Receptor-binding domain of SARS-CoV-2 contribution to the neutrophil activation during 100 nm particle-induced immune response in conduction airway mucosa of mice

2021 ◽  
Vol 21 (3) ◽  
pp. 97-102
Author(s):  
Elena L. Bolkhovitina ◽  
Julia D. Vavilova ◽  
Andrey O. Bogorodskiy ◽  
Ivan S. Okhrimenko ◽  
Valentin I. Borshchevskiy ◽  
...  
Keyword(s):  
Immune Response ◽  
Receptor Binding ◽  
Neutrophil Migration ◽  
Three Dimensional ◽  
Binding Domain ◽  
Strategy Development ◽  
Receptor Binding Domain ◽  
Phagocytic Cells ◽  
Conducting Airway ◽  
Airway Mucosa

BACKGROUND: Airborne pathogens such as virus particles undergo elimination from the respiratory tract by mucociliary clearance and phagocytosis by immune cells. The data about phagocytic cell type infiltration and stimuli that attract phagocytic cells to conducting airway are required for the anti-virus immune response mechanism understanding and the treatment strategy development. AIM: To detect the role of the receptor-binding domain of SARS-CoV-2 in neutrophil immune response activation in conducting airway mucosa after 100 nm particles application. MATERIALS AND METHODS: C57BL/6 mice received an oropharyngeal application of fluorescent 100 nm particles suspended in the receptor-binding domain of SARS-CoV-2 solution. 24 hours after, conducting airways of mice were dissected and subjected for immunohistochemistry as whole-mounts. Three-dimensional images of conducting airway regions were obtained using confocal microscopy. Quantitative image analysis was performed to estimate the ingestion activity of neutrophils in conducting airway mucosa. RESULTS: Neutrophil migration to conducting airway mucosa was detected in case of the application of particles in receptor-binding domain solution, but not in phosphate buffer or bovine serum albumin solution. Receptor-binding domain solution alone also induced neutrophil migration to conducting airway mucosa. Infiltrating conducting airway wall mucosa neutrophils contributed to particles internalization. CONCLUSIONS: The receptor-binding domain of SARS-CoV-2 can activate the neutrophil-mediated response in conducting airway mucosa.

scholarly journals Recombinant Mycobacterium paragordonae Expressing SARS-CoV-2 Receptor-Binding Domain as a Vaccine Candidate Against SARS-CoV-2 Infections

2021 ◽  
Vol 12 ◽  
Author(s):  
Byoung-Jun Kim ◽  
Hyein Jeong ◽  
Hyejun Seo ◽  
Mi-Hyun Lee ◽  
Hyun Mu Shin ◽  
...  
Keyword(s):  
Immune Response ◽  
Single Dose ◽  
Immune Responses ◽  
Receptor Binding ◽  
Humoral Immune Response ◽  
Vaccine Candidate ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Live Virus ◽  
Humoral Immune

At present, concerns that the recent global emergence of SARS-CoV-2 variants could compromise the current vaccines have been raised, highlighting the urgent demand for new vaccines capable of eliciting T cell-mediated immune responses, as well as B cell-mediated neutralizing antibody production. In this study, we developed a novel recombinant Mycobacterium paragordonae expressing the SARS-CoV-2 receptor-binding domain (RBD) (rMpg-RBD-7) that is capable of eliciting RBD-specific immune responses in vaccinated mice. The potential use of rMpg-RBD-7 as a vaccine for SARS-CoV-2 infections was evaluated in in vivo using mouse models of two different modules, one for single-dose vaccination and the other for two-dose vaccination. In a single-dose vaccination model, we found that rMpg-RBD-7 versus a heat-killed strain could exert an enhanced cell-mediated immune (CMI) response, as well as a humoral immune response capable of neutralizing the RBD and ACE2 interaction. In a two-dose vaccination model, rMpg-RBD-7 in a two-dose vaccination could also exert a stronger CMI and humoral immune response to neutralize SARS-CoV-2 infections in pseudoviral or live virus infection systems, compared to single dose vaccinations of rMpg-RBD or two-dose RBD protein immunization. In conclusion, our data showed that rMpg-RBD-7 can lead to an enhanced CMI response and humoral immune responses in mice vaccinated with both single- or two-dose vaccination, highlighting its feasibility as a novel vaccine candidate for SARS-CoV-2. To the best of our knowledge, this study is the first in which mycobacteria is used as a delivery system for a SARS-CoV-2 vaccine.

