Identification of Novel Candidate Epitopes on SARS-CoV-2 Proteins for South America: A Review of HLA Frequencies by Country

Requena, David; Médico, Aldhair; Chacón, Ruy D.; Ramírez, Manuel; Marín-Sánchez, Obert

doi:10.3389/fimmu.2020.02008

Cited by 27 publications

(26 citation statements)

References 145 publications

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“…HLA-B*35 frequency in the Sri Lankan population is 21-23% [18,19]. In contrast, the most frequent HLA-A alleles in the European, US and Brazilian populations are HLA-A*0201, A*0206 (24.5 to 27.5%), which are several fold higher than in the Sri Lankan population, while HLA-A*2402 and B*3501 are lower (7.9 to 9.5%) [20][21][22]. In silico analysis, recently showed that HLA-A*0201 was associated with a higher risk of COVID-19, while HLA-A*2402 was shown to associate with higher capacity to present SARS-CoV2 antigens [23].…”

Section: Discussionmentioning

confidence: 84%

Identification of novel candidate CD8+ T cell epitopes of the SARS-CoV2 with homology to other seasonal coronaviruses

Pushpakumara

Madusanka

Danasekara

et al. 2021

Preprint

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Background Individuals who have not been exposed to the SARS-CoV2 virus have been shown to have T cells that respond to the virus, possibly due to the presence of cross-reactive T cell responses to other seasonal human coronaviruses (HCoVs). Such cross-reactive T cell immunity may lead to immunopathology or protection. Results To understand the influence of such cross-reactive T cell responses, we used IEDB (Immune epitope database) and NetMHCpan (ver. 4.1) to identify candidate CD8 + T cell epitopes, restricted through HLA-A and B alleles, which are seen in a frequency of > 10% in the Sri Lankan population. Conservation analysis was carried out for these candidate epitopes with the HCoVs, OC43, HKU1, NL63 and with the current circulating different variants of SARS-CoV2. 12/18 the candidate CD8 + T cell epitopes (binding score of ≥ 0.90), which had a high degree of homology (> 75%) with the other three HCoVs were within the NSP12 and NSP13 proteins. They were predicted to be restricted through HLA-A*2402, HLA-A*201, HLA-A*206 and HLA-B alleles B*3501. 31 candidate CD8 + T cell epitopes that were specific to SARS-CoV2 virus (< 25% homology with other HCoVs) were predominantly identified within the structural proteins (spike, envelop, membrane and nucleocapsid) and the NSP1, NSP2 and NSP3. They were predominantly restricted through HLA-B*3501 (6/31), HLA-B*4001 (6/31), HLA-B*4403(7/31) and HLA-A*2402 (8/31). The candidate CD8 + T cell epitopes that were homologous or were specific, with a binding score of ≥ 0.90, were found to be highly conserved within the SARS-CoV2 variants identified so far. Conclusions It would be crucial to understand T cell responses that associate with protection and the differences in the functionality and phenotype of epitope specific T cell responses, presented through different HLA alleles common in different geographical groups in order to understand disease pathogenesis.

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Section: Discussionmentioning

confidence: 84%

Identification of novel candidate CD8+ T cell epitopes of the SARS-CoV2 with homology to other seasonal coronaviruses

Pushpakumara

Madusanka

Danasekara

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…HLA-B*35 frequency in the Sri Lankan population is 21% to 23% [ 17 , 22 ]. In contrast, the most frequent HLA-A alleles in the European, US and Brazilian populations are HLA-A*0201 and A*0206 (24.5% to 27.5%), which are several fold higher than in the Sri Lankan population, while HLA-A*2402 and B*3501 are lower (7.9% to 9.5%) [ 23 , 24 , 25 ]. In silico analysis recently showed that HLA-A*0201 was associated with a higher risk of COVID-19, while HLA-A*2402 was shown to associate with higher capacity to present SARS-CoV2 antigens [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Candidate CD8+ T Cell Epitopes of the SARS-CoV2 with Homology to Other Seasonal Coronaviruses

