The landscape of antibody binding in SARS-CoV-2 infection

Heffron, Anna S.; McIlwain, Sean J.; Amjadi, Maya F.; Baker, David; Khullar, Saniya; Sethi, Ajay K.; Palmenberg, Ann C.; Shelef, Miriam A.; O’Connor, David H.; Ong, Irene M.

doi:10.1101/2020.10.10.334292

Cited by 15 publications

(15 citation statements)

References 68 publications

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“…An in-house ELISA targeting the RBD of the SARS-CoV-2 Spike protein was adapted from an assay designed to establish seropositivity of COVID-19 convalescent plasma (Perreault et al, 2020). SARS-CoV-2 Spike RBD was chosen over other SARS-CoV-2 antigens because of its low homology with common cold human coronaviruses, thus limiting cross-reactivity (Heffron et al, 2020;Prévost et al, 2020;Shrock et al, 2020). Assay design allows for the capture of the three main classes of immunoglobulins (IgG, IgA, and IgM).…”

Section: Anti-sars-cov-2 Spike Rbd Elisamentioning

confidence: 99%

SARS-CoV-2 seroprevalence among blood donors in Québec, and analysis of symptoms associated with seropositivity: a nested case-control study

Lewin

Therrien

Serres

et al. 2021

Can J Public Health

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Objectives A substantial proportion of individuals infected with SARS-CoV-2 do not experience noticeable symptoms typical of COVID-19. Our objectives were to evaluate the impact of the first wave of the pandemic in Québec by measuring SARS-CoV-2 antibody seroprevalence in a convenience sample of healthy blood donors and to study the association between seropositivity and the occurrence of COVID-19 symptoms. Methods The study design was a cross-sectional serological survey with a nested case-control study. Residual blood samples from donations collected between May 25 and July 9, 2020 (well before vaccination rollout) in the province of Québec were tested for anti-Spike RBD antibodies by ELISA. Seropositive donors and a control group of seronegative donors were questioned about prior COVID-19 symptoms. All qualified blood donors were eligible for participation. Results A total of 7691 blood donors were included in the study. After adjustments, the seroprevalence rate was 2.2% (95% CI 1.9-2.6). Seropositive donors reported one or more symptoms in a proportion of 52.2% (95% CI 44.2-60.1); this proportion was 19.1% (95% CI 13.4-26.1) among seronegative donors, suggesting that approximately 50-66% of all infections were asymptomatic. Univariate analysis of associations between symptoms and seropositivity revealed that except for rhinorrhea, all symptoms were significantly associated with seropositivity. Conclusion Assuming that blood donors are fairly representative of the general adult population, this study shows that less than 3% of 18-69-year-olds have been infected during the first wave of the pandemic in the province of Québec. Our data also confirm that many infections escaped detection, including a substantial proportion that were asymptomatic.

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Section: Anti-sars-cov-2 Spike Rbd Elisamentioning

confidence: 99%

SARS-CoV-2 seroprevalence among blood donors in Québec, and analysis of symptoms associated with seropositivity: a nested case-control study

Lewin

Therrien

Serres

et al. 2021

Can J Public Health

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“…Furthermore, despite most neutralizing Abs being RBD‐specific, 12–14 studies have isolated potent neutralizing Abs that are specific to other epitopes on the S trimer, mainly directed against the N‐terminal domain (NTD) of the S1 subunit 15 . In addition, the bulk of the Ab responses elicited by SARS‐CoV‐2 infection were found to target two major immunodominant regions on the S protein, the fusion peptide region and heptad repeat 2 of the S2 subunit 16,17 . Thus, current plasma screening processes using only recombinant RBD to determine seropositivity and Ab titers for convalescent plasma therapy could overlook Abs specific to multiple epitopes on the viral Spike.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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Background The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) virus is the cause of the ongoing coronavirus disease 2019 (COVID‐19) pandemic, infecting millions of people and causing more than two million deaths. The SARS‐CoV‐2 Spike glycoproteins mediate viral entry and represent the main target for antibody responses. Humoral responses were shown to be important for preventing and controlling infection by coronaviruses. A promising approach to reduce the severity of COVID‐19 is the transfusion of convalescent plasma. However, longitudinal studies revealed that the level of antibodies targeting the receptor‐binding domain (RBD) of the SARS‐CoV‐2 Spike declines rapidly after the resolution of the infection. Study Design and Methods To extend this observation beyond the RBD domain, we performed a longitudinal analysis of the persistence of antibodies targeting the full‐length SARS‐CoV‐2 Spike in the plasma from 15 convalescent donors. We generated a 293T cell line constitutively expressing the SARS‐CoV‐2 Spike and used it to develop a high‐throughput flow cytometry‐based assay to detect SARS‐CoV‐2 Spike‐specific antibodies in the plasma of convalescent donors. Results and Conclusion We found that the level of antibodies targeting the full‐length SARS‐CoV‐2 Spike declines gradually after the resolution of the infection. This decline was not related to the number of donations but strongly correlated with the decline of RBD‐specific antibodies and the number of days post‐symptom onset. These findings help to better understand the decline of humoral responses against the SARS‐CoV‐2 Spike and provide important information on when to collect plasma after recovery from active infection for convalescent plasma transfusion.

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“…The Spike (S) protein is a dominant immunoreactive protein and has several recognized regions, including the receptor binding domain [33][34][35][36][37][38][39]. Other recognized antigens commonly include Nucleocapsid (N), Membrane (M), orf3a, orf6, orf8, orf10, and Nsp5 (Mpro or 3CLpro) (Figure 1) [36,37,[39][40][41][42][43][44]. The latter may or may not include structural proteins of intact virus and may arise as proteins derived during the processes of infection.…”

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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The landscape of antibody binding in SARS-CoV-2 infection

Cited by 15 publications

References 68 publications

SARS-CoV-2 seroprevalence among blood donors in Québec, and analysis of symptoms associated with seropositivity: a nested case-control study

SARS-CoV-2 seroprevalence among blood donors in Québec, and analysis of symptoms associated with seropositivity: a nested case-control study

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

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

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