scholarly journals Three-dimensional reconstructions of the bacteriophage CUS-3 virion reveal a conserved coat protein I-domain but a distinct tailspike receptor-binding domain

Virology ◽  
2014 ◽  
Vol 464-465 ◽  
pp. 55-66 ◽  
Author(s):  
Kristin N. Parent ◽  
Jinghua Tang ◽  
Giovanni Cardone ◽  
Eddie B. Gilcrease ◽  
Mandy E. Janssen ◽  
...  
Keyword(s):  
Coat Protein ◽  
Receptor Binding ◽  
Three Dimensional ◽  
Binding Domain ◽  
Receptor Binding Domain

scholarly journals Immunogenicity Studies of Plant-Produced SARS-CoV-2 Receptor Binding Domain-Based Subunit Vaccine Candidate with Different Adjuvant Formulations

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 744
Author(s):  
Konlavat Siriwattananon ◽  
Suwimon Manopwisedjaroen ◽  
Balamurugan Shanmugaraj ◽  
Eakachai Prompetchara ◽  
Chutitorn Ketloy ◽  
...  
Keyword(s):  
Immune Response ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Lipid A ◽  
Binding Domain ◽  
Poly I:C ◽  
Receptor Binding Domain ◽  
Monophosphoryl Lipid A ◽  
Polycytidylic Acid ◽  
Significant Difference

Due to the rapid transmission of the coronavirus disease 2019 (COVID-19) causing serious public health problems and economic burden, the development of effective vaccines is a high priority for controlling the virus spread. Our group has previously demonstrated that the plant-produced receptor-binding domain (RBD) of SARS-CoV-2 fused with Fc of human IgG was capable of eliciting potent neutralizing antibody and cellular immune responses in animal studies, and the immunogenicity could be improved by the addition of an alum adjuvant. Here, we performed a head-to-head comparison of different commercially available adjuvants, including aluminum hydroxide gel (alum), AddaVax (MF59), monophosphoryl lipid A from Salmonella minnesota R595 (mPLA-SM), and polyinosinic-polycytidylic acid (poly(I:C)), in mice by combining them with plant-produced RBD-Fc, and the differences in the immunogenicity of RBD-Fc with different adjuvants were evaluated. The specific antibody responses in terms of total IgG, IgG1, and IgG2a subtypes and neutralizing antibodies, as well as vaccine-specific T-lymphocyte responses, induced by the different tested adjuvants were compared. We observed that all adjuvants tested here induced a high level of total IgG and neutralizing antibodies, but mPLA-SM and poly (I:C) showed the induction of a balanced IgG1 and IgG2a (Th2/Th1) immune response. Further, poly (I:C) significantly increased the frequency of IFN-γ-expressing cells compared with control, whereas no significant difference was observed between the adjuvanted groups. This data revealed the adjuvants’ role in enhancing the immune response of RBD-Fc vaccination and the immune profiles elicited by different adjuvants, which could prove helpful for the rational development of next-generation SARS-CoV-2 RBD-Fc subunit vaccines. However, additional research is essential to further investigate the efficacy and safety of this vaccine formulation before clinical trials.

scholarly journals Comparative Immunomodulatory Evaluation of the Receptor Binding Domain of the SARS-CoV-2 Spike Protein; a Potential Vaccine Candidate Which Imparts Potent Humoral and Th1 Type Immune Response in a Mouse Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Tripti Shrivastava ◽  
Balwant Singh ◽  
Zaigham Abbas Rizvi ◽  
Rohit Verma ◽  
Sandeep Goswami ◽  
...  
Keyword(s):  
Immune Response ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Unmet Need ◽  
Binding Domain ◽  
Spike Protein ◽  
Cell Immune Response ◽  
Receptor Binding Domain

