scholarly journals Longitudinal analysis of the humoral response to SARS-CoV-2 spike RBD in convalescent plasma donors

2020 ◽  
Author(s):  
Josée Perreault ◽  
Tony Tremblay ◽  
Marie-Josée Fournier ◽  
Mathieu Drouin ◽  
Guillaume Beaudoin-Bussières ◽  
...  
Keyword(s):  
Longitudinal Analysis ◽  
Plasma Cells ◽  
De Novo ◽  
Disease Onset ◽  
Humoral Response ◽  
Spike Protein ◽  
Strongly Correlated ◽  
Receptor Binding Domain ◽  
Specific Antibodies ◽  
Plasma Collection

ABSTRACTHéma-Québec, the blood supplier in the Province of Quebec, Canada, collects and tests convalescent plasma used in a clinical trial to determine the clinical efficacy of this product for the treatment of hospitalized COVID-19 patients. So far, we have collected 1159 plasma units from 282 COVID-19 convalescent donors. The presence of antibodies to the receptor binding domain (RBD) of SARS-CoV-2 spike protein in convalescent donors was established at the first donation. Seropositive donors were asked to donate additional plasma units every six days. Until now, 15 donors have donated at least four times and, in some cases, up to nine times. This allowed us to perform a longitudinal analysis of the persistence of SARS-CoV-2 RBD-specific antibodies in these repeat donors, with the first donation occurring 33-77 days after symptoms onset and donations up to 71-114 days after symptoms onset thereafter. In all donors, the level of antibodies remained relatively stable up to about 76 days after symptoms onset but then started to decrease more rapidly to reach, in some convalescent donors, a seronegative status within 100-110 days after symptoms onset. The decline in anti-RBD antibodies was not related to the number of donations but strongly correlated with the numbers of days after symptoms onset (r = 0.821). This suggests that de novo secretion of SARS-CoV-2 RBD antibodies by short-lived plasma cells stopped about 2-3 months after disease onset, an observation that has important implications for convalescent plasma collection and seroprevalence studies undertaken several months after the peak of infection.

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.

scholarly journals Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals

2020 ◽  
Author(s):  
Davide F. Robbiani ◽  
Christian Gaebler ◽  
Frauke Muecksch ◽  
Julio C. C. Lorenzi ◽  
Zijun Wang ◽  
...  
Keyword(s):  
Virus Entry ◽  
Protein S ◽  
Memory B Cells ◽  
Antibody Responses ◽  
Spike Protein ◽  
Human Antibody ◽  
Receptor Binding Domain ◽  
Single Digit ◽  
Specific Antibodies ◽  
Specific Memory

AbstractDuring the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-21–5. Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal neutralizing titers ranging from undetectable in 33% to below 1:1000 in 79%, while only 1% showed titers >1:5000. Antibody cloning revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titers, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC50s) as low as single digit ng/mL. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.

scholarly journals RBD-Fc-based COVID-19 vaccine candidate induces highly potent SARS-CoV-2 neutralizing antibody response

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Zezhong Liu ◽  
Wei Xu ◽  
Shuai Xia ◽  
Chenjian Gu ◽  
Xinling Wang ◽  
...  
Keyword(s):  
Subunit Vaccine ◽  
Vaccine Candidate ◽  
High Titer ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Angiotensin Converting Enzyme 2 ◽  
Specific Antibodies ◽  
Good Potential ◽  
Neutralizing Epitopes

AbstractThe pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed serious threats to global health and economy, thus calling for the development of safe and effective vaccines. The receptor-binding domain (RBD) in the spike protein of SARS-CoV-2 is responsible for its binding to angiotensin-converting enzyme 2 (ACE2) receptor. It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines. Here, we showed that immunization of mice with a candidate subunit vaccine consisting of SARS-CoV-2 RBD and Fc fragment of human IgG, as an immunopotentiator, elicited high titer of RBD-specific antibodies with robust neutralizing activity against both pseudotyped and live SARS-CoV-2 infections. The mouse antisera could also effectively neutralize infection by pseudotyped SARS-CoV-2 with several natural mutations in RBD and the IgG extracted from the mouse antisera could also show neutralization against pseudotyped SARS-CoV and SARS-related coronavirus (SARSr-CoV). Vaccination of human ACE2 transgenic mice with RBD-Fc could effectively protect mice from the SARS-CoV-2 challenge. These results suggest that SARS-CoV-2 RBD-Fc has good potential to be further developed as an effective and broad-spectrum vaccine to prevent infection of the current SARS-CoV-2 and its mutants, as well as future emerging SARSr-CoVs and re-emerging SARS-CoV.

