scholarly journals Durability of Viral Neutralization in Asymptomatic Coronavirus Disease 2019 for at Least 60 Days

2021 ◽  
Author(s):  
Amanda Haymond ◽  
Abdulla A Damluji ◽  
Aarthi Narayanan ◽  
Claudius Mueller ◽  
Alex Reeder ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Immunoglobulin G ◽  
Neutralizing Antibodies ◽  
Healthcare Workers ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Serum Samples ◽  
Viral Neutralization ◽  
Time Period

Abstract A cohort consisting of asymptomatic healthcare workers donated temporal serum samples after infection with severe acute respiratory syndrome coronavirus 2. Analysis shows that all asymptomatic healthcare workers had neutralizing antibodies, that these antibodies persist for ≥60 days, and that anti-spike receptor-binding domain immunoglobulin G levels were correspondingly durable over the same time period.

scholarly journals Cross-reactive neutralization of SARS-CoV-2 by serum antibodies from recovered SARS patients and immunized animals

2020 ◽  
Vol 6 (45) ◽  
pp. eabc9999 ◽  
Author(s):  
Yuanmei Zhu ◽  
Danwei Yu ◽  
Yang Han ◽  
Hongxia Yan ◽  
Huihui Chong ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Binding Domain ◽  
Full Length ◽  
Receptor Binding Domain ◽  
Serum Antibodies ◽  
Serum Samples ◽  
S Protein ◽  
Novel Coronavirus

The current coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus genetically close to SARS-CoV. To investigate the effects of previous SARS-CoV infection on the ability to recognize and neutralize SARS-CoV-2, we analyzed 20 convalescent serum samples collected from individuals infected with SARS-CoV during the 2003 SARS outbreak. All patient sera reacted strongly with the S1 subunit and receptor binding domain (RBD) of SARS-CoV; cross-reacted with the S ectodomain, S1, RBD, and S2 proteins of SARS-CoV-2; and neutralized both SARS-CoV and SARS-CoV-2 S protein–driven infections. Analysis of antisera from mice and rabbits immunized with a full-length S and RBD immunogens of SARS-CoV verified cross-reactive neutralization against SARS-CoV-2. A SARS-CoV–derived RBD from palm civets elicited more potent cross-neutralizing responses in immunized animals than the RBD from a human SARS-CoV strain, informing strategies for development of universal vaccines against emerging coronaviruses.

scholarly journals Effect of RBD (Y453F) mutation in spike glycoprotein of SARS-CoV-2 on neutralizing IgG affinity

2021 ◽  
Author(s):  
Takuma Hayashi ◽  
Nobuo Yaegashi ◽  
Ikuo Konishi
Keyword(s):  
Monoclonal Antibodies ◽  
Structural Analysis ◽  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Virus Disease ◽  
Three Dimensional ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein

AbstractBackgroundInfection with receptor binding domain (RBD) mutant (Y453F) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from farmed minks is known to widely spread among humans.MethodsWe investigated the characteristics of SARS-CoV-2 RBD Y453F mutant using three- dimensional structural analysis. We investigated the effect of the RBD Y453F mutant of SARS-CoV- 2 on neutralizing antibodies in serum derived from Corona virus Disease 2019 (COVID-19) positive patients.ResultsOur studies suggest that virus variants with RBD Y453F mutation partially escaped detection by four neutralizing monoclonal antibodies and neutralizing antibodies in serum.ConclusionsConsequently, raising a concern that infection of SARS-CoV-2 mutants that cause serious symptoms in humans may spread globally.

scholarly journals The serological diversity of serum IgG/IgA/IgM against the SARS-CoV-2 nucleoprotein, spike, and receptor-binding domain and neutralizing antibodies in patients with COVID-19 in Japan

2021 ◽  
Author(s):  
Yudai Kaneko ◽  
Akira Sugiyama ◽  
Toshiya Tanaka ◽  
Kazushige Fukui ◽  
Akashi Taguchi ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Early Stage ◽  
Binding Domain ◽  
Structural Proteins ◽  
Receptor Binding Domain ◽  
Antibody Testing ◽  
Serum Samples ◽  
Iga Antibodies

