Neutralizing Antibodies Against SARS-CoV-2—Important Questions, Unclear Answers

Katz, Mitchell H.

doi:10.1001/jamainternmed.2020.4624

Cited by 9 publications

(6 citation statements)

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“…The observed waning nAb does not mean that individuals lose their immune status or are susceptible to future re‐infections; only their level is below the defined cut‐off for donation. Even if nAb becomes undetectable in the future, it is likely that in re‐exposure, both the memory and killer T cells will be engaged in secondary immunologic response 32,45 . It is possible that CCP individuals presenting low nAb titers have recovered due to additional/complementary immune mechanisms (T‐cell response, cytokines) other than classical humoral response.…”

Section: Discussionmentioning

confidence: 99%

“…Even if nAb becomes undetectable in the future, it is likely that in re-exposure, both the memory and killer T cells will be engaged in secondary immunologic response. 32,45 It is possible that CCP individuals presenting low nAb titers have recovered due to additional/complementary immune mechanisms (T-cell response, cytokines) other than classical humoral response. Studies have demonstrated that SARS-CoV-2 re-infection in previously immune animals was capable of inducing a robust protective immune response, 37,40,46 showing that immunity is maintained and protective in subsequent exposures, although human protection might last for only a period of 1-2 years.…”

Section: Discussionmentioning

confidence: 99%

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A longitudinal study of convalescent plasma (CCP) donors and correlation of ABO group, initial neutralizing antibodies (nAb), and body mass index (BMI) with nAb and anti‐nucleocapsid (NP) SARS‐CoV‐2 antibody kinetics: Proposals for better quality of CCP collections

et al. 2021

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Introduction Little is known about the neutralizing (nAb) and binding antibody kinetics in COVID‐19 convalescent plasma donors, especially during the first 100 days after disease onset. Materials and Methods A cohort of previously RT‐PCR positive (detected by nasopharyngeal swab during the acute phase), male convalescent patients, all with mild symptoms, were enrolled in serial blood sample collection for a longitudinal nAb titers and anti‐nucleocapsid (NP) antibodies (IgM, IgG and IgA) evaluation. NAbs were detected by a cytopathic effect‐based virus neutralization test (CPE‐based VNT), carried out with SARS‐CoV‐2 (GenBank: MT350282). Results A total of 78 male volunteers provided 316 samples, spanning a total of 4820 days of study. Although only 25% of donors kept nAb titers ≥160 within 100 days after the onset of disease, there was >75% probability of sustaining nAb titers ≥160 in volunteers whose initial nAb titer was ≥1280, weight ≥ 90 kg or obese, according to their body mass index (BMI), as evidenced by Kaplan–Meier analysis and Cox hazard regression (all p < .02). There was no correlation between the ABO group, ABO antibody titers and persistent high nAb titers. High IgG anti‐NP (S/CO ≥5.0) is a good surrogate for detecting nAb ≥ 160, defined by the ROC curve (sensitivity = 90.5%; CI95%: 84.5%–94.7%). Conclusion Selection of CCP donors for multiple collections based on initial high nAb titers (≥1280) or BMI ≥ 30 kg/m 2 provides a simple strategy to achieve higher quality in CCP programs. High IgG anti‐NP levels can also be used as surrogate markers for high nAb screening.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A longitudinal study of convalescent plasma (CCP) donors and correlation of ABO group, initial neutralizing antibodies (nAb), and body mass index (BMI) with nAb and anti‐nucleocapsid (NP) SARS‐CoV‐2 antibody kinetics: Proposals for better quality of CCP collections

et al. 2021

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“…Ab-based therapeutics directed against SARS-CoV-2 still present lights and shadows 14 . Preclinical data and phase-III clinical studies indicate that mAbs could be effectively deployed for prevention or treatment during the viral symptoms phase of the disease 15 .…”

Section: Introductionmentioning

confidence: 99%

Molecular rationale for SARS-CoV-2 spike circulating mutations able to escape bamlanivimab and etesevimab monoclonal antibodies