Design and Synthesis of De Novo Boomerang Shaped Molecules and their In Silico & SERS-based Interactions with SARS-CoV-2 Spike Protein and ACE2

2021 ◽  
Author(s):  
Amrutham Linet ◽  
Manu M Joseph ◽  
Haritha Mambatta ◽  
Shamna k ◽  
Sunil varughese ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
In Silico ◽  
De Novo ◽  
Binding Domain ◽  
Spike Protein ◽  
Epithelial Tissue ◽  
Receptor Binding Domain ◽  
Design And Synthesis ◽  
Recent Outbreak

The recent outbreak of the COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which infects human epithelial tissue by interaction of the receptor-binding domain of its spike...

scholarly journals The duration and specificity of the humoral immune response to SARS-CoV-2

2021 ◽  
pp. 7-12
Author(s):  
E. I. Dubrovskyi ◽  
B. V. Dons’koi
Keyword(s):  
Immune Response ◽  
Quality Control ◽  
Humoral Response ◽  
Threshold Value ◽  
Spike Protein ◽  
Obstetrics And Gynecology ◽  
Study Group ◽  
Specific Antibodies ◽  
Humoral Immune ◽  
Pcr Test

Background. Our assumption that immunity after COVID-19 will persist has been fully confirmed in the researches already conducted. Our work is a continuation of research that demonstrates the results obtained 12 months of determining the humoral response in patients after COVID-19. Materials and methods. The research involved 42 individuals. All subjects had a positive PCR test for COVID-19. At certain intervals, from 40 to 240 days, individuals in the group were tested for IgG SARS-CoV-2. The last step was to check the level of IgG to the COVID-19 nucleocapsid and spike protein in the research group for 360 days from the onset of the disease. A private certified laboratory in Kyiv, the “DNA Laboratory”, was involved. Patients were tested for antibodies to COVID-19 by ELISA using serology COVID-19 test systems VitroTest (Ukraine). The immunological laboratory of the Institute of Pediatrics, Obstetrics and Gynecology was used in parallel for interlaboratory quality control. The results of the research coincided. Results. The level of class G immunoglobulins to nucleocapsid in the subjects has gradually decreased over 8 months. It is noteworthy that in the period from 40 to 150 days in all 42 patients (100 %) antibodies did not disappear. Decreasing of antibodies occurred between 150 and 240 days. However, the data obtained for 360 days significantly changed the picture. In a certain part of the subjects, who had low or even negative levels of antibodies for 8 months, as of 12 months, the level of immunoglobulin (Ig) class G again rose above the threshold value. Thus, we see that from the group of 42 people 92.8 % have positive antibodies to the nucleocapsid, and 7.2 %. Conclusions. The data obtained illustrate that in the study group within 12 months after SARS-CoV-2, the vast majority of individuals remain with specific antibodies to the nucleocapsid and spike-protein.

scholarly journals SARS-CoV-2–Specific Antibody Detection for Seroepidemiology: A Multiplex Analysis Approach Accounting for Accurate Seroprevalence

2020 ◽  
Vol 222 (9) ◽  
pp. 1452-1461 ◽  
Author(s):  
Gerco den Hartog ◽  
Rutger M Schepp ◽  
Marjan Kuijer ◽  
Corine GeurtsvanKessel ◽  
Josine van Beek ◽  
...  
Keyword(s):  
Multiplex Assay ◽  
Spike Protein ◽  
Antibody Detection ◽  
Receptor Binding Domain ◽  
Test Results ◽  
Protein Subunits ◽  
Specific Antibodies ◽  
Single Antigen ◽  
Specific Igg ◽  
Kinetics Of

