Microfluidic Affinity Profiling reveals a Broad Range of Target Affinities for Anti-SARS-CoV-2 Antibodies in Plasma of COVID-19 Survivors

Schneider, Matthias M.; Emmenegger, Marc; Xu, Catherine K.; Morales, Itzel Condado; Meisl, Georg; Turelli, Priscilla; Zografou, Chrysoula; Zimmermann, Manuela R; Frey, Beat M.; Fiedler, Sebastian; Denninger, Viola; Jacquat, Raphaël P. B.; Madrigal, Lidia; Ilsley, Alison; Kosmoliaptsis, Vasilis; Fiegler, Heike; Trono, Didier; Knowles, Tuomas P. J.; Aguzzi, Adriano

doi:10.1101/2020.09.20.20196907

Cited by 7 publications

(24 citation statements)

References 44 publications

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“…In resource‐constrained settings, it is hence possible to orient the wave of CCP donations so that time and resource wasting is minimized. This study was limited to clinical proxies, but several studies identified additional, serological (eg, anti‐Spike IgG avidity, r = .4, 22 or microfluidic affinity) 23 or non‐serological biomarkers (eg, high C‐reactive protein, r = .5) 15 : The utility of such specialistic laboratory biomarkers is reduced by their limited availability at the time of CCP donation screening, and, if unavailable, by their incremental cost, which largely overlap the one of high‐throughput serology.…”

Section: Discussionmentioning

confidence: 99%

Clinical predictors of SARS‐CoV‐2 neutralizing antibody titers in COVID‐19 convalescents: Implications for convalescent plasma donor recruitment

Focosi¹,

Franchini

2021

European J of Haematology

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While COVID‐19 convalescent plasma (CCP) efficacy is still under investigation in randomized controlled trials (RCT), CCP collections continue worldwide with largely variable criteria. Since it is well known that only a minority of patients develop high‐titer neutralizing antibodies (nAb), as assessed by the viral neutralization tests (VNT), strategies to maximize cost‐effectiveness of CCP collection are urgently needed. A growing amount of the population is having exposure to the virus and is hence becoming a candidate CCP donor. Laboratory screening with high‐throughput serology has good correlations with the VNT titer, but upstream screening using clinical surrogates would be advisable. We review here the existing literature on clinical predictors of high‐titer nAb. Older age, male sex, and hospitalization are the main proxies of high VNT and should drive CCP donor recruitment.

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Section: Discussionmentioning

confidence: 99%

Clinical predictors of SARS‐CoV‐2 neutralizing antibody titers in COVID‐19 convalescents: Implications for convalescent plasma donor recruitment

Focosi¹,

Franchini

2021

European J of Haematology

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“…In this assay, we used trimeric spike accounting not only the neutralizing antibodies targeting RBD sequence, but also additional epitopes which are suspected to contribute to the overall antibody response (9,11,33,34). To validate the assay, we used serum collected from 19 SARS-CoV-2 positive individuals 11-24 days after RT-PCR testing, a time window when seroconversion has been shown to occur (35)(36)(37)(38) and consistent with these previous reports, all but one of the 19 SARS-CoV-2 had seroconverted.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, it would have been logistically difficult to screen asymptomatic individuals outside a health care environment. It is a fact that we have used a limited number of SARS-CoV-2-positive individuals to setup our assays, however the number used is well within the one used in similar studies (3,11,31,32). In addition, variations of this ELISA test developed by Florian Krammer laboratory has been used by multiple groups worldwide.…”

Section: Discussionmentioning

confidence: 99%

“…Serological tests, which detect antibodies specific for SARS-CoV-2, allow for a more accurate estimate of the cumulative prevalence of SARS-CoV-2 infection in a population compared to the viral diagnostic test; as SARS-CoV-2 antibodies, in particular IgG, persist after viral clearance (7). Most of the SARS-CoV-2 serological tests developed so far detect antibodies made against the viral protein Spike (8)(9)(10)(11)(12)(13). Spike is a trimeric glycoprotein protruding from SARS-CoV-2 viral membrane that mediates viral entry into the host cell (14,15).…”

