify infected individuals with 98·8% (96·5-99·6) sensitivity and 99·3% (97·6-99·8) specificity. Informed by existing data from other coronaviruses, we estimate that 1 year after infection, a monoplex assay with optimal anti-Stri IgG cutoff has 88·7% (95% credible interval 63·4-97·4) sensitivity and that a four-antigen multiplex assay can increase sensitivity to 96·4% (80·9-100·0). When applied to population-level serological surveys, statistical analysis of multiplex data allows estimation of seroprevalence levels less than 2%, below the false-positivity rate of many other assays. INTERPRETATION: Serological signatures based on antibody responses to multiple antigens can provide accurate and robust serological classification of individuals with previous SARS-CoV-2 infection. This provides potential solutions to two pressing challenges for SARS-CoV-2 serological surveillance: classifying individuals who were infected more than 6 months ago and measuring seroprevalence in serological surveys in very low-transmission settings. FUNDING: European Research Council. Fondation pour la Recherche Médicale. Institut Pasteur Task Force COVID-19.


Subject(s)
COVID-19 , Adult , Antibodies, Viral , Bayes Theorem , COVID-19/diagnosis , Humans , Immunoglobulin G , Immunoglobulin M , Machine Learning , SARS-CoV-2 , Sensitivity and Specificity , Seroepidemiologic Studies
7.
Cell ; 184(5): 1201-1213.e14, 2021 03 04.
Article in English | MEDLINE | ID: covidwho-1062272

ABSTRACT

Memory B cells play a fundamental role in host defenses against viruses, but to date, their role has been relatively unsettled in the context of SARS-CoV-2. We report here a longitudinal single-cell and repertoire profiling of the B cell response up to 6 months in mild and severe COVID-19 patients. Distinct SARS-CoV-2 spike-specific activated B cell clones fueled an early antibody-secreting cell burst as well as a durable synchronous germinal center response. While highly mutated memory B cells, including pre-existing cross-reactive seasonal Betacoronavirus-specific clones, were recruited early in the response, neutralizing SARS-CoV-2 RBD-specific clones accumulated with time and largely contributed to the late, remarkably stable, memory B cell pool. Highlighting germinal center maturation, these cells displayed clear accumulation of somatic mutations in their variable region genes over time. Overall, these findings demonstrate that an antigen-driven activation persisted and matured up to 6 months after SARS-CoV-2 infection and may provide long-term protection.


Subject(s)
B-Lymphocytes/immunology , COVID-19/immunology , Immunologic Memory , Adult , COVID-19/physiopathology , Flow Cytometry , Germinal Center/cytology , Humans , Lymphocyte Activation , Middle Aged , Severity of Illness Index , Single-Cell Analysis , Spike Glycoprotein, Coronavirus/chemistry
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