Abstract Background The COVID-19 pandemic necessitates better understanding of the kinetics of antibody production induced by infection with SARS-CoV-2. We aimed to develop a high-throughput multiplex assay to detect antibodies to SARS-CoV-2 to assess immunity to the virus in the general population. Methods Spike protein subunits S1 and receptor binding domain, and nucleoprotein were coupled to microspheres. Sera collected before emergence of SARS-CoV-2 (n = 224) and of non-SARS-CoV-2 influenza-like illness (n = 184), and laboratory-confirmed cases of SARS-CoV-2 infection (n = 115) with various severities of COVID-19 were tested for SARS-CoV-2–specific IgG concentrations. Results Our assay discriminated SARS-CoV-2–induced antibodies and those induced by other viruses. The assay specificity was 95.1%–99.0% with sensitivity 83.6%–95.7%. By merging the test results for all 3 antigens a specificity of 100% was achieved with a sensitivity of at least 90%. Hospitalized COVID-19 patients developed higher IgG concentrations and the rate of IgG production increased faster compared to nonhospitalized cases. Conclusions The bead-based serological assay for quantitation of SARS-CoV-2–specific antibodies proved to be robust and can be conducted in many laboratories. We demonstrated that testing of antibodies against multiple antigens increases sensitivity and specificity compared to single-antigen–specific IgG determination.

scholarly journals The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients

2020 ◽  
Vol 5 (48) ◽  
pp. eabc8413 ◽  
Author(s):  
Lakshmanane Premkumar ◽  
Bruno Segovia-Chumbez ◽  
Ramesh Jadi ◽  
David R. Martinez ◽  
Rajendra Raut ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Clinical Symptoms ◽  
Severe Disease ◽  
Population Level ◽  
Respiratory Illness ◽  
Binding Domain ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Specific Antibodies

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that first emerged in late 2019 is responsible for a pandemic of severe respiratory illness. People infected with this highly contagious virus can present with clinically inapparent, mild, or severe disease. Currently, the virus infection in individuals and at the population level is being monitored by PCR testing of symptomatic patients for the presence of viral RNA. There is an urgent need for SARS-CoV-2 serologic tests to identify all infected individuals, irrespective of clinical symptoms, to conduct surveillance and implement strategies to contain spread. As the receptor binding domain (RBD) of the spike protein is poorly conserved between SARS-CoVs and other pathogenic human coronaviruses, the RBD represents a promising antigen for detecting CoV-specific antibodies in people. Here we use a large panel of human sera (63 SARS-CoV-2 patients and 71 control subjects) and hyperimmune sera from animals exposed to zoonotic CoVs to evaluate RBD's performance as an antigen for reliable detection of SARS-CoV-2-specific antibodies. By day 9 after the onset of symptoms, the recombinant SARS-CoV-2 RBD antigen was highly sensitive (98%) and specific (100%) for antibodies induced by SARS-CoVs. We observed a strong correlation between levels of RBD binding antibodies and SARS-CoV-2 neutralizing antibodies in patients. Our results, which reveal the early kinetics of SARS-CoV-2 antibody responses, support using the RBD antigen in serological diagnostic assays and RBD-specific antibody levels as a correlate of SARS-CoV-2 neutralizing antibodies in people.

scholarly journals Emerging New Approaches in Desensitization: Targeted Therapies for HLA Sensitization

2021 ◽  
Vol 12 ◽  
Author(s):  
Ashley Y. Choi ◽  
Miriam Manook ◽  
Danae Olaso ◽  
Brian Ezekian ◽  
Jaeberm Park ◽  
...  
Keyword(s):  
Plasma Cells ◽  
De Novo ◽  
Humoral Response ◽  
Therapeutic Interventions ◽  
Humoral Immune ◽  
Antibody Mediated Rejection ◽  
Multiple Components ◽  
Improved Outcomes ◽  
Allograft Loss

There is an urgent need for therapeutic interventions for desensitization and antibody-mediated rejection (AMR) in sensitized patients with preformed or de novo donor-specific HLA antibodies (DSA). The risk of AMR and allograft loss in sensitized patients is increased due to preformed DSA detected at time of transplant or the reactivation of HLA memory after transplantation, causing acute and chronic AMR. Alternatively, de novo DSA that develops post-transplant due to inadequate immunosuppression and again may lead to acute and chronic AMR or even allograft loss. Circulating antibody, the final product of the humoral immune response, has been the primary target of desensitization and AMR treatment. However, in many cases these protocols fail to achieve efficient removal of all DSA and long-term outcomes of patients with persistent DSA are far worse when compared to non-sensitized patients. We believe that targeting multiple components of humoral immunity will lead to improved outcomes for such patients. In this review, we will briefly discuss conventional desensitization methods targeting antibody or B cell removal and then present a mechanistically designed desensitization regimen targeting plasma cells and the humoral response.

