Coronavirus Spike Protein Research Articles

Comparison of Six Immunoassays for Assaying Levels of Immunoglobulin G against the Nucleocapsid and Spike Proteins of SARS-CoV-2

Introduction: Assay kits for detection of Immunoglobulin G (IgG) against the nucleocapsid protein (anti-nucleocapsid IgG) and spike proteins (anti-spike IgG) of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) were commercially provided by several manufacturers. These assay kits should be verified by measuring the same sample. Aim: To compare the diagnostic value of three Coronavirus Disease-2019 (COVID-19) kits in evaluating six immunoassays developed by three manufacturers (Abbott, Euglena, and Roche) to detect anti-nucleocapsid IgG and anti-spike IgG. Materials and Methods: Present study was an observational cross-sectional study conducted from June 2020 to December 2020. Antibody titers for anti-nucleocapsid IgG and anti-spike IgG among 429 Healthcare Workers (HCWs) in a Tone Central Hospital, Japan where a nosocomial infection of the COVID19 occurred were measured by six immunoassays with kits developed by three different manufacturers. The sensitivity and specificity of each kit was compared to real-time Reverse Transcription-Polymerase Chain Reaction (RT-qPCR). Results: Six of the HCWs tested positive for SARS-CoV-2 via RT-qPCR, and the rest tested negative. The severity of COVID19 among these six HCWs ranged from mild to moderate. The sensitivity and specificity values against RT-qPCR were, 100% and 99.5% for Abbott, 83.3% and 100% for Euglena, and 100% and 100% for Roche when using the nucleocapsid protein assay and 100% and 99.8% for Abbott, 100% and 100% for Euglena, and 100% and 100% for Roche when using the spike protein assay kit. Conclusion: The commercial kits provided by three manufacturers reflected the immune status of individuals. There were no major differences in the performance of these test kits. Discordant results with the antibody titer for anti-nucleocapsid IgG and anti-spike IgG were detected by using assay kits provided by Abbott and Euglena. To evaluate the past history of COVID-19, it should be noted that the single measurement of anit-nucleocapsid IgG or anti-spike IgG could not exclude false negative or positives.

In silico screening and characterization of novel natural peptides as spike protein inhibitors of novel coronavirus (severe acute respiratory syndrome coronavirus 2)

BACKGROUND: The present work is a computational approach to discover the novel peptides that can interact and inhibit the action of spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MATERIALS AND METHODS: A total of 193 numbers probable naturally occurring antiviral peptides were retrieved from the antimicrobial database. The three-dimensional structure of all the peptides was predicted by the Chimera tool followed by energy minimization. Similarly, the spike protein of SARS-CoV-2 chain A (PDB ID 6VBY) structure was obtained from the Protein Data Bank (PDB) and used as the receptor. RESULTS: Protein–protein docking was performed for all the peptides followed by some screening criteria that resulted in three numbers of potential peptides such as CAP11 binds to a receptor-binding domain (RBD), mytilin B to S1/S2 cleavage regions, and mBD-1 as N-terminal-binding domain of spike protein. Further screening and evaluation of solubility and the toxic properties of the peptides it was obtained that the peptide molecules CAP11 and mytilin B are nontoxic. Further, the RBD-binding nature of CAP11 peptide was evaluated comparatively by taking the human ACE2 protein and RBD region of the wild-type SARS-CoV-2, triple mutant, South African mutant (B.1.351), by using molecular docking followed by interface analysis. It was predicted that the CAP11 peptide was able to bind perfectly with the RBD domain of both wild type and triple mutant one but not to the South African mutant.

Novel Sensing Algorithm for Linear Read-Out of Bimodal Waveguide Interferometric Biosensors

Biosensors employing photonics integrated circuits, and specifically those that rely on interferometric evanescent wave working principles, have outstanding performances due to the extreme sensitivity exhibited in one-step and direct assay, without the need of amplification. Within the interferometric configurations, the Bimodal Waveguide (BiMW) interferometric sensor stands out due to its demonstrated sensitivity for real-life applications and the simplicity of its design. To overcome the ambiguities that arise from the periodic nature of interferometric read-outs, a new all-optical modulation and the subsequent trigonometry-based algorithm have been proposed and applied to the BiMW biosensor. This new algorithm has been successfully employed for the selective identification and quantification of the external Spike (S) protein of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Our biosensing results from this simple, quick, and user-friendly method demonstrate high sensitivity and specificity and pave the way towards a point-of-care device for general use.

