Predicting the Efficacy of COVID-19 Convalescent Plasma Donor Units with the Lumit Dx anti-Receptor Binding Domain Assay

Janaka, Sanath Kumar; Clark, Natasha M; Evans, David T.

doi:10.1101/2021.03.08.21253135

Cited by 5 publications

(3 citation statements)

References 29 publications

(25 reference statements)

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“…As reported by multiple studies so far, the neutralizing ability of antibodies in SARS-2 convalescent individuals differs highly from one individual to the next [ 35 , 47 , 48 ]. Furthermore, anti-S antibody titers as measured by antibody capture ELISA indicates that a majority of antibodies against the S protein is of the IgG subtype, with lower levels of the IgA and IgM subtypes.…”

Section: Discussionmentioning

confidence: 99%

Anti-SARS-CoV-2 IgG and IgA antibodies in COVID-19 convalescent plasma do not enhance viral infection

et al. 2022

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The novel coronavirus, SARS-CoV-2 that causes COVID-19 has resulted in the death of nearly 4 million people within the last 18 months. While preventive vaccination, and monoclonal antibody therapies have been rapidly developed and deployed, early in the pandemic the use of COVID-19 convalescent plasma (CCP) was a common means of passive immunization with a theoretical risk of antibody-dependent enhancement (ADE) of viral infection. Though vaccines elicit a strong and protective immune response and transfusion of CCP with high titers of neutralization activity are correlated with better clinical outcomes, the question of whether antibodies in CCP can enhance infection of SARS-CoV-2 has not been directly addressed. In this study, we analyzed for and observed passive transfer of neutralization activity with CCP transfusion. Furthermore, to specifically understand if antibodies against the spike protein (S) enhance infection, we measured the anti-S IgG, IgA, and IgM responses and adapted retroviral-pseudotypes to measure virus neutralization with target cells expressing the ACE2 virus receptor and the Fc alpha receptor (FcαR) or Fc gamma receptor IIA (FcγRIIA). Whereas neutralizing activity of CCP correlated best with higher titers of anti-S IgG antibodies, the neutralizing titer was not affected when Fc receptors were present on target cells. These observations support the absence of antibody-dependent enhancement of infection (ADE) by IgG and IgA isotypes found in CCP. The results presented, therefore, not only supports the therapeutic use of currently available antibody-based treatment, including the continuation of CCP transfusion strategies, but also the use of various vaccine platforms in a prophylactic approach.

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Section: Discussionmentioning

confidence: 99%

Anti-SARS-CoV-2 IgG and IgA antibodies in COVID-19 convalescent plasma do not enhance viral infection

et al. 2022

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“…Additionally, neutralizing antibody titer of most of the convalescent sera correlated to level of speci c binding antibody to RBD. Thus many anti-RBD assays were developed to use as a predictor of the neutralization capability (20)(21)(22).…”

Section: Discussionmentioning

confidence: 99%

Dynamics of Neutralizing Antibodies and Binding Antibodies to Domains of SARS-CoV-2 Spike Protein in COVID-19 Survivors

et al. 2022

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Neutralizing antibody level is used to predict immune protection against SARS-CoV-2 infection. Spike protein of SARS-CoV-2 is a major target for virusneutralizing antibody. A number of neutralizing epitopes were mapped on receptor binding domain (RBD) and N-terminal domain (NTD) of S1 subunit of the spike. Anti-SARS-CoV-2 antibody usually decreases over time after recovery. Level of neutralizing antibody and binding antibody to several domains from COVID-19 recovered patients were observed longitudinally in this study. Sequentially collected serum samples from 35 patients demonstrated both similar and different trends of neutralizing antibodies versus binding antibodies to each domain. Twenty-three individuals showed similarly decreasing pattern of neutralizing titer, binding antibodies to RBD, NTD, fusion protein (S2) and nucleocapsid (NP). Interestingly, eight individuals had stably high neutralizing titer (≥320) for 3-12 months, while their binding antibodies to RBD, NTD and NP rapidly decreased. Moreover, their binding antibodies to S2 were stable over time similar to the persistence of neutralizing antibody levels. The longer-lasting antibody to S2 suggested an anamnestic response to cross-reactive epitopes from previous infections with other related coronaviruses. These data indicate a difference in kinetics and longevity of antibodies to various domains and epitopes of the SARS-CoV 2 proteins. A better understanding in this difference may help improve vaccine design to induce long-lasting immunity to COVID-19.

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“…Cell-free neutralization assays to monitor SARS-CoV-2 neutralizing antibodies have also been developed like for example those commercialized by Meso Scale Diagnostics ( Johnson et al, 2020) or Promega ( Janaka, Clark, Evans, & Connor, 2021). Several other non-commercialized cell-free assays have furthermore been described (Danh et al, 2020;Fenwick et al, 2021;Mravinacova et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Nanoluciferase-based cell fusion assay for rapid and high-throughput assessment of SARS-CoV-2-neutralizing antibodies in patient samples

Meyrath

Szpakowska

Plesséria

et al. 2022

Methods in Enzymology

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Predicting the Efficacy of COVID-19 Convalescent Plasma Donor Units with the Lumit Dx anti-Receptor Binding Domain Assay

Cited by 5 publications

References 29 publications

Anti-SARS-CoV-2 IgG and IgA antibodies in COVID-19 convalescent plasma do not enhance viral infection

Anti-SARS-CoV-2 IgG and IgA antibodies in COVID-19 convalescent plasma do not enhance viral infection

Dynamics of Neutralizing Antibodies and Binding Antibodies to Domains of SARS-CoV-2 Spike Protein in COVID-19 Survivors

Nanoluciferase-based cell fusion assay for rapid and high-throughput assessment of SARS-CoV-2-neutralizing antibodies in patient samples

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