scholarly journals SARS-CoV-2 variants: A double-edged sword?

2021 ◽  
pp. 153537022110141
Author(s):  
Manasi P Jogalekar ◽  
Anurag Veerabathini ◽  
Prakash Gangadaran
Keyword(s):  
Immune Response ◽  
Disease Severity ◽  
Vaccine Efficacy ◽  
Neutralizing Antibodies ◽  
Viral Evolution ◽  
Herd Immunity ◽  
Spike Protein ◽  
Local Strains ◽  
Risk Of Death ◽  
Main Target

Since the worldwide emergence of the COVID-19 outbreak, there have been international concerns about the possible viral evolution into variants with underlying mutations that may contribute to their increased transmissibility, disease severity, risk of death, and their potential escape from the immune response or may even lead to its extinction. Rigorous surveillance has revealed the variants harboring mutations in the spike protein, the main target of neutralizing antibodies generated through vaccination or herd immunity. In this review, we have highlighted major SARS-CoV-2 variants as well as other local strains along with their specific mutations, suspected changes in their characteristics, and their impact on the current pandemic and vaccine efficacy. We have also emphasized the need to develop widely protective interventions to curb further transmission of variants.

scholarly journals In Vivo Study of the HC-TN Strain of Hepatitis C Virus Recovered from a Patient with Fulminant Hepatitis: RNA Transcripts of a Molecular Clone (pHC-TN) Are Infectious in Chimpanzees but Not in Huh7.5 Cells

2007 ◽  
Vol 81 (13) ◽  
pp. 7208-7219 ◽  
Author(s):  
Akito Sakai ◽  
Shingo Takikawa ◽  
Robert Thimme ◽  
Jean-Christophe Meunier ◽  
Hans Christian Spangenberg ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Immune Responses ◽  
Disease Severity ◽  
Neutralizing Antibodies ◽  
Viral Evolution ◽  
Acute Infection ◽  
Hcv Infection ◽  
Rna Transcripts

ABSTRACT Both viral and host factors are thought to influence the pathogenesis of hepatitis C virus (HCV) infection. We studied strain HC-TN (genotype 1a), which caused fulminant hepatic failure in a patient and, subsequently, severe hepatitis in a chimpanzee (CH1422), to analyze the relationship between disease severity, host immune response, viral evolution, and outcome. A second chimpanzee (CH1581) was infected from CH1422 plasma, and a third chimpanzee (CH1579) was infected from RNA transcripts of a consensus cDNA of HC-TN (pHC-TN). RNA transcripts of pHC-TN did not replicate in Huh7.5 cells, which were recently found to be susceptible to infection with another fulminant HCV strain (JFH1). The courses of viremia were similar in the three animals. However, CH1581 and CH1579 developed a less severe acute hepatitis than CH1422. CH1579 and CH1422 resolved the infection, whereas CH1581 became persistently infected. CH1579 and CH1581, despite their differing outcomes, both developed significant intrahepatic cellular immune responses, but not antibodies to the envelope glycoproteins or neutralizing antibodies, during the acute infection. We analyzed the polyprotein sequences of virus recovered at five and nine time points from CH1579 and CH1581, respectively, during the first year of follow-up. High mutation rates and high proportions of nonsynonymous mutations suggested immune pressure and positive selection in both animals. Changes were not selected until after the initial decrease in virus titers and after the development of immune responses and hepatitis. Subsequently, however, mutations emerged repeatedly in both animals. Overall, our results indicate that disease severity and outcome of acute HCV infection depend primarily on the host response.

scholarly journals Prediction and evolution of the molecular fitness of SARS-CoV-2 variants: Introducing SpikePro

2021 ◽  
Author(s):  
Fabrizio Pucci ◽  
Marianne Rooman
Keyword(s):  
Immune Response ◽  
Neutralizing Antibodies ◽  
Molecular Mechanisms ◽  
Population Level ◽  
Critical Issue ◽  
Spike Protein ◽  
Human Immune Response ◽  
Human Immune ◽  
The Stability ◽  
The Impact

The understanding of the molecular mechanisms driving the fitness of the SARS-CoV-2 virus and its mutational evolution is still a critical issue. We built a simplified computational model, called SpikePro, to predict the SARS-CoV-2 fitness from the amino acid sequence and structure of the spike protein. It contains three contributions: the viral transmissibility predicted from the stability of the spike protein, the infectivity computed in terms of the affinity of the spike protein for the ACE2 receptor, and the ability of the virus to escape from the human immune response based on the binding affinity of the spike protein for a set of neutralizing antibodies. Our model reproduces well the available experimental, epidemiological and clinical data on the impact of variants on the biophysical characteristics of the virus. For example, it is able to identify circulating viral strains that, by increasing their fitness, recently became dominant at the population level. SpikePro is a useful instrument for the genomic surveillance of the SARS-CoV-2 virus, since it predicts in a fast and accurate way the emergence of new viral strains and their dangerousness. It is freely available in the GitHub repository github.com/3BioCompBio/SpikeProSARS-CoV-2.