Identification of antigens recognized by salivary IgA using microbial protein microarrays.

Secretory IgA plays an important role in the mucosal immune system for protection against pathogens. However, the antigens recognized by these antibodies have only been partially studied. We comprehensively investigated the antigens bound by salivary IgA in healthy adults using microbial protein microarrays. This confirmed that saliva contained IgA antibodies that bind to a variety of pathogenic microorganisms, including spike proteins of severe acute respiratory syndrome coronavirus 2, severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus, and other human coronavirus species. Also, many subtypes and strains of influenza virus were bound, regardless of the seasonal or vaccine strains. Salivary IgA also bound many serogroups and serovars of Escherichia coli and Salmonella. Taken together, these findings suggest that salivary IgA, which exhibits broad reactivity, is likely an essential element of the mucosal immune system at the forefront of defense against infection.

A study on the demographic, clinical, and radiological profile of lineage B.1.1.7 (United Kingdom) strain Covid-19 patients at Telangana institute of medical sciences and research, Hyderabad

Background: Emergence of variants with specific mutations in key epitopes in the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) raises concerns pertinent to its severity. Aims and Objectives: To assess the demographics, clinico-radiological pattern, and outcome of reverse transcription-polymerase chain reaction (RT-PCR) positive isolated coronavirus disease 2019 (COVID-19) patients arrived from the United Kingdom (UK). Materials and Methods: A cross-sectional, observational study was conducted in RT-PCR positive COVID-19 patients arrived from the UK, from December 2020 to February 2021. Nasopharyngeal samples of all patients were sent for whole-genome sequencing of SARS-CoV-2. The aimed parameters were compared between the B.1.17 positive and non-B.1.1.7 groups, among the people, arrived from the UK. All statistical tests with P<0.05 were considered significant. Results: A total of 59 SARS-CoV2 infected patients, who arrived from the UK, were isolated from December 2020 to February 2021 at Telangana Institute of Medical Sciences hospital, Hyderabad, were enrolled in the study. Of these, 27 patients (mean age-31.81±11.28 years) were infected with the B.1.1.7, diagnosed by whole genomic sequencing. Males were predominant in our study. Personal habits such as smoking, alcohol intake were higher among the sequenced group with a significant P<0.05. The most common symptoms observed in the sequenced group were cough (22.22%), sore throat (22.22%), cold (11.11%), fever (11.11%), and in the unsequenced group were cough (22.22%), cold (6.25%), fever (6.25%). In the sequenced group, chest X-ray posteroanterior view was normal in 74%, patchy ground-glass opacities was observed in 25.92% patients, whereas in the unsequenced group it was 84.37% and 15.62%, respectively. Asymptomatic patients, observed in the sequenced and unsequenced group were 48.18% and 78.12%, respectively, and symptomatic patients were 51.85% and 21.87%, respectively. We found a statistically significant difference between sequenced and unsequenced patients in the asymptomatic group with a significant P<0.05. In the sequenced and unsequenced group, mild cases were 48.18% and 18.75%, moderate cases were 3.7% and 3.12%, respectively. We found no evidence of an association between disease severity and lineage B.1.17. Conclusion: Our data, within the context and limitations of a real-world study, provide initial reassurance that severity in hospitalized patients with B.1.1.7 is not markedly different from severity in those without B.1.1.7.

A systematic study on the binding affinity of SARS-CoV-2 spike protein to antibodies.

The COVID-19 pandemic has caused a worldwide health crisis and economic recession. Effective prevention and treatment methods are urgently required to control the pandemic. However, the emergence of novel SARS-CoV-2 variants challenges the effectiveness of currently available vaccines and therapeutic antibodies. In this study, through the assessment of binding free energies, we analyzed the mutational effects on the binding affinity of the coronavirus spike protein to neutralizing antibodies, patient-derived antibodies, and artificially designed antibody mimics. We designed a scoring method to assess the immune evasion ability of viral variants. We also evaluated the differences between several targeting sites on the spike protein of antibodies. The results presented herein might prove helpful in the development of more effective therapies in the future.

