scholarly journals Cross-reactive antibodies after SARS-CoV-2 infection and vaccination

2021 ◽  
Author(s):  
Marloes Grobben ◽  
Karlijn van der Straten ◽  
Philip J.M. Brouwer ◽  
Mitch Brinkkemper ◽  
Pauline Maisonnasse ◽  
...  
Keyword(s):  
Fold Increase ◽  
Cross Reactivity ◽  
S Protein ◽  
Healthy Donors ◽  
Main Target ◽  
Protein Immunization ◽  
Human Coronaviruses ◽  
Novel Coronavirus ◽  
S Proteins

Current SARS-CoV-2 vaccines are losing efficacy against emerging variants and may not protect against future novel coronavirus outbreaks, emphasizing the need for more broadly protective vaccines. To inform the development of a pan-coronavirus vaccine, we investigated the presence and specificity of cross-reactive antibodies against the spike (S) proteins of human coronaviruses (hCoV) after SARS-CoV-2 infection and vaccination. We found an 11 to 123-fold increase in antibodies binding to SARS-CoV and MERS-CoV as well as a 2 to 4-fold difference in antibodies binding to seasonal hCoVs in COVID-19 convalescent sera compared to pre-pandemic healthy donors, with the S2 subdomain of the S protein being the main target for cross-reactivity. In addition, we detected cross-reactive antibodies to all hCoV S proteins after SARS-CoV-2 S protein immunization in macaques, with higher responses for hCoV more closely related to SARS-CoV-2. These findings support the feasibility of and provide guidance for development of a pan-coronavirus vaccine.

scholarly journals Cross-reactive antibodies after SARS-CoV-2 infection and vaccination

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Marloes Grobben ◽  
Karlijn van der Straten ◽  
Philip JM Brouwer ◽  
Mitch Brinkkemper ◽  
Pauline Maisonnasse ◽  
...  
Keyword(s):  
Fold Increase ◽  
Cross Reactivity ◽  
S Protein ◽  
Healthy Donors ◽  
Main Target ◽  
Human Coronaviruses ◽  
Novel Coronavirus ◽  
S Proteins

Current SARS-CoV-2 vaccines are losing efficacy against emerging variants and may not protect against future novel coronavirus outbreaks, emphasizing the need for more broadly protective vaccines. To inform the development of a pan-coronavirus vaccine, we investigated the presence and specificity of cross-reactive antibodies against the spike (S) proteins of human coronaviruses (hCoV) after SARS-CoV-2 infection and vaccination. We found an 11- to 123-fold increase in antibodies binding to SARS-CoV and MERS-CoV as well as a 2- to 4-fold difference in antibodies binding to seasonal hCoVs in COVID-19 convalescent sera compared to pre-pandemic healthy donors, with the S2 subdomain of the S protein being the main target for cross-reactivity. In addition, we detected cross-reactive antibodies to all hCoV S proteins after SARS-CoV-2 vaccination in macaques and humans, with higher responses for hCoV more closely related to SARS-CoV-2. These findings support the feasibility of and provide guidance for development of a pan-coronavirus vaccine.

scholarly journals Distinct Structural Flexibility within SARS-CoV-2 Spike Protein Reveals Potential Therapeutic Targets

2020 ◽  
Author(s):  
Serena H. Chen ◽  
M. Todd Young ◽  
John Gounley ◽  
Christopher Stanley ◽  
Debsindhu Bhowmik
Keyword(s):  
Host Cells ◽  
Dynamics Simulation ◽  
Structural Flexibility ◽  
The Novel ◽  
Simulation Approach ◽  
S Protein ◽  
Therapeutic Development ◽  
Human Coronaviruses ◽  
Novel Coronavirus ◽  
S Proteins

