scholarly journals Medical Countermeasures Analysis of 2019-nCoV and Vaccine Risks for Antibody-Dependent Enhancement (ADE)

2020 ◽  
Author(s):  
Darrell O. Ricke ◽  
Robert W. Malone
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
Amino Acid Residue ◽  
Antiviral Drug ◽  
Cell Vaccine ◽  
Variation Analysis ◽  
S Protein ◽  
Antibody Dependent Enhancement ◽  
T Effector Cells ◽  
Reduce Risk

Background: In 80% of patients, COVID-19 presents as mild disease1,2. 20% of cases develop severe (13%) or critical (6%) illness. More severe forms of COVID-19 present as clinical severe acute respiratory syndrome, but include a T-predominant lymphopenia3, high circulating levels of proinflammatory cytokines and chemokines, accumulation of neutrophils and macrophages in lungs, and immune dysregulation including immunosuppression4. Methods: All major SARS-CoV-2 proteins were characterized using an amino acid residue variation analysis method. Results predict that most SARS-CoV-2 proteins are evolutionary constrained, with the exception of the spike (S) protein extended outer surface. Results were interpreted based on known SARS-like coronavirus virology and pathophysiology, with a focus on medical countermeasure development implications. Findings: Non-neutralizing antibodies to variable S domains may enable an alternative infection pathway via Fc receptor-mediated uptake. This may be a gating event for the immune response dysregulation observed in more severe COVID-19 disease. Prior studies involving vaccine candidates for FCoV5,6 SARS-CoV-17-10 and Middle East Respiratory Syndrome coronavirus (MERS-CoV) 11 demonstrate vaccination-induced antibody-dependent enhancement of disease (ADE), including infection of phagocytic antigen presenting cells (APC). T effector cells are believed to play an important role in controlling coronavirus infection; pan-T depletion is present in severe COVID-19 disease3 and may be accelerated by APC infection. Sequence and structural conservation of S motifs suggests that SARS and MERS vaccine ADE risks may foreshadow SARS-CoV-2 S-based vaccine risks. Autophagy inhibitors may reduce APC infection and T-cell depletion12 13. Amino acid residue variation analysis identifies multiple constrained domains suitable as T cell vaccine targets. Evolutionary constraints on proven antiviral drug targets present in SARS-CoV-1 and SARS-CoV-2 may reduce risk of developing antiviral drug escape mutants. Interpretation: Safety testing of COVID-19 S protein-based B cell vaccines in animal models is strongly encouraged prior to clinical trials to reduce risk of ADE upon virus exposure.

scholarly journals A natural mutation of the amino acid residue at position 60 destroys staphylococcal enterotoxin A murine T-cell mitogenicity.

1995 ◽  
Vol 63 (8) ◽  
pp. 2826-2832 ◽  
Author(s):  
W Mahana ◽  
R al-Daccak ◽  
C Lévéillé ◽  
J P Valet ◽  
J Hébert ◽  
...  
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
Amino Acid Residue ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin A ◽  
Natural Mutation

Critical role of an amino acid residue in a T cell determinant is due to its interaction with a neighboring non-critical residue

1990 ◽  
Vol 20 (9) ◽  
pp. 2145-2148 ◽  
Author(s):  
Michel Boyer ◽  
Zuzana Novak ◽  
Arun Fotedar ◽  
Ester Fraga ◽  
Bhagirath Singh
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
Amino Acid Residue ◽  
Critical Role ◽  
Critical Residue

scholarly journals A Bioinformatics Approach for the Prediction of Immunogenic Properties and Structure of the SARS-COV-2 B.1.617.1 Variant Spike Protein

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Vijay Kumar Srivastava ◽  
Sanket Kaushik ◽  
Gazal Bhargava ◽  
Ajay Jain ◽  
Juhi Saxena ◽  
...  
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
B Cell ◽  
In Silico ◽  
Tertiary Structure ◽  
In Silico Analysis ◽  
Respiratory Illness ◽  
T Cell Epitopes ◽  
S Protein ◽  
Immunogenic Properties

Background. B.1.617.1, a variant of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causing respiratory illness is responsible for the second wave of COVID-19 and associated with a high incidence of infectivity and mortality. To mitigate the B.1.617.1 variant of SARS-CoV-2, deciphering the protein structure and immunological responses by employing bioinformatics tools for data mining and analysis is pivotal. Objectives. Here, an in silico approach was employed for deciphering the structure and immune function of the subunit of spike (S) protein of SARS-CoV-2 B.1.617.1 variant. Methods. The partial amino acid sequence of SARS-CoV-2 B.1.617.1 variant S protein was analyzed, and its putative secondary and tertiary structure was predicted. Immunogenic analyses including B- and T-cell epitopes, interferon-gamma (IFN-γ) response, chemokine, and protective antigens for SARS-CoV 2 S proteins were predicted using appropriate tools. Results. B.1.617.1 variant S protein sequence was found to be highly stable and amphipathic. ABCpred and CTLpred analyses led to the identification of two potential antigenic B cell and T cell epitopes with starting amino acid positions at 60 and 82 (for B cell epitopes) and 54 and 98 (for T cell epitopes) having prediction scores > 0.8 . Further, RAMPAGE tool was used for determining the allowed and disallowed regions of the three-dimensional predicted structure of SARS-CoV-2 B.1.617.1 variant S protein. Conclusion. Together, the in silico analysis revealed the predicted structure of partial S protein, immunogenic properties, and possible regions for S protein of SARS-CoV-2 and provides a valuable prelude for engineering the targeted vaccine or drug against B.1.617.1 variant of SARS-CoV-2.

scholarly journals The SARS-CoV-2 receptor-binding domain elicits a potent neutralizing response without antibody-dependent enhancement

2020 ◽  
Author(s):  
Brian D. Quinlan ◽  
Huihui Mou ◽  
Lizhou Zhang ◽  
Yan Guo ◽  
Wenhui He ◽  
...  
Keyword(s):  
Amino Acid ◽  
Receptor Binding ◽  
Neutralizing Antibody ◽  
Binding Domain ◽  
Entry Inhibitor ◽  
Receptor Binding Domain ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Antibody Dependent Enhancement ◽  
Acid Fragment

SUMMARYThe SARS-coronavirus 2 (SARS-CoV-2) spike (S) protein mediates entry of SARS-CoV-2 into cells expressing the angiotensin-converting enzyme 2 (ACE2). The S protein engages ACE2 through its receptor-binding domain (RBD), an independently folded 197-amino acid fragment of the 1273-amino acid S-protein protomer. Antibodies to the RBD domain of SARS-CoV (SARS-CoV-1), a closely related coronavirus which emerged in 2002-2003, have been shown to potently neutralize SARS-CoV-1 S-protein-mediated entry, and the presence of anti-RBD antibodies correlates with neutralization in SARS-CoV-2 convalescent sera. Here we show that immunization with the SARS-CoV-2 RBD elicits a robust neutralizing antibody response in rodents, comparable to 100 µg/ml of ACE2-Ig, a potent SARS-CoV-2 entry inhibitor. Importantly, anti-sera from immunized animals did not mediate antibody-dependent enhancement (ADE) of S-protein-mediated entry under conditions in which Zika virus ADE was readily observed. These data suggest that an RBD-based vaccine for SARS-CoV-2 could be safe and effective.

Sign in / Sign up

Export Citation Format

Share Document