A simple protein-based surrogate neutralization assay for SARS-CoV-2

Abe, Kento T.; Li, Zhijie; Samson, Reuben; Samavarchi-Tehrani, Payman; Valcourt, Emelissa J.; Wood, Heidi; Budylowski, Patrick; Dupuis, Alan P.; Girardin, Roxie C.; Rathod, Bhavisha; Wang, Jenny H.; Barrios‐Rodiles, Miriam; Colwill, Karen; McGeer, Allison; Mubareka, Samira; Gommerman, Jennifer L.; Durocher, Yves; Ostrowski, Mario; McDonough, Kathleen A.; Drebot, Michael A.; Drews, Steven J.; Rini, James M.; Gingras, Anne‐Claude

doi:10.1172/jci.insight.142362

Cited by 199 publications

(166 citation statements)

References 40 publications

(38 reference statements)

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“…This test kit is advertised to test for pan-Ig neutralizing antibodies using the SARS-CoV-2 RBD as the viral antigen for antibody capture (82). Other promising surrogate neutralization assays have been proposed which utilize an ELISA-based competition binding assay against ACE2 (83,84). Antibodies against RBD have been shown to be the primary source of neutralizing antibodies against the virus (53,(85)(86)(87)(88).…”

Section: Neutralization Assays and Their Importancementioning

confidence: 99%

Humoral Responses and Serological Assays in SARS-CoV-2 Infections

et al. 2020

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In December 2019, the novel betacoronavirus Severe Acute Respiratory Disease Coronavirus 2 (SARS-CoV-2) was first detected in Wuhan, China. SARS-CoV-2 has since become a pandemic virus resulting in hundreds of thousands of deaths and deep socioeconomic implications worldwide. In recent months, efforts have been directed towards detecting, tracking, and better understanding human humoral responses to SARS-CoV-2 infection. It has become critical to develop robust and reliable serological assays to characterize the abundance, neutralization efficiency, and duration of antibodies in virus-exposed individuals. Here we review the latest knowledge on humoral immune responses to SARS-CoV-2 infection, along with the benefits and limitations of currently available commercial and laboratory-based serological assays. We also highlight important serological considerations, such as antibody expression levels, stability and neutralization dynamics, as well as cross-reactivity and possible immunological back-boosting by seasonal coronaviruses. The ability to accurately detect, measure and characterize the various antibodies specific to SARS-CoV-2 is necessary for vaccine development, manage risk and exposure for healthcare and at-risk workers, and for monitoring reinfections with genetic variants and new strains of the virus. Having a thorough understanding of the benefits and cautions of standardized serological testing at a community level remains critically important in the design and implementation of future vaccination campaigns, epidemiological models of immunity, and public health measures that rely heavily on up-to-date knowledge of transmission dynamics.

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Section: Neutralization Assays and Their Importancementioning

confidence: 99%

Humoral Responses and Serological Assays in SARS-CoV-2 Infections

et al. 2020

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“…In contrast, the two betacoronaviruses OC43 and HKU1 bind glycan receptors via the spike's N-terminal domain (NTD, also known as S1-A) [34]. Antibodies that block receptor binding dominate the neutralizing activity of immunity elicited by SARS-CoV-2 infection [35][36][37], so we reasoned that even though SARS-CoV-2 is a betacoronavirus, its antigenic evolution is more likely to be foreshadowed by the two human alphacoronaviruses that also use their RBD to bind a protein receptor. Of these two viruses, we chose 229E since it was first identified in humans >50 years ago [38], whereas NL63 was only identified in 2003 [39].…”

