scholarly journals Possible host-adaptation of SARS-CoV-2 due to improved ACE2 receptor binding in mink

2020 ◽  
Author(s):  
Matthijs R A Welkers ◽  
Alvin X Han ◽  
Chantal B E M Reusken ◽  
Dirk Eggink
Keyword(s):  
Immune Responses ◽  
Receptor Binding ◽  
Host Adaptation ◽  
Receptor Binding Domain ◽  
S Protein ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Protein Receptor ◽  
The Mean ◽  
Potential Adaptation

Abstract SARS-CoV-2 infections on mink farms are increasingly observed in several countries, leading to the massive culling of animals on affected farms. Recent studies showed multiple (anthropo)zoonotic transmission events between humans and mink on these farms. Mink-derived SARS-CoV-2 sequences from The Netherlands and Denmark contain multiple substitutions in the S protein receptor binding domain (RBD). Molecular modeling showed that these substitutions increase the mean binding energy, suggestive of potential adaptation of the SARS-CoV-2 S protein to the mink ACE2 receptor. These substitutions could possibly also impact human ACE2 binding affinity as well as humoral immune responses directed to the RBD region of the SARS-CoV-2 S protein in humans. We wish to highlight these observations to raise awareness and urge for the continued surveillance of mink (and other animal)-related infections.

scholarly journals Durability of SARS-CoV-2-specific IgG responses in saliva for up to 8 months after infection

2021 ◽  
Author(s):  
Pranay R. Randad ◽  
Nora Pisanic ◽  
Kate Kruczynski ◽  
Tyrone Howard ◽  
Magdielis Gregory Rivera ◽  
...  
Keyword(s):  
Immune Responses ◽  
Receptor Binding ◽  
Half Life ◽  
Large Scale ◽  
Receptor Binding Domain ◽  
Rt Pcr ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Population Immunity ◽  
Specific Igg

We evaluated the durability of IgG responses specific to SARS-CoV-2 nucleocapsid (N), receptor binding domain (RBD), and spike (S) antigens in saliva up to 8 months after RT-PCR-confirmed COVID-19 using a multiplex salivary assay. We estimated a half-life of 64 days (d) (95% CI: 49, 80 d) for N, 100 d for RBD (95% CI: 58, 141 d), and 148 d (95% CI: 62, 238 d) for S IgG responses in saliva, consistent with half-life estimates previously reported in blood. Saliva can serve as an alternative to blood to monitor humoral immune responses on a large scale following natural SARS-CoV-2 infection and vaccination for surveillance and assessment of population immunity.

scholarly journals Conjugation of Human β-Defensin 2 to Spike Protein Receptor-Binding Domain Induces Antigen-Specific Protective Immunity against Middle East Respiratory Syndrome Coronavirus Infection in Human Dipeptidyl Peptidase 4 Transgenic Mice

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 635
Author(s):  
Ju Kim ◽  
Ye Lin Yang ◽  
Yongsu Jeong ◽  
Yong-Suk Jang
Keyword(s):  
Middle East ◽  
Immune Responses ◽  
Receptor Binding ◽  
Dipeptidyl Peptidase ◽  
Binding Domain ◽  
Middle East Respiratory Syndrome ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Dipeptidyl Peptidase 4 ◽  
Protein Receptor

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe acute respiratory symptoms. Due to the lack of medical countermeasures, effective and safe vaccines against MERS-CoV infection are urgently required. Although different types of candidate vaccines have been developed, their immunogenicity is limited, and the dose and administration route need optimization to achieve optimal protection. We here investigated the potential use of human β-defensin 2 (HBD 2) as an adjuvant to enhance the protection provided by MERS-CoV vaccination. We found that immunization of human dipeptidyl peptidase 4 (hDPP4)-transgenic (hDPP4-Tg) mice with spike protein receptor-binding domain (S RBD) conjugated with HBD 2 (S RBD-HBD 2) induced potent antigen (Ag)-specific adaptive immune responses and protected against MERS-CoV infection. In addition, immunization with S RBD-HBD 2 alleviated progressive pulmonary fibrosis in the lungs of MERS-CoV-infected hDPP4-Tg mice and suppressed endoplasmic reticulum stress signaling activation upon viral infection. Compared to intramuscular administration, intranasal administration of S RBD-HBD 2 induced more potent mucosal IgA responses and was more effective for protecting against intranasal MERS-CoV infection. In conclusion, our findings suggest that HBD 2 potentiates Ag-specific immune responses against viral Ag and can be used as an adjuvant enhancing the immunogenicity of subunit vaccine candidates against MERS-CoV.

