High‐throughput detection of antibodies targeting the <scp>SARS‐CoV</scp>‐2 <scp>Spike</scp> in longitudinal convalescent plasma samples

Anand, Sai Priya; Prévost, Jérémie; Richard, Jonathan; Perreault, Josée; Tremblay, Tony; Drouin, Mathieu; Fournier, Marie-Josée; Lewin, Antoine; Bazin, Renée; Finzi, Andrés

doi:10.1111/trf.16318

Cited by 19 publications

(18 citation statements)

References 29 publications

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“…We assessed immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies against the receptor binding domain (RBD) of SARS-CoV-2 spike glycoprotein in plasma samples using an enzyme-linked immunosorbent assay (ELISA), as previously described. [14][15][16] Receptor binding domain is required for SARS-CoV-2 to bind to the host angiotensin-converting enzyme 2 (ACE-2) receptor allowing viral entry and represents the target of the BNT162b2 vaccine. 5 We chose anti-RBD antibodies as they have been shown to elicit viral neutralization better than anti-spike antibodies.…”

Section: Antibody Measurementsmentioning

confidence: 99%

“…We reported anti-RBD IgG and IgM levels as relative light units (RLU) normalized to CR3022 mAb. [14][15][16] We established the seropositive threshold as the mean RLU from COVID-19 negative plasma obtained from 10 volunteers prepandemic, plus 3 standard deviations above this mean. 14,15 We have previously shown excellent reliability of this assay in detecting anti-RBD IgG levels in a cross-sectional cohort of individuals infected with SARS-CoV-2: anti-RBD IgG levels were detectable with this assay in 85% of infected individuals at 14 days, and in 100% by 53 days after symptom onset.…”

Section: Antibody Measurementsmentioning

confidence: 99%

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Short-term antibody response after 1 dose of BNT162b2 vaccine in patients receiving hemodialysis

Goupil

Benlarbi

Beaubien‐Souligny

et al. 2021

CMAJ

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BACKGROUND: Patients receiving in-R E S U L T S : O u r s t u d y i n c l u d e d after vaccination.Among those with centre hemodialysis are at high risk of 154 patients receiving hemodialysis previous SARS-CoV-2 infection, median exposure to SARS-CoV-2 and death if (135 without and 19 with previous SARS-anti-RBD IgG levels at 8 weeks in infected. One dose of the BNT162b2 SARS-CoV-2 infection), 40 controls (20 without patients receiving hemodialysis were CoV-2 vaccine is eficacious in the general and 20 with previous SARS-CoV-2 infec-similar to controls at 3 weeks (p = 0.3) population, but responses in patients tion) and convalescent plasma from and to convalescent plasma (p = 0.8). receiving hemodialysis are uncertain. 16 patients. Among those without previous SARS-CoV-2 infection, anti-RBD IgG INTERPRETATION: A single dose of METHODS: We obtained serial plasma was undetectable at 4 weeks in 75 of BNT162b2 vaccine failed to elicit a from patients receiving hemodialysis and 131 (57%, 95% confidence interval [CI] humoral immune response in most health care worker controls before and 47% to 65%) patients receiving hemodipatients receiving hemodialysis without after vaccination with 1 dose of the alysis, compared with 1 of 20 (5%, 95% previous SARS-CoV-2 infection, even BNT162b2 mRNA vaccine, as well as con-CI 1% to 23%) controls (p < 0.001). No after prolonged observation. In those valescent plasma from patients receiving patient with nondetectable levels at with previous SARS-CoV-2 infection, the hemodialysis who survived COVID-19. We 4 weeks developed anti-RBD IgG by antibody response was delayed. We measured anti-receptor binding domain 8 weeks. Results were similar in nonadvise that patients receiving hemodi-(RBD) immunoglobulin G (IgG) levels and immunosuppressed and younger indialysis be prioritized for a second stratified groups by evidence of previous viduals. Three patients receiving hemo-BNT162b2 dose at the recommended SARS-CoV-2 infection. dialysis developed severe COVID-19 3-week interval. Patients with end-stage kidney disease receiving in-this population. Some hemodialysis centres have thus prioricentre hemodialysis have been uniquely vulnerable dur-tized these patients for vaccination. ing the COVID-19 pandemic. For these patients, unlikeTo facilitate wider vaccine distribution during current shortfor most other people, self-isolation to avoid exposure to SARS-ages, 3 the National Advisory Committee on Immunization of Can-CoV-2 is impossible. Most patients receiving hemodialysis must ada has recommended delaying the second dose of the leave their homes 3 times weekly to receive their life-saving BNT162b2 vaccine from 3 to 16 weeks. 4 In a randomized contreatments, ofen in shared spaces for hours at a time. COVID-19 trolled trial (RCT), the clinical efficacy of the BNT162b2 was case fatality rates are 20%-30% for patients receiving hemodireported to be greater than 80% at 3 weeks afer the first dose. 5 alysis -10 times higher than in the general population. 1,2 However, no patients receiving hemodial...