AbstractThe emergence and rapid worldwide spread of the novel coronavirus disease, COVID-19, has prompted concerted efforts to find successful treatments. The causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), uses its spike (S) protein to gain entry into host cells. Therefore, the S protein presents a viable target to develop a directed therapy. Here, we deployed an integrated artificial intelligence with molecular dynamics simulation approach to provide new details of the S protein structure. Based on a comprehensive structural analysis of S proteins from SARS-CoV-2 and previous human coronaviruses, we found that the protomer state of S proteins is structurally flexible. Without the presence of a stabilizing beta sheet from another protomer chain, two regions in the S2 domain and the hinge connecting the S1 and S2 subunits lose their secondary structures. Interestingly, the region in the S2 domain was previously identified as an immunodominant site in the SARS-CoV-1 S protein. We anticipate that the molecular details elucidated here will assist in effective therapeutic development for COVID-19.

scholarly journals Immunologic testing for SARS-CoV-2 infection from the antigen perspective

2020 ◽  
pp. JCM.02160-20
Author(s):  
Dandan Li ◽  
Jinming Li
Keyword(s):  
Cross Reactivity ◽  
Diagnostic Methods ◽  
Clinical Samples ◽  
Serological Testing ◽  
S Protein ◽  
N Protein ◽  
Viral Loads ◽  
Improved Performance ◽  
Human Coronaviruses ◽  
Novel Coronavirus

Coronavirus disease 2019 (COVID-19) caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally as a severe pandemic. SARS-CoV-2 infection stimulates antigen-specific antibody responses. Multiple serologic tests have been developed for SARS-CoV-2. However, which antigens are most suitable for serological testing remains poorly understood. Specifically, which antigens have the highest sensitivity and specificity for serological testing and which have the least cross-reactivity with other coronaviruses are currently unknown. Previous studies have shown that the S1 domain of the spike (S) protein has very low cross-reactivity between epidemic coronaviruses and common human coronaviruses, whereas the S2 domain of the S protein, and the nucleocapsid protein (N protein) show low-level cross-reactivity. Therefore, S1 is considered more specific than the native homotrimer of the S protein, and the receptor-binding domain as an antigen to test patient antibodies is more sensitive than the native N protein. In addition, an increasing number of studies have used multi-antigen protein arrays to screen serum from convalescent patients with COVID-19. Antigen combinations demonstrated improved performance as compared to each individual antigen. For rapid antigen detection, the sensitivity of the test is higher in the first week of onset of the disease with high viral loads. Highly sensitive and specific immunological diagnostic methods for antibodies or those that directly detect viral antigens in clinical samples would be beneficial for the rapid and accurate diagnosis of SARS-CoV-2 infection.

scholarly journals Monoclonal antibodies for the S2 subunit of spike of SARS-CoV-1 cross-react with the newly-emerged SARS-CoV-2

2020 ◽  
Vol 25 (28) ◽  
Author(s):  
Zhiqiang Zheng ◽  
Vanessa Marthe Monteil ◽  
Sebastian Maurer-Stroh ◽  
Chow Wenn Yew ◽  
Carol Leong ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Common Cold ◽  
Sandwich Elisa ◽  
Cell Receptor ◽  
Cross Reactivity ◽  
S Protein ◽  
Mammalian Cell Lines ◽  
Infected Cells ◽  
The Cross ◽  
Novel Coronavirus