scholarly journals Neutralizing Monoclonal Antibodies That Target the Spike Receptor Binding Domain Confer Fc Receptor-Independent Protection against SARS-CoV-2 Infection in Syrian Hamsters

mBio ◽  
2021 ◽  
Author(s):  
Wen Su ◽  
Sin Fun Sia ◽  
Aaron J. Schmitz ◽  
Traci L. Bricker ◽  
Tyler N. Starr ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Fc Receptor ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Syrian Hamsters ◽  
Convalescent Phase ◽  
Main Target

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein is the main target for neutralizing antibodies. These antibodies can be elicited through immunization or passively transferred as therapeutics in the form of convalescent-phase sera or monoclonal antibodies (MAbs).

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 Antibody response to SARS-CoV-2 infection and BNT162b2 vaccine in Israel

2021 ◽  
Author(s):  
Guy Shapira ◽  
Ramzia Abu Hamad ◽  
Chen Weiner ◽  
Nir Rainy ◽  
Reut Sorek-Abramovich ◽  
...  
Keyword(s):  
Immune Response ◽  
Viral Entry ◽  
Neutralizing Antibodies ◽  
Host Cells ◽  
Spike Protein ◽  
Igg Antibodies ◽  
Age And Gender ◽  
Specific Igg ◽  
And Gender ◽  
Specific Igg Antibodies

Neutralizing antibodies targeting the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) block viral entry to host cells, preventing disease and further spread of the pathogen. The presence of SARS-CoV-2 antibodies in serum is a reliable indicator of infection, used epidemiologically to estimate the prevalence of infection and clinically as a measurement of an antigen-specific immune response. In this study, we analyzed serum Spike protein-specific IgG antibodies from 26,170 samples, including convalescent individuals who had coronavirus disease 2019 (COVID-19) and recipients of the BNT162b2 vaccine. We find distinct serological patterns in COVID-19 convalescent and vaccinated individuals, correlated with age and gender and the presence symptoms.

scholarly journals The Kinetics of Humoral Response and its Relationship with the Disease Severity in COVID-19

2020 ◽  
Author(s):  
Lili Ren ◽  
Lulu Zhang ◽  
De Chang ◽  
Li Guo ◽  
Junwen Wang ◽  
...  
Keyword(s):  
Disease Severity ◽  
Neutralizing Antibodies ◽  
Late Onset ◽  
Humoral Response ◽  
Spike Protein ◽  
Appearance Time ◽  
Global Pandemic ◽  
Antibody Titers ◽  
Kinetics Of

Abstract Coronavirus Disease 2019 (COVID-19) has caused global pandemic. Here we profiled the humoral response against SARS-CoV-2 by measuring immunoglobulin (Ig) A, IgM and IgG against nucleocapsid, spike proteins and IgM, IgG antibodies against receptor-binding domain (RBD) of the spike protein along with total neutralizing antibodies. We tested 279 plasma samples collected from 176 COVID-19 patients. We demonstrate more severe cases have a late onset in the humoral response compared to mild/moderate infections. All the antibody titers continue to rise in patients with COVID-19 over the disease course. However, these levels are mostly unrelated to the disease severity. The appearance time and titers of neutralizing antibodies showed significant positive correlation to the antibodies against spike protein. Our results suggest late onset of antibody response as a risk factor for disease severity, however there is a limited role of antibody titers in predicting disease severity of COVID-19.

scholarly journals Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 Spike protein for neutralization assays

2020 ◽  
Author(s):  
Katharine H.D. Crawford ◽  
Rachel Eguia ◽  
Adam S. Dingens ◽  
Andrea N. Loes ◽  
Keara D. Malone ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Spike Protein ◽  
Single Cycle ◽  
Viral Particles ◽  
Main Target ◽  
Human Sera ◽  
Level 3 ◽  
Valuable Complement ◽  
Level 2 ◽  
Biosafety Level

AbstractSARS-CoV-2 enters cells using its Spike protein, which is also the main target of neutralizing antibodies. Therefore, assays to measure how antibodies and sera affect Spike-mediated viral infection are important for studying immunity. Because SARS-CoV-2 is a biosafety-level-3 virus, one way to simplify such assays is to pseudotype biosafety-level-2 viral particles with Spike. Such pseudotyping has now been described for single-cycle lentiviral, retroviral and VSV particles, but the reagents and protocols are not widely available. Here we detail how to effectively pseudotype lentiviral particles with SARS-CoV-2 Spike and infect 293T cells engineered to express the SARS-CoV-2 receptor, ACE2. We also make all the key experimental reagents available in the BEI Resources repository of ATCC and the NIH. Furthermore, we demonstrate how these pseudotyped lentiviral particles can be used to measure the neutralizing activity of human sera or plasma against SARS-CoV-2 in convenient luciferase-based assays, thereby providing a valuable complement to ELISA-based methods that measure antibody binding rather than neutralization.