scholarly journals Early Humoral Response Correlates with Disease Severity and Outcomes in COVID-19 Patients

2020 ◽  
Author(s):  
Anwar M Hashem ◽  
Abdullah Algaissi ◽  
Sarah A Almahboub ◽  
Mohamed A Alfaleh ◽  
Turki S Abujamel ◽  
...  
Keyword(s):  
Disease Severity ◽  
Neutralizing Antibodies ◽  
Disease Onset ◽  
Humoral Response ◽  
High Morbidity ◽  
Strongly Correlated ◽  
Time Period ◽  
Clinical Presentations ◽  
Almost All ◽  
Kinetics Of

The Coronavirus Disease 2019 (COVID-19), caused by the novel SARS-CoV-2, continues to spread globally with significantly high morbidity and mortality rates. Immunological surrogate markers, in particular antigen-specific responses, are of unquestionable value for clinical management of patients with COVID-19. Here, we investigated the kinetics of IgM, IgG against the spike (S) and nucleoproteins (N) proteins and their neutralizing capabilities in hospitalized patients with RT-PCR confirmed COVID-19 infection. Our data show that SARS-CoV-2 specific IgG, IgM and neutralizing antibodies (nAbs) were readily detectable in almost all COVID-19 patients with various clinical presentations. Notably, anti-S and -N IgG, peaked 20-40 day after disease onset, and were still detectable for at least up to 70 days, with nAbs observed during the same time period. Moreover, nAbs titers were strongly correlated with IgG antibodies. Significantly higher levels of nAbs as well as anti-S1 and N IgG and IgM antibodies were found in patients with more severe clinical presentations, patients requiring admission to intensive care units (ICU) or those with fatal outcomes. Interestingly, lower levels of antibodies, particularly anti-N IgG and IgM in the first 15 days after symptoms onset, were found in survivors and those with mild clinical presentations. Collectively, these findings provide new insights into the characteristics and kinetics of antibody responses in COVID-19 patients with different disease severity.

scholarly journals The recombinant subunit vaccine RBD-Fc, consisting of SARS-CoV-2 RBD and human IgG Fc as an immunopotentiator, elicits robust neutralizing antibody responses against SARS-CoV-2 infection

2020 ◽  
Author(s):  
Zezhong Liu ◽  
Wei Xu ◽  
Shuai Xia ◽  
Chenjian Gu ◽  
Xinling Wang ◽  
...  
Keyword(s):  
Subunit Vaccine ◽  
High Titer ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Human Igg ◽  
Specific Antibodies ◽  
Good Potential ◽  
Neutralizing Epitopes

Abstract The pandemic of COVID-19 caused by SARS-CoV-2 has posed serious threats to global health and economy, thus calling for the development of safe and effective vaccines. The receptor-binding domain (RBD) in the spike protein of SARS-CoV-2 is responsible for its binding to ACE2 receptor. It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines. Here, we showed that immunization of mice with a candidate subunit vaccine consisting of SARS-CoV-2 RBD and Fc fragment of human IgG, as an immunopotentiator, elicited high titer of RBD-specific antibodies with robust neutralizing activity against both pseudotyped and live SARS-CoV-2 infections. The mouse antisera could also effectively neutralize infection by pseudotyped SARS-CoV-2 with several natural mutations in RBD and the IgG extracted from the mouse antisera could also show neutralization against pseudotyped SARS-CoV and SARS-related coronavirus (SARSr-CoV). Vaccination of human ACE2 transgenic mice with RBD-Fc could effectively protect mice from the SARS-CoV-2 challenge. These results suggest that SARS-CoV-2 RBD-Fc has good potential to be further developed as an effective and broad-spectrum vaccine to prevent infection of the current SARS-CoV-2 and its mutants, as well as future emerging SARSr-CoVs and re-emerging SARS-CoV.

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