Corrigendum to "Development of SARS-CoV-2 Inhibitors Using Molecular Docking Study with Different Coronavirus Spike Protein and ACE2” [J Mol Docking. 2021;1(2):1-14

Authors have found an error in the previous version (Shamkh, IM, & Pratiwi, D. (2021). Development of SARS-CoV-2 Inhibitors Using Molecular Docking Study with Different Coronavirus Spike Protein and ACE2. Journal of Molecular Docking, 1(1), 1-14. https://doi.org/10.33084/jmd.v1i1.2212), of which Dr. Hanaa S. Omar as supervisor of the research, is not listed as one of the authors. In this note, Dr. Hanaa S. Omar was added as one of the authors, with the status of the corresponding author in the study.

Spike protein of SARS-COV-2 as a potential target for phytochemical constituents: A literature review

SARS-CoV-2 belongs to well-known SARS Coronaviridae family. One of the main structural proteins of SARS-CoV-2 is the spike protein that is present around the surface of a viral cell and plays an essential role in viral attachment, fusion and invasion in host cell. Once a virus invades a cell, it replicates and infects other cells. The fundamental role of spike protein in the progression of viral infection has led to an increased interest in exploring agents that target the viral spike protein for effective control of CoVID-19. The related data from published articles reviewed and numerous phytochemicals that reportedly target the spike proteins of coronaviruses by computational studies briefly discussed. These active constituents possess the potential to develop as therapeutic and antiviral agents against SARS-CoV-2.

Covalent coupling of HIV-1 glycoprotein trimers to biodegradable calcium phosphate nanoparticles via genetically encoded aldehyde-tags

The usage of antigen-functionalized nanoparticles has become a major focus in the field of experimental HIV-1 vaccine research during the last decade. Various molecular mechanisms to couple native-like trimers of the HIV-1 envelope protein (Env) onto nanoparticle surfaces have been reported, but many come with disadvantages regarding the coupling efficiency and stability. In this study, a short amino acid sequence (“aldehyde-tag”) was introduced at the C-terminus of a conformationally stabilized native-like Env. The post-translational conversion of a tag-associated cysteine to formylglycine creates a site-specific aldehyde group without alteration of the Env antigenicity. This aldehyde group was further utilized for bioconjugation of Env trimers. We demonstrated that the low acidic environment necessary for this bioconjugation is not affecting the trimer conformation. Furthermore, we developed a two-step coupling method for pH-sensitive nanoparticles. To this end, we conjugated aldehyde-tagged Env with Propargyl-PEG3-aminooxy linker (oxime ligation; Step-one) and coupled these conjugates by copper-catalyzed azide-alkyne cycloaddition (Click reaction; Step-two) to calcium phosphate nanoparticles (CaPs) functionalized with terminal azide groups. CaPs displaying orthogonally arranged Env trimers on their surface (o-CaPs) were superior in activation of Env-specific B-cells (in vitro) and induction of Env-specific antibody responses (in vivo) compared to CaPs with Env trimers coupled in a randomly oriented manner. Taken together, we present a reliable method for the site-specific, covalent coupling of HIV-1 Env native-like trimers to the surface of nanoparticle delivery systems. This method can be broadly applied for functionalization of nanoparticle platforms with conformationally stabilized candidate antigens for both vaccination and diagnostic approaches. Statement of significanceDuring the last decade antigen-functionalized nanoparticles have become a major focus in the field of experimental HIV-1 vaccines. Rational design led to the production of conformationally stabilized HIV-1 envelope protein (Env) trimers - the only target for the humoral immune system. Various molecular mechanisms to couple Env trimers onto nanoparticle surfaces have been reported, but many come with disadvantages regarding the coupling efficiency and stability. In this paper, we describe a highly selective bio-conjugation of Env trimers to the surface of medically relevant calcium phosphate nanoparticles. This method maintains the native-like protein conformation and has a broad potential application in functionalization of nanoparticle platforms with stabilized candidate antigens (including stabilized spike proteins of coronaviruses) for both vaccination and diagnostic approaches.

