Epitope-based Multi-variant SARS-Cov-2 Vaccine Design: Shared Epitopes Among the Natural SARS-Cov-2 Spike Glycoprotein and 5 of its Variants (D614G, α, β, γ, δ) with High in Silico Binding Affinity to Human Leukocyte Antigen (HLA) Class II Molecules

SARS-CoV-2 causes COVID-19, urgently requiring the development of effective vaccine(s). Much of current efforts focus on the SARS-CoV-2 spike-glycoprotein by identifying highly antigenic epitopes as good vaccine candidates. However, high antigenicity is not sufficient, since the activation of relevant T cells depends on the presence of the complex of the antigen with a suitably matching Human Leukocyte Antigen (HLA) Class II molecule, not the antigen alone: in the absence of such a match, even a highly antigenic epitope in vitro will not elicit antibody formation in vivo. Here we assessed systematically in silico the binding affinity of epitopes of the spike-glycoprotein to 66 common HLA-Class-II alleles (frequency ≥ 0.01). We used a sliding epitope window of 22-amino-acid-width to scan the entire protein and determined the binding affinity of each subsequence to each HLA allele. DPB1 had highest binding affinities, followed by DRB1 and DQB1. Higher binding affinities were concentrated in the initial part of the glycoprotein (S1-S460), with a peak at S223-S238. This region would be well suited for effective vaccine development by ensuring high probability for successful matching of the vaccine antigen from that region to a HLA Class II molecule for CD4+ T cell activation by the antigen-HLA molecule complex.

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In silico investigation of binding affinities between human leukocyte antigen class I molecules and SARS-CoV-2 virus spike and ORF1ab proteins

10.37349/ei.2021.00003 ◽

2021 ◽

Author(s):

Spyros A. Charonis ◽

Effie-Photini Tsilibary ◽

Apostolos P. Georgopoulos

Keyword(s):

Human Leukocyte Antigen ◽

In Silico ◽

Human Leukocyte ◽

Hla Class I ◽

Hla Class Ii ◽

Class I ◽

Binding Affinities ◽

S Protein ◽

Leukocyte Antigen ◽

Hla Class I Molecules

Aim: The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019, a global pandemic. There is hence an urgent need for effective approaches to understand the mechanism of viral interaction with immune cells that lead to viral elimination and subsequent long-term immunity. The first, immediate response to the viral infection involves mobilization of native immunity and human leukocyte antigen (HLA) class I mechanisms to kill infected cells and eliminate the virus. The second line of defense involves the activation of HLA class II system for the production of antibodies against the virus which will add to the elimination of the virus and prevent future infections. In a previous study, investigated the relations between SARS-CoV-2 spike glycoprotein (S protein) and HLA class II alleles were investigaed; here report on the relations of the S protein and the open reading frame 1ab (ORF1ab) of SARS-CoV-2 to HLA class I alleles. Methods: An in silico sliding window approach was used to determine exhaustively the binding affinities of linear epitopes of 10 amino acid length (10-mers) to each of 61 common (global frequency ≥ 0.01) HLA class I molecules (17, 24 and 20 from gene loci A, B and C, respectively). A total of 8,354 epitopes were analyzed; 1,263 from the S protein and 7,091 from ORF1ab. Results: HLA-A genes were the most effective at binding SARS-CoV-2 epitopes for both spike and ORF1ab proteins. Good binding affinities were found for all three genes and were distributed throughout the length of the S protein and ORF1ab polyprotein sequence. Conclusions: Common HLA class I molecules, as a population, are very well suited to binding with high affinity to SARS-CoV-2 spike and ORF1ab proteins and hence should be effective in aiding the early elimination of the virus.

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Binding of Human Thyrotropin Receptor Peptides to a Graves’ Disease-Predisposing Human Leukocyte Antigen Class II Molecule

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.85.3.6376 ◽

2000 ◽

Vol 85 (3) ◽

pp. 1176-1179 ◽

Cited By ~ 1

Author(s):

Yoshikuni Sawai ◽

Leslie J. DeGroot

Keyword(s):

Human Leukocyte Antigen ◽

Human Leukocyte ◽

Class Ii ◽

Hla Class Ii ◽

Graves Disease ◽

T Cell Repertoire ◽

Thyrotropin Receptor ◽

Cell Repertoire ◽

Peptide Epitopes ◽

Leukocyte Antigen

Abstract Abstract There are many reports that Graves’ disease (GD) is associated with certain human leukocyte antigen (HLA) molecules, in particular DR3. Here we examined the characteristics of binding of human TSH receptor (TSHR) peptides to this disease-associated HLA class II molecule. DR3 molecules bind TSHR immuonodominant peptide epitopes with intermediate affinity. On the contrary, DR3 binds nonimmunogenic peptides either with poor affinity or not at all, with one exceptional peptide that has extremely high affinity. These results suggest that susceptibility to GD associated with inheritance of a specific HLA class II gene is due to the influence of the HLA molecule-TSHR peptide complex on the T cell repertoire.

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The Human Leukocyte Antigen Class II Immunopeptidome of the SARS-CoV-2 Spike Glycoprotein

Cell Reports ◽

10.1016/j.celrep.2020.108454 ◽

2020 ◽

Vol 33 (9) ◽

pp. 108454

Author(s):

Michael D. Knierman ◽

Megan B. Lannan ◽

Laura J. Spindler ◽

Carl L. McMillian ◽

Robert J. Konrad ◽

...