scholarly journals Structure-Based Stabilization of HIV-1 gp120 Enhances Humoral Immune Responses to the Induced Co-Receptor Binding Site

2009 ◽  
Vol 5 (5) ◽  
pp. e1000445 ◽  
Author(s):  
Barna Dey ◽  
Krisha Svehla ◽  
Ling Xu ◽  
Dianne Wycuff ◽  
Tongqing Zhou ◽  
...  
Keyword(s):  
Immune Responses ◽  
Binding Site ◽  
Receptor Binding ◽  
Receptor Binding Site ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Hiv 1

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 Roadmap to developing a recombinant coronavirus S protein receptor-binding domain vaccine for severe acute respiratory syndrome

2012 ◽  
Vol 11 (12) ◽  
pp. 1405-1413 ◽  
Author(s):  
Shibo Jiang ◽  
Maria Elena Bottazzi ◽  
Lanying Du ◽  
Sara Lustigman ◽  
Chien-Te Kent Tseng ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
S Protein ◽  
Protein Receptor

scholarly journals Structural Insights into Immune Recognition of the Severe Acute Respiratory Syndrome Coronavirus S Protein Receptor Binding Domain

2009 ◽  
Vol 388 (4) ◽  
pp. 815-823 ◽  
Author(s):  
John E. Pak ◽  
Chetna Sharon ◽  
Malathy Satkunarajah ◽  
Thierry C. Auperin ◽  
Cheryl M. Cameron ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Binding Domain ◽  
Immune Recognition ◽  
Receptor Binding Domain ◽  
S Protein ◽  
Protein Receptor ◽  
Structural Insights

scholarly journals SARS-CoV-2 Infection Is Asymptomatic in Nearly Half of Adults with Robust Anti-Spike Protein Receptor-Binding Domain Antibody Response

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 207
Author(s):  
Ourania E. Tsitsilonis ◽  
Dimitrios Paraskevis ◽  
Evi Lianidou ◽  
Evangelos Terpos ◽  
Athanasios Akalestos ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Clinical Symptoms ◽  
Binding Domain ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Humoral Immune ◽  
Protein Receptor ◽  
Previous Infection ◽  
And Gender ◽  
Asymptomatic Individuals

Between June and November 2020, we assessed plasma antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein in 4996 participants (aged 18–82 years, 34.5% men) from the National and Kapodistrian University of Athens. The weighted overall prevalence was 1.6% and monthly prevalence correlated with viral RNA-confirmed SARS-CoV-2 infections in Greece, in the same period. Notably, 49% of seropositive cases reported no history of SARS-CoV-2 infection-related clinical symptoms and 33% were unsuspected of their previous infection. Additionally, levels of anti-SARS-CoV-2 antibodies against the spike-protein receptor-binding domain were similar between symptomatic and asymptomatic individuals, irrespective of age and gender. Using Food and Drug Administration Emergency Use Authorization-approved assays, these results support the need for such studies on pandemic evaluation and highlight the development of robust humoral immune responses even among asymptomatic individuals. The high percentage of unsuspected/asymptomatic active cases, which may contribute to community transmission for more days than that of cases who are aware and self-isolate, underscores the necessity of measures across the population for the efficient control of the pandemic.

scholarly journals A 219-mer CHO-Expressing Receptor-Binding Domain of SARS-CoV S Protein Induces Potent Immune Responses and Protective Immunity

2010 ◽  
Vol 23 (2) ◽  
pp. 211-219 ◽  
Author(s):  
Lanying Du ◽  
Guangyu Zhao ◽  
Chris CS Chan ◽  
Lin Li ◽  
Yuxian He ◽  
...  
Keyword(s):  
Immune Responses ◽  
Receptor Binding ◽  
Protective Immunity ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
S Protein

scholarly journals A lymph node–targeted Amphiphile vaccine induces potent cellular and humoral immunity to SARS-CoV-2