In silico evidence of beauvericin antiviral activity against SARS-CoV-2

BackgroundScientists are still battling severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus 2019 (COVID-19) pandemic so human lives can be saved worldwide. Secondary fungal metabolites are of intense interest due to their broad range of pharmaceutical properties. Beauvericin (BEA) is a secondary metabolite produced by the fungus Beauveria bassiana. Although promising anti-viral activity has previously been reported for BEA, studies investigating its therapeutic potential are limited. MethodsThe objective of this study was to assess the potential usage of BEA as an anti-viral molecule via protein–protein docking approaches using MolSoft. ResultsIn-silico results revealed relatively favorable binding energies for BEA to different viral proteins implicated in the vital life stages of this virus. Of particular interest is the capability of BEA to dock to both the main coronavirus protease (Pockets A and B) and spike proteins. These results were validated by molecular dynamic simulation (Gromacs). Several parameters, such as root-mean-square deviation/fluctuation, the radius of gyration, H-bonding, and free binding energy were analyzed. Computational analyses revealed that interaction of BEA with the main protease pockets in addition to the spike glycoprotein remained stable. ConclusionAltogether, our results suggest that BEA might be considered as a potential competitive and allosteric agonist inhibitor with therapeutic options for treating COVID-19 pending in vitro and in vivo validation.

Identification of a Novel Neutralizing Epitope on the N-Terminal Domain of the Human Coronavirus 229E Spike Protein.

The receptor binding domain (RBD) of the coronavirus spike protein (S) has been verified to be the main target for potent neutralizing antibodies (nAbs) in most coronaviruses, and the N-terminal domain (NTD) of some betacoronaviruses has also been indicated to induce nAbs. For alphacoronavirus HCoV-229E, its RBD has been shown to have neutralizing epitopes, and these epitopes could change over time. However, whether neutralizing epitopes exist on the NTD and whether these epitopes change like those of the RBD are still unknown. Here, we verified that neutralizing epitopes exist on the NTD of HCoV-229E. Furthermore, we characterized an NTD targeting nAb 5H10, which could neutralize both pseudotyped and authentic HCoV-229E VR740 in vitro. Epitope mapping indicated that 5H10 targeted motif E1 (147-167 aa) and identified F159 as critical for 5H10 binding. More importantly, our results revealed that motif E1 was highly conserved among clinical isolates except for F159. Further data proved that mutations at position 159 gradually appeared over time and could completely abolish the neutralizing ability of 5H10, supporting the notion that position 159 may be under selective pressure during the human epidemic. In addition, we also found that contemporary clinical serum has a stronger binding capacity for the NTD of contemporary strains than historic strains, proving that the epitope on the NTD could change over time. In summary, these findings define a novel neutralizing epitope on the NTD of HCoV-229E S and provide a theoretical basis for the design of vaccines against HCoV-229E or related coronaviruses. IMPORTANCE Characterization of the neutralizing epitope of the spike (S) protein, the major invasion protein of coronaviruses, can help us better understand the evolutionary characteristics of these viruses and promote vaccine development. To date, the neutralizing epitope distribution of alphacoronaviruses is not well known. Here, we identified a neutralizing antibody that targeted the N-terminal domain (NTD) of the alphacoronavirus HCoV-229E S protein. Epitope mapping revealed a novel epitope that was not previously discovered in HCoV-229E. Further studies identified an important residue, F159. Mutations that gradually appeared over time at this site abolished the neutralizing ability of 5H10, indicating that selective pressure occurred at this position in the spread of HCoV-229E. Furthermore, we found that the epitopes within the NTD also changed over time. Taken together, our findings defined a novel neutralizing epitope and highlighted the role of the NTD in the future prevention and control of HCoV-229E or related coronaviruses.