Laurini

Aulić

Fermeglia

et al. 2021

Sci Rep

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The purpose of this work is to provide an in silico molecular rationale of the role eventually played by currently circulating mutations in the receptor binding domain of the SARS-CoV-2 spike protein (S-RBDCoV‑2) in evading the immune surveillance effects elicited by the two Eli Lilly LY-CoV555/bamlanivimab and LY-CoV016/etesevimab monoclonal antibodies. The main findings from this study show that, compared to the wild-type SARS-CoV-2 spike protein, mutations E484A/G/K/Q/R/V, Q493K/L/R, S494A/P/R, L452R and F490S are predicted to be markedly resistant to neutralization by LY-CoV555, while mutations K417E/N/T, D420A/G/N, N460I/K/S/T, T415P, and Y489C/S are predicted to confer LY-CoV016 escaping advantage to the viral protein. A challenge of our global in silico results against relevant experimental data resulted in an overall 90% agreement. Thus, the results presented provide a molecular-based rationale for all relative experimental findings, constitute a fast and reliable tool for identifying and prioritizing all present and newly reported circulating spike SARS-CoV-2 variants with respect to antibody neutralization, and yield substantial structural information for the development of next-generation vaccines and monoclonal antibodies more resilient to viral evolution.

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“…The waning nAb levels observed in this study does not mean that these individuals lost their immune status or will be susceptible to re-infections in the future, as they markedly are nAb producers; only their level is below a pre-defined cut-off for donation. Even if their nAb becomes undetectable in the future, it is likely that in re-exposure, both the memory and killer T-cells will be engaged in a secondary immunologic response 24, 46 . It is possible that CCP individuals who already presented with low nAb titers could have recovered due to additional/complementary immune mechanisms (T-cell response, cytokines, etc.)…”

Section: Discussionmentioning

confidence: 99%

Correlation of Body Mass Index (BMI), initial neutralizing antibodies (nAb), ABO group and kinetics of nAb and anti-nucleocapsid (NP) SARS-CoV-2 antibodies in convalescent plasma (CCP) donors – A longitudinal study with proposals for better quality of CCP collections

Wendel

Fontão-Wendel

Fachini

et al. 2020

Preprint

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IntroductionA cohort of COVID-19 convalescent volunteers allowed the study of neutralizing (nAb) and ligand antibodies kinetics by providing sequential samples during a median of 100 days after onset of disease.Material and MethodsA cohort of previously RT-PCR+ve (detected by nasopharyngeal swab during the acute phase), male convalescent patients, all with mild symptoms, were enrolled on serial blood sample collection for evaluation of longitudinal nAb titers and anti-nucleocapsid (NP) antibodies (IgM, IgG and IgA). Nabs were detected by a cytopathic effect-based virus neutralization test (CPE-based VNT), carried out with SARS-CoV-2 (GenBank: MT350282)ResultsA total of 78 male volunteers provided 316 samples, spanning a total of 4820 days of study. Although only 25% of donors kept nAb titers ≥160, after a median of 100 days after the onset of disease, there was a high probability of sustaining nAB titers ≥160 in volunteers whose initial nAb titer was ≥1280, weight ≥ 90kg or BMI classified as overweight or obese, evidenced by Kaplan-Meier estimates and Cox hazard regression. There was no correlation between ABO group, ABO antibody titers and persistent high nAb titers. High IgG anti-NP (S/CO ≥5.0) is a good surrogate for detecting nAB ≥160, defined by ROC curve (sensitivity = 90.5%; CI95% 84.5-94.7%)ConclusionSelection of CCP donors for multiple collections based on initial high nAb titers (≥1280) or overweight/obese (BMI) provides a simple strategy to achieve higher quality in CCP programs. High IgG anti-NP levels can also be used as surrogate markers for high nAb screening.

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Neutralizing Antibodies Against SARS-CoV-2—Important Questions, Unclear Answers

Abstract: A, et al. Evaluating the association of clinical characteristics with neutralizing antibody levels in patients who have recovered from mild COVID-19 in Shanghai, China.

Cited by 9 publications

References 1 publication

A longitudinal study of convalescent plasma (CCP) donors and correlation of ABO group, initial neutralizing antibodies (nAb), and body mass index (BMI) with nAb and anti‐nucleocapsid (NP) SARS‐CoV‐2 antibody kinetics: Proposals for better quality of CCP collections

A longitudinal study of convalescent plasma (CCP) donors and correlation of ABO group, initial neutralizing antibodies (nAb), and body mass index (BMI) with nAb and anti‐nucleocapsid (NP) SARS‐CoV‐2 antibody kinetics: Proposals for better quality of CCP collections

Molecular rationale for SARS-CoV-2 spike circulating mutations able to escape bamlanivimab and etesevimab monoclonal antibodies

Correlation of Body Mass Index (BMI), initial neutralizing antibodies (nAb), ABO group and kinetics of nAb and anti-nucleocapsid (NP) SARS-CoV-2 antibodies in convalescent plasma (CCP) donors – A longitudinal study with proposals for better quality of CCP collections

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