Section: Introductionmentioning

confidence: 99%

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Evaluating SARS-CoV-2 Seroconversion Following Relieve of Confinement Measures

et al. 2020

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Seroprevalence studies are crucial both for estimating the prevalence of SARS-CoV-2 exposure and to provide a measure for the efficiency of the confinement measures. Portuguese universities were closed on March 16th 2020, when Portugal only registered 62 SARS-CoV-2 infection cases per million. We have validated a SARS-CoV-2 ELISA assay to a stabilized full-length spike protein using 216 pre-pandemic and 19 molecularly diagnosed SARS-CoV-2 positive individual's samples. At NOVA University of Lisbon, presential work was partially resumed on May 25th with staggered schedules. From June 15th to 30th, 3–4 weeks after the easing of confinement measures, we screened 1,636 collaborators of NOVA university of Lisbon for the presence of SARS-CoV-2 spike specific IgA and IgG antibodies. We found that spike-specific IgG in 50 of 1,636 participants (3.0%), none of which had anti-spike IgA antibodies. As participants self-reported as asymptomatic or paucisymptomatic, our study also provides a measurement of the prevalence of asymptomatic/paucisymptomatic SARS-CoV-2 infections. Our study suggests that essential workers have a 2-fold increase in viral exposure, when compared to non-essential workers that observed confinement. Additional serological surveys in different population subgroups will paint a broader picture of the effect of the confinement measures in the broader community.

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“…In contrast, the RBD-beta-ACE2 complex lacks salt bridges between RBD-beta K417 and ACE2 D30 and between RBD-beta E484 and ACE2 K31, which seems to counteract the increased ACE2 affinity mediated by N501Y 16 . 18,19 . Error bars are 95% credible intervals.…”

Section: Pmentioning

confidence: 99%

Mutations in two SARS-CoV-2 variants of concern reflect two distinct strategies of antibody escape

Fiedler¹,

Denninger²,

Morgunov

et al. 2021

Preprint

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Understanding the factors that contribute to antibody escape of SARS-CoV-2 and its variants is key for the development of drugs and vaccines that provide broad protection against a variety of virus variants. Using microfluidic diffusional sizing, we determined the dissociation constant ((KD)) for the interaction between receptor binding domains (RBDs) of SARS-CoV-2 in its original version (WT) as well as alpha and beta variants with the host-cell receptor angiotensin converting enzyme 2 (ACE2). For RBD-alpha, the ACE2-binding affinity was increased by a factor of ten when compared with RBD-WT, while ACE2-binding of RBD-beta was largely unaffected. However, when challenged with a neutralizing antibody that binds to both RBD-WT and RBD-alpha with low nanomolar (KD) values, RBD-beta displayed no binding, suggesting a substantial epitope change. In SARS-CoV-2 convalescent sera, RBD-binding antibodies showed low nanomolar affinities to both wild-type and variant RBD proteins—strikingly, the concentration of antibodies binding to RBD-beta was half that of RBD-WT and RBD-alpha, again indicating considerable epitope changes in the beta variant. Our data therefore suggests that one factor contributing to the higher transmissibility and antibody evasion of SARS-CoV-2 alpha and beta is a larger fraction of viruses that can form a complex with ACE2. However, the two variants employ different mechanisms to achieve this goal. While SARS-CoV-2 alpha RBD binds with greater affinity to ACE2 and is thus more difficult to displace from the receptor by neutralizing antibodies, RBD-beta is less accessible to antibodies due to epitope changes which increases the chances of ACE2-binding and infection.

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Microfluidic Affinity Profiling reveals a Broad Range of Target Affinities for Anti-SARS-CoV-2 Antibodies in Plasma of COVID-19 Survivors

Cited by 7 publications

References 44 publications

Clinical predictors of SARS‐CoV‐2 neutralizing antibody titers in COVID‐19 convalescents: Implications for convalescent plasma donor recruitment

Clinical predictors of SARS‐CoV‐2 neutralizing antibody titers in COVID‐19 convalescents: Implications for convalescent plasma donor recruitment

Evaluating SARS-CoV-2 Seroconversion Following Relieve of Confinement Measures

Mutations in two SARS-CoV-2 variants of concern reflect two distinct strategies of antibody escape

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