Longitudinal Isolation of Potent Near-Germline SARS-CoV-2-Neutralizing Antibodies from COVID-19 Patients

Kreer, Christoph; Zehner, Matthias; Weber, Timm; Ercanoglu, Meryem S.; Gieselmann, Lutz; Rohde, Cornelius; Halwe, Sandro; Korenkov, Michael; Schommers, Philipp; Vanshylla, Kanika; Cristanziano, Veronica Di; Janicki, Hanna; Brinker, Reinhild; Ashurov, Artem; Krähling, Verena; Kupke, Alexandra; Cohen-Dvashi, Hadas; Koch, Manuel; Eckert, Jan Mathis; Lederer, Simone; Pfeifer, Nico; Wolf, Timo; Vehreschild, Maria J.G.T.; Wendtner, Clemens; Diskin, Ron; Gruell, Henning; Becker, Stephan; Klein, Florian

doi:10.1016/j.cell.2020.08.046

Cited by 131 publications

(188 citation statements)

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“…However, few of these antibodies were neutralising, in agreement with other results [143,144]. RBD-specific antibodies were also shown to have potent neutralising activity in a range of other small studies [112,143,[145][146][147][148][149][150][151], including one using an IgA isotype [152]. Neutralising ability correlated in particular with competition for the angiotensin converting enzyme-2 (ACE2) receptor [112,114,145].…”

Section: Protective Immunitysupporting

confidence: 85%

“…Neutralising ability correlated in particular with competition for the angiotensin converting enzyme-2 (ACE2) receptor [112,114,145]. Two studies demonstrated a lack of association with affinity [115,145], although a moderate correlation with binding affinity was reported in one study [146]. Potently neutralising N specific antibodies were isolated in other studies [115,148], and the potential for antibodies binding to protease cleavage sites as alternatives to RBD isolated from convalescent plasma has also been identified [153], suggesting an important role in preventing antibody dependent enhancement of viral entry.…”

Section: Protective Immunitymentioning

confidence: 96%

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Antibody response to SARS-CoV-2 infection in humans: A systematic review

et al. 2020

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Background Progress in characterising the humoral immune response to Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) has been rapid but areas of uncertainty persist. Assessment of the full range of evidence generated to date to understand the characteristics of the antibody response, its dynamics over time, its determinants and the immunity it confers will have a range of clinical and policy implications for this novel pathogen. This review comprehensively evaluated evidence describing the antibody response to SARS-CoV-2 published from 01/01/2020-26/06/2020. Methods Systematic review. Keyword-structured searches were carried out in MEDLINE, Embase and COVID-19 Primer. Articles were independently screened on title, abstract and full text by two researchers, with arbitration of disagreements. Data were double-extracted into a pre-designed template, and studies critically appraised using a modified version of the Public Health Ontario Meta-tool for Quality Appraisal of Public Health Evidence (MetaQAT) tool, with resolution of disagreements by consensus. Findings were narratively synthesised. Results 150 papers were included. Most studies (113 or 75%) were observational in design, were based wholly or primarily on data from hospitalised patients (108, 72%) and had important methodological limitations. Few considered mild or asymptomatic infection. Antibody dynamics were well described in the acute phase, up to around three months from disease onset, but the picture regarding correlates of the antibody response was inconsistent. IgM was consistently detected before IgG in included studies, peaking at weeks two to five and declining over a further three to five weeks post-symptom onset depending on the patient group; IgG peaked around weeks three to seven post-symptom onset then plateaued, generally persisting for at least eight weeks. Neutralising antibodies were detectable within seven to 15 days following disease onset, with levels increasing until days 14–22 before levelling and then decreasing, but titres were lower in those with asymptomatic or clinically mild disease. Specific and potent neutralising antibodies have been isolated from convalescent plasma. Cross-reactivity but limited cross-neutralisation with other human coronaviridae was reported. Evidence for protective immunity in vivo was limited to small, short-term animal studies, showing promising initial results in the immediate recovery phase. Conclusions Literature on antibody responses to SARS-CoV-2 is of variable quality with considerable heterogeneity of methods, study participants, outcomes measured and assays used. Although acute phase antibody dynamics are well described, longer-term patterns are much less well evidenced. Comprehensive assessment of the role of demographic characteristics and disease severity on antibody responses is needed. Initial findings of low neutralising antibody titres and possible waning of titres over time may have implications for sero-surveillance and disease control policy, although further evidence is needed. The detection of potent neutralising antibodies in convalescent plasma is important in the context of development of therapeutics and vaccines. Due to limitations with the existing evidence base, large, cross-national cohort studies using appropriate statistical analysis and standardised serological assays and clinical classifications should be prioritised.