Background A novel coronavirus, SARS-CoV-2, which emerged at the end of 2019 and causes COVID-19, has resulted in worldwide human infections. While genetically distinct, SARS-CoV-1, the aetiological agent responsible for an outbreak of severe acute respiratory syndrome (SARS) in 2002–2003, utilises the same host cell receptor as SARS-CoV-2 for entry: angiotensin-converting enzyme 2 (ACE2). Parts of the SARS-CoV-1 spike glycoprotein (S protein), which interacts with ACE2, appear conserved in SARS-CoV-2. Aim The cross-reactivity with SARS-CoV-2 of monoclonal antibodies (mAbs) previously generated against the S protein of SARS-CoV-1 was assessed. Methods The SARS-CoV-2 S protein sequence was aligned to those of SARS-CoV-1, Middle East respiratory syndrome (MERS) and common-cold coronaviruses. Abilities of mAbs generated against SARS-CoV-1 S protein to bind SARS-CoV-2 or its S protein were tested with SARS-CoV-2 infected cells as well as cells expressing either the full length protein or a fragment of its S2 subunit. Quantitative ELISA was also performed to compare binding of mAbs to recombinant S protein. Results An immunogenic domain in the S2 subunit of SARS-CoV-1 S protein is highly conserved in SARS-CoV-2 but not in MERS and human common-cold coronaviruses. Four murine mAbs raised against this immunogenic fragment could recognise SARS-CoV-2 S protein expressed in mammalian cell lines. In particular, mAb 1A9 was demonstrated to detect S protein in SARS-CoV-2-infected cells and is suitable for use in a sandwich ELISA format. Conclusion The cross-reactive mAbs may serve as useful tools for SARS-CoV-2 research and for the development of diagnostic assays for COVID-19.

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

2020 ◽  
Author(s):  
Yuanmei Zhu ◽  
Danwei Yu ◽  
Yang Han ◽  
Hongxia Yan ◽  
Huihui Chong ◽  
...  
Keyword(s):  
Public Health ◽  
Receptor Binding ◽  
Cross Reactivity ◽  
Social Stability ◽  
Receptor Binding Domain ◽  
Serum Antibodies ◽  
Serum Samples ◽  
S Protein ◽  
Palm Civet ◽  
Novel Coronavirus

AbstractThe current COVID-19 pandemic, caused by a novel coronavirus SARS-CoV-2, poses serious threats to public health and social stability, calling for urgent need for vaccines and therapeutics. SARS-CoV-2 is genetically close to SARS-CoV, thus it is important to define the between antigenic cross-reactivity and neutralization. In this study, we firstly analyzed 20 convalescent serum samples collected from SARS-CoV infected individuals 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. Multiple panels of antisera from mice and rabbits immunized with a full-length S and RBD immunogens of SARS-CoV were also characterized, verifying the cross-reactive neutralization against SARS-CoV-2. Interestingly, we found that a palm civet SARS-CoV-derived RBD elicited more potent cross-neutralizing responses in immunized animals than the RBD from a human SARS-CoV strain, informing a strategy to develop a universe vaccine against emerging CoVs.SummarySerum antibodies from SARS-CoV infected patients and immunized animals cross-neutralize SARS-CoV-2 suggests strategies for universe vaccines against emerging CoVs.

scholarly journals Systematic evaluation of SARS-CoV-2 spike protein derived peptides for diagnosis of COVID-19 patients

2020 ◽  
Author(s):  
Yang Li ◽  
Danyun Lai ◽  
Qing Lei ◽  
Zhaowei Xu ◽  
Hongyan Hou ◽  
...  
Keyword(s):  
Serological Test ◽  
Protein S ◽  
Cross Reactivity ◽  
Spike Protein ◽  
Systematic Evaluation ◽  
Peptide Microarray ◽  
Serological Tests ◽  
S Protein ◽  
Asymptomatic Patients ◽  
Human Coronaviruses

Serological test plays an essential role in monitoring and combating COVID-19 pandemic. Recombinant spike protein (S protein), especially S1 protein is one of the major reagents for serological tests. However, the high cost in production of S protein, and the possible cross-reactivity with other human coronaviruses poses unneglectable challenges. Taking advantage of a peptide microarray of full spike protein coverage, we analyzed 2,434 sera from 858 COVID-19 patients, sera from 63 asymptomatic patients and 610 controls collected from multiple clinical centers. Based on the results of the peptide microarray, we identified several S protein derived 12-mer peptides that have high diagnosis performance. Particularly, for monitoring IgG response, one peptide (aa 1148-1159 or S2-78) has a comparable sensitivity (95.5%, 95% CI 93.7-96.9%) and specificity (96.7%, 95% CI 94.8-98.0%) to that of S1 protein for detection of both COVID-19 patients and asymptomatic infections. Furthermore, the performance of S2-78 IgG for diagnosis was successfully validated by ELISA with an independent sample cohort. By combining S2-78/ S1 with other peptides, a two-step strategy was proposed to ensure both the sensitivity and specificity of S protein based serological assay. The peptide/s identified in this study could be applied independently or in combination with S1 protein for accurate, affordable, and accessible COVID-19 diagnosis.