scholarly journals Immune response to vaccine candidates based on different types of nanoscaffolded RBD domain of the SARS-CoV-2 spike protein

2020 ◽  
Author(s):  
Duško Lainšček ◽  
Tina Fink ◽  
Vida Forstnerič ◽  
Iva Hafner-Bratkovič ◽  
Sara Orehek ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cell ◽  
Neutralizing Antibodies ◽  
Affinity Maturation ◽  
T Cell Response ◽  
Spike Protein ◽  
Cytotoxic Lymphocytes ◽  
Protein Antigens ◽  
Vaccine Platform ◽  
Suitable Target

AbstractEffective and safe vaccines against SARS-CoV-2 are highly desirable to prevent casualties and societal cost caused by Covid-19 pandemic. The receptor binding domain (RBD) of the surface-exposed spike protein of SARS-CoV-2 represents a suitable target for the induction of neutralizing antibodies upon vaccination. Small protein antigens typically induce weak immune response while particles measuring tens of nanometers are efficiently presented to B cell follicles and subsequently to follicular germinal center B cells in draining lymph nodes, where B cell proliferation and affinity maturation occurs. Here we prepared and analyzed the response to several DNA vaccines based on genetic fusions of RBD to four different scaffolding domains, namely to the foldon peptide, ferritin, lumazine synthase and β-annulus peptide, presenting from 6 to 60 copies of the RBD on each particle. Scaffolding strongly augmented the immune response with production of neutralizing antibodies and T cell response including cytotoxic lymphocytes in mice upon immunization with DNA plasmids. The most potent response was observed for the 24-residue β-annulus peptide scaffold that forms large soluble assemblies, that has the advantage of low immunogenicity in comparison to larger scaffolds. Our results support the advancement of this vaccine platform towards clinical trials.

scholarly journals Linear epitopes of SARS-CoV-2 spike protein elicit neutralizing antibodies in COVID-19 patients

2020 ◽  
Author(s):  
Yang Li ◽  
Dan-yun Lai ◽  
Hai-nan Zhang ◽  
He-wei Jiang ◽  
Xiao-long Tian ◽  
...  
Keyword(s):  
Immune Response ◽  
Neutralizing Antibodies ◽  
World Wide ◽  
Cell Entry ◽  
Spike Protein ◽  
Peptide Microarray ◽  
S Protein ◽  
Linear Epitopes

AbstractSARS-CoV-2 outbreak is a world-wide pandemic. The Spike protein plays central role in cell entry of the virus, and triggers significant immuno-response. Our understanding of the immune-response against S protein is still very limited. Herein, we constructed a peptide microarray and analyzed 55 convalescent sera, three areas with rich linear epitopes were identified. Potent neutralizing antibodies enriched from sera by 3 peptides, which do not belong to RBD were revealed.

scholarly journals The kinetics of humoral response and its relationship with the disease severity in COVID-19

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Lili Ren ◽  
Lulu Zhang ◽  
De Chang ◽  
Junwen Wang ◽  
Yongfeng Hu ◽  
...  
Keyword(s):  
Disease Severity ◽  
Neutralizing Antibodies ◽  
Late Onset ◽  
Geometric Mean ◽  
Humoral Response ◽  
Spike Protein ◽  
Appearance Time ◽  
Global Pandemic ◽  
Antibody Titers

AbstractCoronavirus Disease 2019 (COVID-19) has caused a global pandemic. Here we profiled the humoral response against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by measuring immunoglobulin (Ig) A, IgM, and IgG against nucleocapsid and spike proteins, along with IgM and IgG antibodies against receptor-binding domain (RBD) of the spike protein and total neutralizing antibodies (NAbs). We tested 279 plasma samples collected from 176 COVID-19 patients who presented and enrolled at different stages of their disease. Plasma dilutions were optimized and based on the data, a single dilution of plasma was used. The mean absorbance at 450 nm was measured for Ig levels and NAbs were measured using geometric mean titers. We demonstrate that more severe cases have a late-onset in the humoral response compared to mild/moderate infections. All the antibody titers continue to rise in patients with COVID-19 over the disease course. However, these levels are mostly unrelated to disease severity. The appearance time and titers of NAbs showed a significant positive correlation to the antibodies against spike protein. Our results suggest the late onset of antibody response as a risk factor for disease severity, however, there is a limited role of antibody titers in predicting disease severity of COVID-19.

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