Objectives: To compare the temporal changes of IgM, IgG, and IgA antibodies against the SARS-CoV-2 nucleoprotein, S1 subunit, and receptor binding domain and neutralizing antibodies (NAbs) against SARS-CoV-2 in patients with COVID-19. Methods: A total of five patients in Nissan Tamagawa Hospital, Tokyo, Japan confirmed COVID-19 from August 8, 2020 to August 14, 2020 were investigated. Serum samples were acquired multiple times from 0 to 76 days after symptom onset. Using a fully automated CLIA analyzer, we measured the levels of IgG, IgA, and IgM against the SARS-CoV-2 N, S1, and RBD and NAbs against SARS-CoV-2. Results: The levels of IgG antibodies against SARS-CoV-2 structural proteins increased over time in all cases but IgM and IgA levels against SARS-CoV-2 showed different increasing trends among individuals in the early stage. In particular, we observed IgA antibodies increasing before IgG and IgM in 3/5 cases. The NAb levels against SARS-CoV-2 increased and kept above 10 AU/mL more than around 70 days after symptom onset in all cases. Furthermore, in the early stage, NAb levels were more than cut off value in 4/5 COVID-19 patients some of whose antibodies against RBD didn't exceed 10 AU/mL. Conclusions: Our findings indicate that patients with COVID-19 should be examined for IgG, IgA and IgM antibodies against SARS-CoV-2 structural proteins and NAbs against SARS-CoV-2 in addition to conventional antibody testing methods for SARS-CoV-2 (IgG and IgM kits) to analyze the diversity of patients' immune mechanisms.

scholarly journals Cohabitation With a Known Coronavirus Disease 2019 Case Is Associated With Greater Antibody Concentration and Symptom Severity in a Community-Based Sample of Seropositive Adults

2021 ◽  
Vol 8 (7) ◽  
Author(s):  
Joshua M Schrock ◽  
Daniel T Ryan ◽  
Rana Saber ◽  
Nanette Benbow ◽  
Lauren A Vaught ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Immunoglobulin G ◽  
Symptom Severity ◽  
Binding Domain ◽  
Antibody Concentration ◽  
Receptor Binding Domain ◽  
Community Based

Abstract In a community-based sample of seropositive adults (n = 1101), we found that seropositive individuals who lived with a known coronavirus disease 2019 (COVID-19) case exhibited higher blood anti–severe acute respiratory syndrome coronavirus 2 spike receptor-binding domain immunoglobulin G concentrations and greater symptom severity compared to seropositive individuals who did not live with a known COVID-19 case.

scholarly journals Antibodies to the SARS-CoV-2 receptor-binding domain that maximize breadth and resistance to viral escape

2021 ◽  
Author(s):  
Tyler N Starr ◽  
Nadine Czudnochowski ◽  
Fabrizia Zatta ◽  
Young-Jun Park ◽  
Zhuoming Liu ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Binding Domain ◽  
Viral Escape ◽  
Binding Motif ◽  
Receptor Binding Domain ◽  
Viral Neutralization ◽  
Parental Antibody

An ideal anti-SARS-CoV-2 antibody would resist viral escape, have activity against diverse SARS-related coronaviruses, and be highly protective through viral neutralization and effector functions. Understanding how these properties relate to each other and vary across epitopes would aid development of antibody therapeutics and guide vaccine design. Here, we comprehensively characterize escape, breadth, and potency across a panel of SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD), including S309, the parental antibody of the late-stage clinical antibody VIR-7831. We observe a tradeoff between SARS-CoV-2 in vitro neutralization potency and breadth of binding across SARS-related coronaviruses. Nevertheless, we identify several neutralizing antibodies with exceptional breadth and resistance to escape, including a new antibody (S2H97) that binds with high affinity to all SARS-related coronavirus clades via a unique RBD epitope centered on residue E516. S2H97 and other escape-resistant antibodies have high binding affinity and target functionally constrained RBD residues. We find that antibodies targeting the ACE2 receptor binding motif (RBM) typically have poor breadth and are readily escaped by mutations despite high neutralization potency, but we identify one potent RBM antibody (S2E12) with breadth across sarbecoviruses closely related to SARS-CoV-2 and with a high barrier to viral escape. These data highlight functional diversity among antibodies targeting the RBD and identify epitopes and features to prioritize for antibody and vaccine development against the current and potential future pandemics.

scholarly journals Vaccine monitoring shows that focused immunization with SARS-CoV-2 receptor-binding domain provides a better neutralizing antibody response than full-length spike protein

2021 ◽  
Author(s):  
Rafael Bayarri-Olmos ◽  
Manja Idorn ◽  
Anne Rosbjerg ◽  
Laura Pérez-Alós ◽  
Cecilie Hansen ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Neutralization Test ◽  
Neutralizing Antibody ◽  
Binding Domain ◽  
Full Length ◽  
Receptor Binding Domain ◽  
Vaccine Response ◽  
Viral Neutralization ◽  
Neutralization Capacity