scholarly journals Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein

2020 ◽  
Author(s):  
Seth J. Zost ◽  
Pavlo Gilchuk ◽  
Rita E. Chen ◽  
James Brett Case ◽  
Joseph X. Reidy ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Cross Reactivity ◽  
The Novel ◽  
Receptor Binding Domain ◽  
Human Monoclonal Antibodies ◽  
S Protein ◽  
Global Pandemic ◽  
Antibody Discovery ◽  
Novel Coronavirus ◽  
Rapid Antibody

Antibodies are a principal determinant of immunity for most RNA viruses and have promise to reduce infection or disease during major epidemics. The novel coronavirus SARS-CoV-2 has caused a global pandemic with millions of infections and hundreds of thousands of deaths to date1,2. In response, we used a rapid antibody discovery platform to isolate hundreds of human monoclonal antibodies (mAbs) against the SARS-CoV-2 spike (S) protein. We stratify these mAbs into five major classes based on their reactivity to subdomains of S protein as well as their cross-reactivity to SARS-CoV. Many of these mAbs inhibit infection of authentic SARS-CoV-2 virus, with most neutralizing mAbs recognizing the receptor-binding domain (RBD) of S. This work defines sites of vulnerability on SARS-CoV-2 S and demonstrates the speed and robustness of new antibody discovery methodologies.

scholarly journals Immune response dynamics in COVID-19 patients to SARS-CoV-2 and other human coronaviruses

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254367
Author(s):  
Resmi Ravindran ◽  
Cindy McReynolds ◽  
Jun Yang ◽  
Bruce D. Hammock ◽  
Aamer Ikram ◽  
...  
Keyword(s):  
Serological Test ◽  
High Sensitivity ◽  
Cross Reactivity ◽  
Response Dynamics ◽  
S Protein ◽  
Infected People ◽  
N Protein ◽  
Patient Health ◽  
Antibody Titers ◽  
Human Coronaviruses

COVID-19 serological test must have high sensitivity as well as specificity to rule out cross-reactivity with common coronaviruses (HCoVs). We have developed a quantitative multiplex test, measuring antibodies against spike (S) proteins of SARS-CoV-2, SARS-CoV, MERS-CoV, and common human coronavirus strains (229E, NL63, OC43, HKU1), and nucleocapsid (N) protein of SARS-CoV viruses. Receptor binding domain of S protein of SARS-CoV-2 (S-RBD), and N protein, demonstrated sensitivity (94% and 92.5%, respectively) in COVID-19 patients (n = 53), with 98% specificity in non-COVID-19 respiratory-disease (n = 98), and healthy-controls (n = 129). Anti S-RBD and N antibodies appeared five to ten days post-onset of symptoms, peaking at approximately four weeks. The appearance of IgG and IgM coincided while IgG subtypes, IgG1 and IgG3 appeared soon after the total IgG; IgG2 and IgG4 remained undetectable. Several inflammatory cytokines/chemokines were found to be elevated in many COVID-19 patients (e.g., Eotaxin, Gro-α, CXCL-10 (IP-10), RANTES (CCL5), IL-2Rα, MCP-1, and SCGF-b); CXCL-10 was elevated in all. In contrast to antibody titers, levels of CXCL-10 decreased with the improvement in patient health suggesting it as a candidate for disease resolution. Importantly, anti-N antibodies appear before S-RBD and differentiate between vaccinated and infected people—current vaccines (and several in the pipeline) are S protein-based.