The newly emerged novel coronavirus, SARS-CoV-2, the causative agent of COVID-19 has proven to be a threat to the human race globally, thus, vaccine development against SARS-CoV-2 is an unmet need driving mass vaccination efforts. The receptor binding domain of the spike protein of this coronavirus has multiple neutralizing epitopes and is associated with viral entry. Here we have designed and characterized the SARS-CoV-2 spike protein fragment 330-526 as receptor binding domain 330-526 (RBD330-526) with two native glycosylation sites (N331 and N343); as a potential subunit vaccine candidate. We initially characterized RBD330-526 biochemically and investigated its thermal stability, humoral and T cell immune response of various RBD protein formulations (with or without adjuvant) to evaluate the inherent immunogenicity and immunomodulatory effect. Our result showed that the purified RBD immunogen is stable up to 72 h, without any apparent loss in affinity or specificity of interaction with the ACE2 receptor. Upon immunization in mice, RBD generates a high titer humoral response, elevated IFN-γ producing CD4+ cells, cytotoxic T cells, and robust neutralizing antibodies against live SARS-CoV-2 virus. Our results collectively support the potential of RBD330-526 as a promising vaccine candidate against SARS-CoV-2.

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 A compromised specific humoral immune response against the SARS-CoV-2 receptor-binding domain is related to viral persistence and periodic shedding in the gastrointestinal tract

2020 ◽  
Vol 17 (11) ◽  
pp. 1119-1125 ◽  
Author(s):  
Fengyu Hu ◽  
Fengjuan Chen ◽  
Zhihua Ou ◽  
Qinghong Fan ◽  
Xinghua Tan ◽  
...  
Keyword(s):  
Immune Response ◽  
Gastrointestinal Tract ◽  
Receptor Binding ◽  
Humoral Immune Response ◽  
Clinical Manifestations ◽  
Viral Persistence ◽  
Binding Domain ◽  
Health Concern ◽  
Receptor Binding Domain ◽  
Humoral Immune

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been redetected after discharge in some coronavirus disease 2019 (COVID-19) patients. The reason for the recurrent positivity of the test and the potential public health concern due to this occurrence are still unknown. Here, we analyzed the viral data and clinical manifestations of 289 domestic Chinese COVID-19 patients and found that 21 individuals (7.3%) were readmitted for hospitalization after detection of SARS-CoV-2 after discharge. First, we experimentally confirmed that the virus was involved in the initial infection and was not a secondary infection. In positive retests, the virus was usually found in anal samples (15 of 21, 71.4%). Through analysis of the intracellular viral subgenomic messenger RNA (sgmRNA), we verified that positive retest patients had active viral replication in their gastrointestinal tracts (3 of 16 patients, 18.7%) but not in their respiratory tracts. Then, we found that viral persistence was not associated with high viral titers, delayed viral clearance, old age, or more severe clinical symptoms during the first hospitalization. In contrast, viral rebound was associated with significantly lower levels of and slower generation of viral receptor-binding domain (RBD)-specific IgA and IgG antibodies. Our study demonstrated that the positive retest patients failed to create a robust protective humoral immune response, which might result in SARS-CoV-2 persistence in the gastrointestinal tract and possibly in active viral shedding. Further exploration of the mechanism underlying the rebound in SARS-CoV-2 in this population will be crucial for preventing virus spread and developing effective vaccines.

scholarly journals Differential serological and neutralizing antibody dynamics after an infection by a single SARS-CoV-2 strain

2020 ◽  
Author(s):  
Emmanuelle Billon-Denis ◽  
Audrey Ferrier-Rembert ◽  
Annabelle Garnier ◽  
Laurence Cheutin ◽  
Clarisse Vigne ◽  
...  
Keyword(s):  
Immune Response ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Binding Domain ◽  
Clinical Severity ◽  
Individual Factors ◽  
Receptor Binding Domain ◽  
Antibody Titers ◽  
Antibody Dynamics

Abstract BackgroundWe report here the case of two coworkers infected by the same SARS-CoV-2 strain, presenting two different immunological outcomes. CaseOne patient presented a strong IgG anti-receptor-binding domain immune response correlated with a low and rapidly decreasing titer of neutralizing antibodies. The other patient had similar strong IgG anti-receptor-binding domain immune response but high neutralizing antibody titers. Discussion and ConclusionThus, host individual factors may be the main drivers of the immune response varying with age and clinical severity.

Sign in / Sign up

Export Citation Format

Share Document