Abstract Effective tools to monitor SARS-CoV-2 transmission and humoral immune responses are highly needed. Protective humoral immunity involves neutralizing antibodies and will be a hallmark for the evaluation of a vaccine response efficacy. Here we present a sensitive, fast and simple neutralization ELISA method to determine the levels of antibody-mediated virus neutralization. We can show that it is strongly correlated with the more elaborate plaque reduction neutralization test (PRNT) (ρ = 0.9231, p < 0.0001). Furthermore, we present pre-clinical vaccine models using recombinant receptor binding domain (RBD) and full-length spike antigen as immunogens showing a profound antibody neutralization capacity that exceeds the highest neutralization titers from convalescent individuals. Using a panel of novel high-affinity murine monoclonal antibodies (mAbs) we also show that majority of the RBD-raised mAbs have inhibitory properties while only a few of the spike-raised mAbs do. In conclusion, the ELISA-based viral neutralization test offers a time- and cost-effective alternative to the PRNT. The immunization results indicate that vaccine strategies focused only on the RBD region may have major advantages over those based on the full spike sequence.

scholarly journals Comparative analyses of SARS-CoV-2 binding (IgG, IgM, IgA) and neutralizing antibodies from human serum samples

2020 ◽  
Author(s):  
Livia Mazzini ◽  
Donata Martinuzzi ◽  
Inesa Hyseni ◽  
Giulia Lapini ◽  
Linda Benincasa ◽  
...  
Keyword(s):  
Human Serum ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Binding Domain ◽  
Spike Protein ◽  
Wild Type Virus ◽  
Receptor Binding Domain ◽  
Serum Samples ◽  
Neutralization Titer ◽  
Human Serum Samples

ABSTRACTA newly identified coronavirus, named SARS-CoV-2, emerged in December 2019 in Hubei Province, China, and quickly spread throughout the world; so far, it has caused more than 18 million cases of disease and 700,000 deaths. The diagnosis of SARS-CoV-2 infection is currently based on the detection of viral RNA in nasopharyngeal swabs by means of molecular-based assays, such as real-time RT-PCR. Furthermore, serological assays aimed at detecting different classes of antibodies constitute the best surveillance strategy for gathering information on the humoral immune response to infection and the spread of the virus through the population, in order to evaluate the immunogenicity of novel future vaccines and medicines for the treatment and prevention of COVID-19 disease. The aim of this study was to determine SARS-CoV-2-specific antibodies in human serum samples by means of different commercial and in-house ELISA kits, in order to evaluate and compare their results first with one another and then with those yielded by functional assays using wild-type virus. It is important to know the level of SARS-CoV-2-specific IgM, IgG and IgA antibodies in order to predict population immunity and possible cross-reactivity with other coronaviruses and to identify potentially infectious subjects. In addition, in a small sub-group of samples, we performed a subtyping Immunoglobulin G ELISA. Our data showed an excellent statistical correlation between the neutralization titer and the IgG, IgM and IgA ELISA response against the receptor-binding domain of the spike protein, confirming that antibodies against this portion of the virus spike protein are highly neutralizing and that the ELISA Receptor-Binding Domain-based assay can be used as a valid surrogate for the neutralization assay in laboratories which do not have Biosecurity level-3 facilities.

scholarly journals Stereotypic neutralizing VH antibodies against SARS-CoV-2 spike protein receptor binding domain in COVID-19 patients and healthy individuals

2021 ◽  
pp. eabd6990
Author(s):  
Sang Il Kim ◽  
Jinsung Noh ◽  
Sujeong Kim ◽  
Younggeun Choi ◽  
Duck Kyun Yoo ◽  
...  
Keyword(s):  
B Cells ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
De Novo ◽  
Binding Domain ◽  
Host Cells ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Healthy Individuals

Stereotypic antibody clonotypes exist in healthy individuals and may provide protective immunity against viral infections by neutralization. We observed that 13 out of 17 patients with COVID-19 had stereotypic variable heavy chain (VH) antibody clonotypes directed against the receptor-binding domain (RBD) of SARS-CoV-2 spike protein. These antibody clonotypes were comprised of immunoglobulin heavy variable (IGHV)3-53 or IGHV3-66 and immunoglobulin heavy joining (IGHJ)6 genes. These clonotypes included IgM, IgG3, IgG1, IgA1, IgG2, and IgA2 subtypes and had minimal somatic mutations, which suggested swift class switching after SARS-CoV-2 infection. The different immunoglobulin heavy variable chains were paired with diverse light chains resulting in binding to the RBD of SARS-CoV-2 spike protein. Human antibodies specific for the RBD can neutralize SARS-CoV-2 by inhibiting entry into host cells. We observed that one of these stereotypic neutralizing antibodies could inhibit viral replication in vitro using a clinical isolate of SARS-CoV-2. We also found that these VH clonotypes existed in six out of 10 healthy individuals, with IgM isotypes predominating. These findings suggest that stereotypic clonotypes can develop de novo from naïve B cells and not from memory B cells established from prior exposure to similar viruses. The expeditious and stereotypic expansion of these clonotypes may have occurred in patients infected with SARS-CoV-2 because they were already present.

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