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Section: Protective Immunitysupporting

confidence: 85%

Section: Protective Immunitymentioning

confidence: 96%

Antibody response to SARS-CoV-2 infection in humans: A systematic review

et al. 2020

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“…Convalescent plasma has been used to treat many patients with severe COVID-19 illness, which has been safe and reported to reduce mortality, although no data are available from randomized, clinical trials 7,8 . Analysis of SARS-CoV2 speci c NAbs from infected individuals showed that the majority of such antibodies target the receptor binding domain (RBD) and prevent binding to the host cell receptor ACE2 9 . However, there have been recent concerns regarding decline of both total antibodies and NAbs to SARS-CoV-2 at 8 weeks since onset of illness, especially in those with mild illness 10 .…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 neutralizing antibodies in patients with varying severity of acute COVID-19 illness

Jeewandara

Jayathilaka

Gomes

et al. 2020

Preprint

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In order to support vaccine development, and to aid convalescent plasma therapy, it would be important to understand the kinetics, timing and persistence of SARS-CoV2 neutralizing antibodies (NAbs), and their association with clinical disease severity. Therefore, we used a surrogate viral neutralization test to evaluate their levels in patients with varying severity of illness, in those with prolonged shedding and those with mild/asymptomatic illness at various time points.Patients with severe or moderate COVID-19 illness had earlier appearance of NAbs at higher levels compared to those with mild or asymptomatic illness. Furthermore, those who had prolonged shedding of the virus, had NAbs appearing faster and at higher levels than those who cleared the virus earlier. During the first week of illness the NAb levels of those with mild illness was significantly less (p=0.01), compared to those with moderate and severe illness. At the end of 4 weeks (28 days), although 89% had Nabs, 38/76 (50%) in those with >90 days had a negative result for the presence of NAbs. The Ab levels significantly declined during convalescence (>90 days since onset of illness), compared to 4 to 8 weeks since onset of illness. Our data show that high levels of NAbs during early illness associated with clinical disease severity and that these antibodies declined in 50% of individuals after 3 months since onset of illness.

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“…Thus, how to precisely regulate virus-induced dysfunctional complement activation in COVID-19 patients remains to be elucidated. The SARS-CoV-2 N protein is a highly immunopathogenic viral protein that elicits high titers of binding antibodies in humoral immune responses [22][23][24] . Several studies have reported the isolation of human monoclonal antibodies (mAbs) targeting the SARS-CoV-2 spike (S) protein, helping explain the possible developing therapeutic interventions for COVID-19 22,[25][26][27][28][29] .…”

Section: Mainmentioning

confidence: 99%

A COVID-19 antibody curbs SARS-CoV-2 nucleocapsid protein-induced complement hyperactivation

Kang

Yang

et al. 2020

Preprint

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Although human antibodies elicited by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein are profoundly boosted upon infection, little is known about the function of N-reactive antibodies. Herein, we isolated and profiled a panel of 32 N protein-specific monoclonal antibodies (mAbs) from a quick recovery coronavirus disease-19 (COVID-19) convalescent patient who had dominant antibody responses to the SARS-CoV-2 N protein rather than to the SARS-CoV-2 spike (S) protein. The complex structure of the N protein RNA binding domain with the mAb with the highest binding affinity (nCoV396) revealed changes in the epitopes and antigen’s allosteric regulation. Functionally, a virus-free complement hyper-activation analysis demonstrated that nCoV396 specifically compromises the N protein-induced complement hyper-activation, which is a risk factor for the morbidity and mortality of COVID-19 patients, thus laying the foundation for the identification of functional anti-N protein mAbs.

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Longitudinal Isolation of Potent Near-Germline SARS-CoV-2-Neutralizing Antibodies from COVID-19 Patients

Cited by 131 publications

References 0 publications

Antibody response to SARS-CoV-2 infection in humans: A systematic review

Antibody response to SARS-CoV-2 infection in humans: A systematic review

SARS-CoV-2 neutralizing antibodies in patients with varying severity of acute COVID-19 illness

A COVID-19 antibody curbs SARS-CoV-2 nucleocapsid protein-induced complement hyperactivation

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