Pushpakumara

Madhusanka

Dhanasekara

et al. 2021

Viruses

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Cross-reactive T cell immunity to seasonal coronaviruses (HCoVs) may lead to immunopathology or protection during SARS-CoV2 infection. To understand the influence of cross-reactive T cell responses, we used IEDB (Immune epitope database) and NetMHCpan (ver. 4.1) to identify candidate CD8+ T cell epitopes, restricted through HLA-A and B alleles. Conservation analysis was carried out for these epitopes with HCoVs, OC43, HKU1, and NL63. 12/18 the candidate CD8+ T cell epitopes (binding score of ≥0.90), which had a high degree of homology (>75%) with the other three HCoVs were within the NSP12 and NSP13 proteins. They were predicted to be restricted through HLA-A*2402, HLA-A*201, HLA-A*206, and HLA-B alleles B*3501. Thirty-one candidate CD8+ T cell epitopes that were specific to SARS-CoV2 virus (<25% homology with other HCoVs) were predominantly identified within the structural proteins (spike, envelop, membrane, and nucleocapsid) and the NSP1, NSP2, and NSP3. They were predominantly restricted through HLA-B*3501 (6/31), HLA-B*4001 (6/31), HLA-B*4403 (7/31), and HLA-A*2402 (8/31). It would be crucial to understand T cell responses that associate with protection, and the differences in the functionality and phenotype of epitope specific T cell responses, presented through different HLA alleles common in different geographical groups, to understand disease pathogenesis.

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“…A number of publications have investigated the link between HLA variation and COVID severity using this in silico approach. Some of these studies were combined with epidemiological data (29)(30)(31) or results derived from small case control series. (32) There appears to be no clear consensus in the conclusions drawn so far.…”

Section: Discussionmentioning

confidence: 99%

The Influence of Hla Genotype on Susceptibility To, and Severity Of, Covid-19 Infection

Langton¹,

Bourke

Lie

et al. 2021

Preprint

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BackgroundThe impact of COVID-19 varies markedly, not only between individual patients but also between different populations. We hypothesised that differences in human leukocyte antigen (HLA) genes might influence this variation.MethodsUsing next generation sequencing, we analysed the class I and class II classical HLA genes of 147 white British patients with variable clinical outcomes. 49 of these patients were admitted to hospital with severe COVID infection. They had no significant pre-existing comorbidities. We compared the results to those obtained from a group of 69 asymptomatic hospital workers who evidence of COVID exposure based on blood antibody testing. Allelic frequencies in both the severe and asymptomatic groups were compared to local and national healthy controls with adjustments made for age and sex. With the inclusion of hospital staff who had reported localised symptoms only (limited to loss of smell/taste, n=13) or systemic symptoms not requiring hospital treatment (n=16), we carried out ordinal logistic regression modelling to determine the relative influence of age, BMI, sex and the presence of specific HLA genes on symptomatology.FindingsWe found a significant difference in the allelic frequency of HLA-DRB1*04:01 in the severe patient compared to the asymptomatic staff group (5.1% versus 16.7%, p=0.003 after adjustment for age and sex). There was a significantly lower frequency of the haplotype DQA1*01:01/DQB1*05:01/DRB1*01:01 in the asymptomatic group compared to the background population (p=0.007). Ordinal logistic regression modelling confirmed the significant influence of DRB1*04:01 on the clinical severity of COVID-19 observed in the cohorts.InterpretationThis study provides evidence that patient age, sex, BMI and HLA genotype interact to determine the clinical outcome of COVID-19 infection.Research in contextEvidence before this studyHLA genes are implicated in host resistance or susceptibility to a range of pathogens. No studies thus far have compared HLA allele frequencies in patients requiring hospital admission following COVID-19 exposure to a group of asymptomatic individuals.Added value of this studyThe results indicate that the presence of HLA-DRB1*04:01 might confer protection from the development of respiratory failure following exposure to COVID. Individuals remaining asymptomatic following exposure to COVID are less likely to carry the haplotype DQA1*01:01/DQB1*05:01/DRB1*01:01 compared to the background population. This may indicate a host defence pathway not primarily dependent on an IgG response for clearance of infection. These findings conflict with larger genome wide association studies which compared HLA allelic frequencies of severely unwell patients with the background population.Implications of all the available evidenceThe findings could have implications for targeted vaccination regimes as well as helping assess the impact of social restrictions on mortality rates in different populations.

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Identification of Novel Candidate Epitopes on SARS-CoV-2 Proteins for South America: A Review of HLA Frequencies by Country

Abstract: tests. Additionally, the updated HLA allelic frequencies provide a better representation of South America and may impact different immunogenetic studies.

Cited by 27 publications

References 145 publications

Identification of novel candidate CD8+ T cell epitopes of the SARS-CoV2 with homology to other seasonal coronaviruses

Identification of novel candidate CD8+ T cell epitopes of the SARS-CoV2 with homology to other seasonal coronaviruses

Identification of Novel Candidate CD8+ T Cell Epitopes of the SARS-CoV2 with Homology to Other Seasonal Coronaviruses

The Influence of Hla Genotype on Susceptibility To, and Severity Of, Covid-19 Infection

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