December 2021 Pulmonary Case of the Month: Interstitial Lung Disease with Red Knuckles

No abstract available. Article truncated after 150 words. We thought a follow-up to our original brief review of COVID-19 in February, 2020 might be useful. As we write this in early December 2021, we again caution that this area is rapidly changing and what is true today will likely be outdated tomorrow. We again borrowed heavily from the Centers for Disease Control (CDC) CDC website and the NIH website which have extensive discussions over numerous pages covering COVID-19. Our hope is to condense those recommendations. We do not discuss inpatient care in any detail. COVID-19 Variants The initial steps of coronavirus infection involve the specific binding of the coronavirus spike (S) protein to the cellular entry receptors which are normally on a cell. These include human aminopeptidase N (APN; HCoV-229E), angiotensin-converting enzyme 2 (ACE2; HCoV-NL63, SARS-CoV and SARS-CoV-2) and dipeptidyl peptidase 4 (DPP4; MERS-CoV). All viruses, but especially simple single-stranded RNA viruses like COVID-19, constantly change through mutation …

Preparation for the challenge of heavily mutated Omicron variant.

Preparation for the challenge of heavily mutated Omicron variant.

A novel multiplex electrochemiluminescent immunoassay for detection and quantification of anti-SARS-CoV-2 IgG and anti-seasonal endemic human coronavirus IgG.

BackgroundMultiplex immunoassays capture a comprehensive profile of the humoral response against SARS-CoV-2 and human endemic coronaviruses. We validated a multiplex panel (V-PLEX Panel 2) from Meso Scale Diagnostics targeting antibodies against nine coronavirus antigens. Performance was compared against alternative single- and multi-antigen immunoassays.MethodsSera collected for clinical or public health testing from 2018 to 2020 (n = 135) were used to compare all tested platforms, and inter-test agreement was assessed by Cohen's kappa coefficient. Sample category (positive/negative) was assigned based on collection date relative to the index case in Canada, and SARS-CoV-2 PCR and serology results. 117 out of the 135 samples (31 positive, 86 negative) were assigned a category and were used to calculate sensitivity and specificity, with MSD's test results based upon manufacturer-set cut-offs.ResultsWe observed SARS-CoV-2 target sensitivities of 100% and specificities >94% for all antigens (RBD, Nucleocapsid, Spike) in V-PLEX Panel 2. When targets were combined, we found a SARS-CoV-2 sensitivity of 100% and specificity of 98.8% with no difference in performance compared to clinical assays, and Cohen's kappa ranging from 0.798 to 0.945 compared to surface plasmon resonance imaging (SPRi). Quantitative measurements of antibodies against the Spike protein of endemic human coronaviruses were concordant with SPRi.ConclusionMeso Scale Diagnostics’ V-PLEX Coronavirus Panel 2 allows for highly sensitive and specific detection of anti-coronavirus IgG, and is concordant with other serological assays for detection of antibodies against SARS-CoV-2 and the endemic human coronaviruses, making it a good tool for humoral response characterization after both infection and vaccination.

Oral Administration of Coronavirus Spike Protein Provides Protection to Newborn Pigs When Challenged with PEDV.

To investigate whether oral administration of maize-produced S antigen can provide passive immunity to piglets against porcine epidemic diarrhea virus (PEDV), 16 pregnant sows were randomly assigned to one of four treatments: (1) injection of PEDV vaccine (INJ), (2) maize grain without S protein (CON), (3) maize grain containing low dose of S antigen (LOV) and (4) maize grain containing a high dose of S antigen (HOV). Vaccines were administered on days 57, 85 and 110 of gestation. Sows’ serum and colostrum were collected at farrowing and milk on day 6 post-challenge to quantify neutralizing antibodies (NABs) and cytokines. Piglets were challenged with PEDV 3–5 d after farrowing, and severity of disease and mortality assessed on day 11 post-challenge. Disease severity was lower in LOV and INJ compared with HOV and CON, whereas the survival rate increased in piglets from LOV sows compared with HOV and CON (p ≤ 0.001). Higher titers of NABs and lower levels of cytokine granulocyte-macrophage colony-stimulating factor in sows’ milk were positively correlated with piglet survivability (p ≤ 0.05). These data suggest that feeding S protein in corn to pregnant sows protects nursing piglets against PEDV.