Section: Phylogenetic Analysis Of 229e Spikes To Identify Historical Strains For Experimental Studymentioning

confidence: 99%

A human coronavirus evolves antigenically to escape antibody immunity

et al. 2021

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There is intense interest in antibody immunity to coronaviruses. However, it is unknown if coronaviruses evolve to escape such immunity, and if so, how rapidly. Here we address this question by characterizing the historical evolution of human coronavirus 229E. We identify human sera from the 1980s and 1990s that have neutralizing titers against contemporaneous 229E that are comparable to the anti-SARS-CoV-2 titers induced by SARS-CoV-2 infection or vaccination. We test these sera against 229E strains isolated after sera collection, and find that neutralizing titers are lower against these “future” viruses. In some cases, sera that neutralize contemporaneous 229E viral strains with titers >1:100 do not detectably neutralize strains isolated 8–17 years later. The decreased neutralization of “future” viruses is due to antigenic evolution of the viral spike, especially in the receptor-binding domain. If these results extrapolate to other coronaviruses, then it may be advisable to periodically update SARS-CoV-2 vaccines.

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“…The short duration of neutralizing antibody titers within months may have important implications for immunity and ongoing efforts to deploy CP for prevention and therapy of COVID-19 [165]. There is a significant correlation to various extents between ELISA-measured immunoglobulin (IgG) titer and neutralizing antibody titer [87,257,274,276,[278][279][280][283][284][285]288,289]. However, the ELISA-determined anti-SARS-CoV-2 IgG did not always inhibit the virus receptor binding [259].…”

mentioning

confidence: 99%

Convalescent Plasma for the Prevention and Treatment of COVID-19: A Systematic Review and Quantitative Analysis

Peng¹,

Rhind²,

Beckett³

2021

JMIR Public Health Surveill

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Background The COVID-19 pandemic, caused by a novel coronavirus termed SARS-CoV-2, has spread quickly worldwide. Convalescent plasma (CP) obtained from patients following recovery from COVID-19 infection and development of antibodies against the virus is an attractive option for either prophylactic or therapeutic treatment, since antibodies may have direct or indirect antiviral activities and immunotherapy has proven effective in principle and in many clinical reports. Objective We seek to characterize the latest advances and evidence in the use of CP for COVID-19 through a systematic review and quantitative analysis, identify knowledge gaps in this setting, and offer recommendations and directives for future research. Methods PubMed, Web of Science, and Embase were continuously searched for studies assessing the use of CP for COVID-19, including clinical studies, commentaries, reviews, guidelines or protocols, and in vitro testing of CP antibodies. The screening process and data extraction were performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Quality appraisal of all clinical studies was conducted using a universal tool independent of study designs. A meta-analysis of case-control and randomized controlled trials (RCTs) was conducted using a random-effects model. Results Substantial literature has been published covering various aspects of CP therapy for COVID-19. Of the references included in this review, a total of 243 eligible studies including 64 clinical studies, 79 commentary articles, 46 reviews, 19 guidance and protocols, and 35 in vitro testing of CP antibodies matched the criteria. Positive results have been mostly observed so far when using CP for the treatment of COVID-19. There were remarkable heterogeneities in the CP therapy with respect to patient demographics, donor antibody titers, and time and dose of CP administration. The studies assessing the safety of CP treatment reported low incidence of adverse events. Most clinical studies, in particular case reports and case series, had poor quality. Only 1 RCT was of high quality. Randomized and nonrandomized data were found in 2 and 11 studies, respectively, and were included for meta-analysis, suggesting that CP could reduce mortality and increase viral clearance. Despite promising pilot studies, the benefits of CP treatment can only be clearly established through carefully designed RCTs. Conclusions There is developing support for CP therapy, particularly for patients who are critically ill or mechanically ventilated and resistant to antivirals and supportive care. These studies provide important lessons that should inform the planning of well-designed RCTs to generate more robust knowledge for the efficacy of CP in patients with COVID-19. Future research is necessary to fill the knowledge gap regarding prevention and treatment for patients with COVID-19 with CP while other therapeutics are being developed.

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A simple protein-based surrogate neutralization assay for SARS-CoV-2

Cited by 199 publications

References 40 publications

Humoral Responses and Serological Assays in SARS-CoV-2 Infections

Humoral Responses and Serological Assays in SARS-CoV-2 Infections

A human coronavirus evolves antigenically to escape antibody immunity

Convalescent Plasma for the Prevention and Treatment of COVID-19: A Systematic Review and Quantitative Analysis

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