Two-tiered SARS-CoV-2 seroconversion screening in the Netherlands and stability of nucleocapsid, spike protein domain 1 and neutralizing antibodies

Garritsen, Anja; Scholzen, Anja; Nieuwenhof, Daan W.A. van den; Smits, Anke P.F.; Datema, E. Suzan; Galen, Luc S. van; Kouwijzer, Milou

doi:10.1101/2020.10.07.20187641

Cited by 8 publications

(7 citation statements)

References 71 publications

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“…In agreement with this hypothesis, correlation between neutralization and RBD and S1 IgG levels, measured by Luminex assay, showed slightly higher coefficients and lower pvalues at 10 weeks PO than at 6 weeks PO (Figure 2C). Similarly, Garritsen et al found higher stability of sera neutralizing antibody as compared to S1 IgG levels in two tests performed separated 46 -96 days, at various times after infection (34). However, other studies have found a decline in neutralizing antibodies at times after exposure that were similar to this study (10,24) which could be attributed to different study populations and clinical differences.…”

Section: Discussionsupporting

confidence: 64%

Antibody Responses to SARS-CoV-2 Following an Outbreak Among Marine Recruits With Asymptomatic or Mild Infection

et al. 2021

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We investigated serological responses following a SARS-CoV-2 outbreak in spring 2020 on a US Marine recruit training base. 147 participants that were isolated during an outbreak of respiratory illness were enrolled in this study, with visits approximately 6 and 10 weeks post-outbreak (PO). This cohort is comprised of young healthy adults, ages 18-26, with a high rate of asymptomatic infection or mild symptoms, and therefore differs from previously reported longitudinal studies on humoral responses to SARS-CoV-2, which often focus on more diverse age populations and worse clinical presentation. 80.9% (119/147) of the participants presented with circulating IgG antibodies against SARS-CoV-2 spike (S) receptor-binding domain (RBD) at 6 weeks PO, of whom 97.3% (111/114) remained positive, with significantly decreased levels, at 10 weeks PO. Neutralizing activity was detected in all sera from SARS-CoV-2 IgG positive participants tested (n=38) at 6 and 10 weeks PO, without significant loss between time points. IgG and IgA antibodies against SARS-CoV-2 RBD, S1, S2, and the nucleocapsid (N) protein, as well neutralization activity, were generally comparable between those participants that had asymptomatic infection or mild disease. A multiplex assay including S proteins from SARS-CoV-2 and related zoonotic and human endemic betacoronaviruses revealed a positive correlation for polyclonal cross-reactivity to S after SARS-CoV-2 infection. Overall, young adults that experienced asymptomatic or mild SARS-CoV-2 infection developed comparable humoral responses, with no decrease in neutralizing activity at least up to 10 weeks after infection.

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Section: Discussionsupporting

confidence: 64%

Antibody Responses to SARS-CoV-2 Following an Outbreak Among Marine Recruits With Asymptomatic or Mild Infection

et al. 2021

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“…Independently of the disease trajectory, the majority of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections trigger a response of the adaptive immune system [2][3][4] . Essential for this immune response are antibodies that neutralize SARS-CoV-2 (NAbs) by preventing virus binding to the host-cell receptor angiotensin-converting enzyme 2 (ACE2) [5][6][7][8][9][10][11][12][13] .…”

Section: Introductionmentioning

confidence: 99%

In vitro measurements of protein–protein interactions show that antibody affinity governs the inhibition of SARS-CoV-2 spike/ACE2 binding in convalescent serum

Fiedler¹,

Piziorska²,

Denninger³

et al. 2020

Preprint

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The humoral immune response plays a key role in suppressing the pathogenesis of SARS-CoV-2. The molecular determinants underlying the neutralization of the virus remain, however, incompletely understood. Here, we show that the ability of antibodies to disrupt the binding of the viral spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor on the cell, the key molecular event initiating SARS-CoV-2 entry into host cells, is controlled by the affinity of these antibodies to the viral antigen. By using microfluidic antibody-affinity profiling, we were able to quantify the serum-antibody mediated inhibition of ACE2–spike binding in two SARS-CoV-2 seropositive individuals. Measurements to determine the affinity, concentration, and neutralization potential of antibodies were performed directly in human serum. Using this approach, we demonstrate that the level of inhibition in both samples can be quantitatively described using the binding energies of the binary interactions between the ACE2 receptor and the spike protein, and the spike protein and the neutralizing antibody. These experiments represent a new type of in-solution receptor binding competition assay, which has further potential areas of application ranging from decisions on donor selection for convalescent plasma therapy, to identification of lead candidates in therapeutic antibody development, and vaccine development.

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“…It is also important to consider that here we analyzed samples from individuals who presented mild symptoms and were fully recovered, which may explain the lower incidence observed for some immunoglobulin isotypes, as antibody titers strongly correlates with disease severity [42,43,44]. Indeed, studies performed with hospitalized patients have reported up to 94% seroconversion of against N protein [45,46,47].…”

Section: Discussionmentioning

confidence: 99%

On the caveats of a multiplex test for SARS-CoV-2 to detect seroconversion after infection or vaccination

Fernandes-Siqueira

Abdalla

Sousa

et al. 2022

Preprint

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The Covid-19 pandemic, caused by SARS-CoV-2, resulted in more than 5 million deaths being one of the biggest challenges the world faces today. Here we present optimizations to all steps of an enzyme-linked immunosorbent assay (ELISA)-based test to detect IgG, IgA and IgM against the trimeric spike (S) protein, receptor binding domain (RBD), and N terminal domain of the nucleocapsid (N-NTD) protein of SARS-CoV-2. We discuss how to determine the specific thresholds for antibody positivity and its limitations according to the antigen used. We applied the assay in a cohort of 126 individuals from Rio de Janeiro, Brazil, consisting of 23 PCR-positive individuals; and 103 individuals without confirmed diagnosis for SARS-CoV-2 infection. To illustrate the differences in serological responses to vaccinal immunization, we applied the test in 18 individuals of our cohort before and after receive ChAdOx-1 nCoV-19 or CoronaVac vaccines. Taken together, our results show that the test can be customized at different stages depending on its application, enabling the user to analyze different cohorts, saving time, reagents, or samples. It also represents a valuable tool for elucidating the immunological consequences of new viral strains and for monitoring vaccination coverage and the duration of response to different immunization regimens.

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Two-tiered SARS-CoV-2 seroconversion screening in the Netherlands and stability of nucleocapsid, spike protein domain 1 and neutralizing antibodies

Cited by 8 publications

References 71 publications

Antibody Responses to SARS-CoV-2 Following an Outbreak Among Marine Recruits With Asymptomatic or Mild Infection

Antibody Responses to SARS-CoV-2 Following an Outbreak Among Marine Recruits With Asymptomatic or Mild Infection

In vitro measurements of protein–protein interactions show that antibody affinity governs the inhibition of SARS-CoV-2 spike/ACE2 binding in convalescent serum

On the caveats of a multiplex test for SARS-CoV-2 to detect seroconversion after infection or vaccination

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