Biocomputational Analysis of Selected Compounds against Spike Protein: A Bioinformatics Approach

The main objective of the current study is to check the effectiveness of selected phytocompounds from the Chinese origin plant Cotinus coggygria in inhibiting the spike protein of Corona virus by assaying in the pharmacological tools and molecular docking analysis. Cotinus coggygria is a shrub which belongs to the family Anacardiaceae. The various phytochemicals of this compound shows the antiviral properties and some of the effective ones 3D structure was retrieved from PubChem and chemspider databases. The retrieved sequence was subjected to various bioinformatics tools such as SwissADME, PyRx, and Autodock for the molecular docking to check the effectiveness of selected phytocompounds in degrading the Spike protein of Corona virus. The results from the ADME and Autodock has proved the selected phytochemicals to have an antiviral property which is beneficial and effective against the Spike protein of Corona virus. Although Cotinus coggygria is known to show a medicinal property and is also being used as traditional medicine in various country, it has now been the spotlight for many researchers. The phytocompounds considered for this study has shown a better results in degrading the spike protein.

Waning of Anti-spike Antibodies in AZD1222 (ChAdOx1) Vaccinated Healthcare Providers: A Prospective Longitudinal Study.

IntroductionCoronavirus disease 2019 (COVID-19) vaccines are nothing short of a miracle story halting the pandemic across the globe. Nearly half of the global population has received at least one dose. Nevertheless, antibody levels in vaccinated people have shown waning, and breakthrough infections have occurred. Our study aims to measure antibody kinetics following AZD1222 (ChAdOx1) vaccination six months after the second dose and the factors affecting the kinetics.Materials and methodsWe conducted a prospective longitudinal study monitoring for six months after the second of two AZD1222 (ChAdOx1) vaccine doses in healthcare professionals and healthcare facility employees at Veer Surendra Sai Institute of Medical Sciences and Research (included doctors, nurses, paramedical staff, security and sanitary workers, and students). Two 0.5-mL doses of the vaccine were administered intramuscularly, containing 5 x 1010 viral particles 28 to 30 days between doses. We collected blood samples one month after the first dose (Round 1), one month after the second dose (Round 2), and six months after the second dose (Round 3). We tested for immunoglobulin G (IgG) levels against the receptor-binding domain of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by chemiluminescence microparticle immunoassay. We conducted a linear mixed model analysis to study the antibody kinetics and influencing factors.ResultsOur study included 122 participants (mean age, 41.5 years; 66 men, 56 women). The geometric mean IgG titers were 138.01 binding antibody units (BAU)/mL in Round 1, 176.48 BAU/mL in Round 2, and 112.95 BAU/mL in Round 3. Seven participants showed seroreversion, and 11 had breakthrough infections. Eighty-six participants showed a substantial decline in antibody titer from Rounds 2 to 3. Persons aged 45 or older had higher mean titer than people aged younger than 45 years. Overweight and obese (BMI ≥ 25 kg/m2) had a higher mean titer than average or underweight persons. The only significant predictor of IgG titers at six months was SARS-CoV-2 infection on mixed model analysis.ConclusionWe found a substantial decline in antibody levels leading to seven cases of seroreversion in healthcare professionals who received the ChAdOx1 vaccine. History of prior COVID-19 was the only significant factor in antibody levels at six months. Seroreversion and breakthrough infection warrant further research into the optimal timing and potential benefits of booster doses of the AZD1222 (ChAdOx1) COVID-19 vaccine.

Life Sciences Discovery and Technology Highlights

Life Sciences Discovery and Technology Highlights

Cross-reactive antibodies after SARS-CoV-2 infection and vaccination.

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.

SARS-CoV-2-Reactive Mucosal B Cells in the Upper Respiratory Tract of Uninfected Individuals.

SARS-CoV-2 is a respiratory pathogen that can cause severe disease in at-risk populations but results in asymptomatic infections or a mild course of disease in the majority of cases. We report the identification of SARS-CoV-2-reactive B cells in human tonsillar tissue obtained from children who were negative for coronavirus disease 2019 prior to the pandemic and the generation of mAbs recognizing the SARS-CoV-2 Spike protein from these B cells. These Abs showed reduced binding to Spike proteins of SARS-CoV-2 variants and did not recognize Spike proteins of endemic coronaviruses, but subsets reacted with commensal microbiota and exhibited SARS-CoV-2-neutralizing potential. Our study demonstrates pre-existing SARS-CoV-2-reactive Abs in various B cell populations in the upper respiratory tract lymphoid tissue that may lead to the rapid engagement of the pathogen and contribute to prevent manifestations of symptomatic or severe disease.