2021 ◽  
Vol 7 (6) ◽  
pp. eabe5819
Author(s):  
Martin P. Steinbuck ◽  
Lochana M. Seenappa ◽  
Aniela Jakubowski ◽  
Lisa K. McNeil ◽  
Christopher M. Haqq ◽  
...  
Keyword(s):  
Immune Responses ◽  
Receptor Binding ◽  
Lung Parenchyma ◽  
Antibody Responses ◽  
Protein Subunit ◽  
T Helper 1 ◽  
Humoral Immune ◽  
Adaptive Immune ◽  
Humoral Immune Responses ◽  
Cellular And Humoral Immunity

The profound consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mandate urgent development of effective vaccines. Here, we evaluated an Amphiphile (AMP) vaccine adjuvant, AMP-CpG, composed of diacyl lipid–modified CpG, admixed with the SARS-CoV-2 Spike-2 receptor binding domain protein as a candidate vaccine (ELI-005) in mice. AMP modification efficiently delivers CpG to lymph nodes, where innate and adaptive immune responses are generated. Compared to alum, immunization with AMP-CpG induced >25-fold higher antigen-specific T cells that produced multiple T helper 1 (TH1) cytokines and trafficked into lung parenchyma. Antibody responses favored TH1 isotypes (IgG2c and IgG3) and potently neutralized Spike-2-ACE2 receptor binding, with titers 265-fold higher than natural convalescent patient COVID-19 responses; T cell and antibody responses were maintained despite 10-fold dose reduction in Spike antigen. Both cellular and humoral immune responses were preserved in aged mice. These advantages merit clinical translation to SARS-CoV-2 and other protein subunit vaccines.

scholarly journals 479 A lymph-node targeted amphiphile vaccine induces potent cellular and humoral immunity to SARS-CoV-2

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A513-A513
Author(s):  
Martin Steinbuck ◽  
Peter DeMuth ◽  
Lochana Seenappa ◽  
Christopher Haqq ◽  
Aniela Jakubowski ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Receptor Binding ◽  
Intracellular Cytokine Staining ◽  
T Cell Responses ◽  
Humoral Immune ◽  
Cell Responses ◽  
Humoral Immune Responses

BackgroundThe SARS-CoV-2 pandemic’s public health, economic, and social impacts mandate urgent development of effective vaccines to contain or eradicate infection. To that end, we evaluated a novel amphiphile (AMP) vaccine adjuvant, AMP-CpG, composed of diacyl lipid-modified CpG, admixed with the SARS-CoV-2 Spike-2 receptor binding domain (Spike RBD) protein for immunization (ELI 005) in two mouse models. AMP immunogens are efficiently delivered to lymph nodes, where innate and adaptive immune responses are generated.MethodsFemale, 6 to 8-week-old C57BL/6J and BALB/c mice and 37-week-old C57BL/6J mice received two or more doses of benchmark (alum or CpG) or AMP-modified vaccines, comprised of Spike RBD protein and AMP-CpG adjuvant, subcutaneously injected into the tail base in two-week intervals. Antigen was dose spared to determine if AMP-CpG would maintain the immune response. Cellular immune responses were determined via ELISpot analysis of IFNγ production by splenocytes, intracellular cytokine staining of peripheral blood and lung-resident T-cells, and flowcytometric bead array analysis of Th1/2/17 cytokines. Humoral immune responses were determined via blood serum ELISAs to determine sera antibody binding titers, and pseudoviral neutralization assays for comparison to human convalescent serum.ResultsCompared to alum, AMP immunization induced 29-fold higher antigen-specific T cells which produced multiple Th1 cytokines and trafficked into lung parenchyma. Antibody responses favored Th1 isotypes (IgG2bc, IgG3) and potently neutralized Spike-2-ACE2 receptor binding, with titers >100-fold higher than the natural immune response from convalescent COVID-19 patients; responses were maintained despite 10-fold dose-reduction in Spike antigen. Both cellular and humoral immune responses were preserved in aged mice.ConclusionsELI-005 exhibits the qualities of an optimal SARS-CoV-2 vaccine, which should (1) induce robust and durable CD8+ and CD4+ T cell responses, (2) elicit high magnitude neutralizing antibodies, (3) produce Th1 bias in the elicited antibody and T cell responses, (4) potentially expand pre-existing cross-reactive T cells, (5) enable dose-sparing of required immunogens to improve the speed and cost of broad vaccination campaigns, and (6) be efficacious in elderly populations. These advantages merit clinical translation to SARS-CoV-2 and other protein subunit vaccines.

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