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Section: Antibody Measurementsmentioning

confidence: 99%

Section: Antibody Measurementsmentioning

confidence: 99%

Short-term antibody response after 1 dose of BNT162b2 vaccine in patients receiving hemodialysis

Goupil

Benlarbi

Beaubien‐Souligny

et al. 2021

CMAJ

Self Cite

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“…The majority of NAbs bind to the receptor binding domain (RBD) in the S1 subunit for inhibiting virus attachment to the human Angiotensin Converting Enzyme 2 (hACE2) receptor. NAbs against the N-terminal domain (NTD) of S1 as well as the S2 subunit have also been isolated (Anand et al, 2021b;Liu et al, 2020;Voss et al, 2020). NAbs have demonstrated varying levels of efficacy and protection in multiple animal models of SARS-CoV-2 (Alsoussi et al, 2020;Baum et al, 2020;Fagre et al, 2020;Hansen et al, 2020;Hassan et al, 2020;Li et al, 2020;Rogers et al, 2020;Shi et al, 2020b;Winkler et al, 2020;Zost et al, 2020a;Zost et al, 2020b).…”

Section: Introductionmentioning

confidence: 99%

Live Imaging of SARS-CoV-2 Infection in Mice Reveals Neutralizing Antibodies Require Fc Function for Optimal Efficacy

Ullah

Prévost

Ladinsky

et al. 2021

Preprint

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Neutralizing antibodies (NAbs) are effective in treating COVID-19 but the mechanism of immune protection is not fully understood. Here, we applied live bioluminescence imaging (BLI) to monitor the real-time effects of NAb treatment in prophylaxis and therapy of K18-hACE2 mice intranasally infected with SARS-CoV-2-nanoluciferase. We visualized sequential spread of virus from the nasal cavity to the lungs followed by systemic spread to various organs including the brain, culminating in death. Highly potent NAbs from a COVID-19 convalescent subject prevented, and also effectively resolved, established infection when administered within three days of infection. In addition to direct neutralization, in vivo efficacy required Fc effector functions of NAbs, with contributions from monocytes, neutrophils and natural killer cells, to dampen inflammatory responses and limit immunopathology. Thus, our study highlights the requirement of both Fab and Fc effector functions for an optimal in vivo efficacy afforded by NAbs against SARS-CoV-2.

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“…Different antibody responses decay variably and dependent on the nature of the antibody target and severity of disease [33,50,54,59,61,68,75,76,78,83,87,95,96,[100][101][102][103]. The latter includes measurable neutralizing antibody, and the decay in some patients after 1 month can be such that donations with desirable high titres elapse quickly in convalescence after infection [49,54,[103][104][105][106].…”

Section: Immunogens and Humoral Immunitymentioning

confidence: 99%

Passive Immunity Should and Will Work for COVID-19 for Some Patients

Cimolai¹

2021

CHI

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In the absence of effective antiviral chemotherapy and still in the context of emerging vaccines for severe acute respiratory syndrome-CoV-2 infections, passive immunotherapy remains a key treatment and possible prevention strategy. What might initially be conceived as a simplified donor-recipient process, the intricacies of donor plasma, IV immunoglobulins, and monoclonal antibody modality applications are becoming more apparent. Key targets of such treatment have largely focused on virus neutralization and the specific viral components of the attachment Spike protein and its constituents (e.g., receptor binding domain, N-terminal domain). The cumulative laboratory and clinical experience suggests that beneficial protective and treatment outcomes are possible. Both a dose-and a time-dependency emerge. Lesser understood are the concepts of bioavailability and distribution. Apart from direct antigen binding from protective immunoglobulins, antibody effector functions have potential roles in outcome. In attempting to mimic the natural but variable response to infection or vaccination, a strong functional polyclonal approach attracts the potential benefits of attacking antigen diversity, high antibody avidity, antibody persistence, and protection against escape viral mutation. The availability and ease of administration for any passive immunotherapy product must be considered in the current climate of need. There is never a perfect product, but yet there is considerable room for improving patient outcomes. Given the variability of human genetics, immunity, and disease, and given the nuances of the virus and its potential for change, passive immunotherapy can be developed that will be effective for some but not all patients. An understanding of such patient variability and limitations is just as important as the understanding of the direct interactions between immunotherapy and virus.

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High‐throughput detection of antibodies targeting the SARS‐CoV‐2 Spike in longitudinal convalescent plasma samples

Cited by 19 publications

References 29 publications

Short-term antibody response after 1 dose of BNT162b2 vaccine in patients receiving hemodialysis

Short-term antibody response after 1 dose of BNT162b2 vaccine in patients receiving hemodialysis

Live Imaging of SARS-CoV-2 Infection in Mice Reveals Neutralizing Antibodies Require Fc Function for Optimal Efficacy

Passive Immunity Should and Will Work for COVID-19 for Some Patients

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