scholarly journals Antibody response patterns in COVID-19 patients with different levels of disease severity—Japan

2020 ◽  
Author(s):  
Kazuo Imai ◽  
Yutaro Kitagawa ◽  
Sakiko Tabata ◽  
Katsumi Kubota ◽  
Mayu Nagura-Ikeda ◽  
...  
Keyword(s):  
Antibody Response ◽  
Disease Severity ◽  
Cross Reactivity ◽  
Response Patterns ◽  
Igg Antibodies ◽  
Past Infection ◽  
Infection Pattern ◽  
Human Coronaviruses ◽  
Novel Coronavirus ◽  
Different Levels

AbstractBackgroundWe analyzed antibody response patterns according to level of disease severity in patients with novel coronavirus disease 2019 (COVID-19) in Japan.MethodsWe analyzed 611 serum specimens from 231 patients with COVID-19 (mild, 170; severe, 31; critical, 30). IgM and IgG antibodies against nucleocapsid protein (N) and spike 1 protein (S1) were detected by enzyme-linked immunosorbent assays.FindingsThe peaks of fitting curves for the OD values of IgM and IgG antibodies against N appeared simultaneously, while those against S1 were delayed compared with N. The OD values of IgM against N and IgG against both N and S1 were significantly higher in the severe and critical cases than in the mild cases at 11 days after symptom onset. The seroconversion rates of IgG were higher than those of IgM against both N and S1 during the clinical course based on the optimal cut-off values defined in this study. The seroconversion rates of IgG and IgM against N and S1 were higher in the severe and critical cases than in the mild cases.ConclusionOur findings show that a stronger antibody response occurred in COVID-19 patients with greater disease severity and there were low seroconversion rates of antibodies against N and S1 in the mild cases. The antibody response patterns in our population suggest a second infection pattern, leading us to hypothesize that cross-reactivity occurs between SARS-CoV-2 and past infection with other human coronaviruses.

scholarly journals Comparative Genomics of Receptor Binding Domains of Spike Protein and Receptor Interaction in COVID-19 Patient

2020 ◽  
Author(s):  
Rimjhim Dasgupta
Keyword(s):  
Receptor Binding ◽  
Binding Domain ◽  
Host Cells ◽  
Receptor Interaction ◽  
Receptor Binding Domain ◽  
Furin Cleavage ◽  
S Protein ◽  
Human Coronaviruses ◽  
Novel Coronavirus ◽  
Bat Coronavirus

The current outbreak of viral pneumonia in the city of Wuhan, China, was caused by a novel coronavirus designated 2019-nCoV, as determined by sequencing the viral RNA genome. Among its genome, S protein is surface-exposed and mediates entry into host cells. Currently it is one of the main targets for designing antibodies (Abs), therapeutic and vaccine. Earlier studies stated that ACE2 (angiotensin converting enzyme 2) could facilitate S protein mediated entry for this newly emerged coronavirus. Here we have taken an attempt to compare the genetic structure of receptor binding domain within S protein of highly pathogenic human coronaviruses (special reference to 2019-nCoV) with Bat coronavirus RaTG13. We have compared 2019-nCov receptor binding domain (RBD) with other pathogenic human coronaviruses (MERS-CoV and SARS-CoV) and Bat coronavirus RaTG13. We found that it is closest to RaTG13 RBD than MERS-CoV and SARS-CoV. Our study shows that 2019-nCov RBD also has significant identity with pangolin S protein RBD. We have also predicted the amino acid residues within RDB those may play important role for ACE2 receptor interaction. We identified unique signature for furin cleavage in 2019-nCov S protein but not in of other pathogenic human coronaviruses (tested here), bat coronavirus RaTG13 or pangolin.

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