Keyword(s):

Human Leukocyte Antigen ◽

Human Leukocyte Antigen Class ◽

Human Leukocyte ◽

Class Ii ◽

Spike Glycoprotein ◽

Leukocyte Antigen

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Human Leukocyte Antigen (HLA) Class II Expression on Regulatory T Cells (Tregs) Isolated from Discarded Human Thymus is Induced by In Vitro Expansion Conditions

The Journal of Heart and Lung Transplantation ◽

10.1016/j.healun.2020.01.755 ◽

2020 ◽

Vol 39 (4) ◽

pp. S178-S179

Author(s):

E. Dijke ◽

T. Ellis ◽

I. Larsen ◽

I. Rebeyka ◽

D. Freed ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Human Leukocyte Antigen ◽

Human Leukocyte ◽

Class Ii ◽

Hla Class Ii ◽

Leukocyte Antigen ◽

Human Thymus ◽

In Vitro Expansion

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Susceptible and Protective Human Leukocyte Antigen Class II Alleles and Haplotypes in Bahraini Type 2 (Non-Insulin-Dependent) Diabetes Mellitus Patients

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.12.1.213-217.2005 ◽

2005 ◽

Vol 12 (1) ◽

pp. 213-217 ◽

Cited By ~ 8

Author(s):

Ayesha A. Motala ◽

Marc Busson ◽

Einas M. Al-Harbi ◽

Manal A. A. Khuzam ◽

Emtiaz M. D. Al-Omari ◽

...

Keyword(s):

Type 2 Diabetes ◽

Type 1 Diabetes ◽

Human Leukocyte Antigen ◽

Human Leukocyte ◽

Class Ii ◽

Hla Class Ii ◽

Leukocyte Antigen ◽

Insulin Dependent

ABSTRACT Whereas the genetic risk for type 1 diabetes is linked to human leukocyte antigen (HLA) class II genes, the HLA association in type 2 (non-insulin-dependent) diabetes is less clear. The association between HLA class II genotypes and type 2 diabetes was examined in adult Bahrainis, an Arab population with a high prevalence of type 2 diabetes. HLA-DRB1* and -DQB1* genotyping of 86 unrelated type 2 diabetes patients (age, 51.6 ± 8.2 years; mean duration of diabetes, 7.7 ± 7.1 years) who had a strong family history of diabetes (52 of 72 versus 0 of 89 for controls, P < 0.001) and 89 healthy subjects was done by PCR-sequence-specific priming. DRB1*040101 (0.1221 versus 0.0562, P = 0.019) and DRB1*070101 (0.2151 versus 0.0843, P < 0.001) were positively associated, while DRB1*110101 (0.0698 versus 0.1461, P = 0.014) and DRB1*160101 (0.0640 versus 0.1236, P = 0.038) were negatively associated with type 2 diabetes. DRB1*040101-DQB1*0302 (0.069 versus 0.0007; P = 0.004), DRB1*070101-DQB1*0201 (0.178 versus 0.0761, P = 0.007), DRB1*070101-DQB1*050101 (0.125 versus 0.0310, P = 0.002), and DRB1*150101-DQB1*060101 (0.0756 versus 0.0281, P = 0.008) were more prevalent among patients, while DRB1*160101-DQB1*050101 (0.0702 versus 0.0349, P = 0.05) was more prevalent among controls, conferring disease susceptibility or protection, respectively. In Bahrainis with type 2 diabetes, there is a significant association with select HLA class II genotypes, which were distinct from those in type 1 diabetes.

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Human Leukocyte Antigen-DR Expression is Significantly Related to an Increased Disease-Free and Disease-Specific Survival in Patients With Cervical Adenocarcinoma

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000783 ◽

2016 ◽

Vol 26 (8) ◽

pp. 1503-1509 ◽

Cited By ~ 6

Author(s):

Sanne Samuels ◽

Vivian M. Spaans ◽

Michelle Osse ◽

Lex A.W. Peters ◽

Gemma G. Kenter ◽

...

Keyword(s):

Human Leukocyte Antigen ◽

Squamous Cell ◽

Human Leukocyte ◽

Class Ii ◽

Hla Class Ii ◽

Disease Specific Survival ◽

Leukocyte Antigen ◽

Class Ii Antigens ◽

Disease Free ◽

Disease Specific

ObjectivesHuman leukocyte antigen (HLA) class II antigens are expressed on antigen-presenting cells, that is, macrophages, dendritic cells, and B lymphocytes. Under the influence of IFN-γ, HLA class II molecules can also be expressed on T lymphocytes, epithelial and endothelial cells. In addition, HLA class II antigens can be expressed in a variety of malignancies; however, the link with prognosis and ultimately patient survival is controversial.MethodsThe pattern of HLA-DRA expression in cervical carcinoma was studied using immunohistochemistry. In total, 124 cervical carcinomas were examined, of which 60 (48.4%) were squamous cell carcinomas and 64 (51.6%) were adenocarcinomas.ResultsIn squamous cell carcinoma, HLA-DRA was expressed in 41 (68.3%) of 60 tumors, whereas in adenocarcinoma, HLA-DRA was expressed in 60 (93.8%) of 64 tumors (P< 0.001). In adenocarcinoma, HLA-DRA expression was associated with an increased disease-free survival (211.0 ± 13.0 vs 53.3 ± 30.5 months;P= 0.004) and disease-specific survival (226.45 ± 11.5 vs 75.8 ± 27.6 months;P= 0.002).ConclusionsUpregulation of HLA-DRA is significantly related to an increased disease-free and disease-specific survival in cervical adenocarcinoma. These data warrant further analysis of the functional role of HLA-DRA in these tumors.

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