Prediction of Conserved HLA Class I and Class II Epitopes from SARS-CoV-2 Licensed Vaccines Supports T-Cell Cross-Protection against SARS-CoV-1

Abstract

Heterologous immunity-inducing vaccines against different pathogens are necessary to deal with new pandemics. In this study, the possible impact of COVID-19 licensed formulations in the cytotoxic and the helper cellular immune responses against SARS-CoV-1 is analyzed for the 567 and 41 most abundant HLA class I and II alleles, respectively. Computational prediction showed that most of these 608 alleles, which cover >90% of the human population, contain enough conserved T-cell epitopes among SARS-CoV-1 and SARS-CoV-2 spike proteins. In addition, the vast majority of these predicted peptides were defined as epitopes recognized by CD4+ or CD8+ T lymphocytes, showing a very high correlation between the bioinformatics prediction and the experimental assays. These data suggest that both cytotoxic and helper cellular immune protection elicited by the currently licensed COVID-19 vaccines should be effective against SARS-CoV-1 infection. Lastly, this study has potential implications for public health against current and future pandemics, given that the SARS-CoV-1 vaccines in pipeline since the early 20th century could generate similarly cross-protection against COVID-19.

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“…Five noteworthy variants of SARS-CoV-2 were declared by WHO as Alpha, Beta, Gamma, Delta, and Omicron (Vass et al 2022 ). SARS-CoV-2 is a virus associated with the SARS-CoV-1 virus that triggered the 2002–2004 SARS outburst (Lopez 1622 ). COVID-19 was declared a pandemic in March/2020.…”

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“…Common HLA allotypes can be selected using computational techniques and bioinformatics resources, such as the SYFPEITHI and NetMHCpan ( 60 – 63 ) algorithms, and mutation-prone regions should be removed. Many functional SARS-CoV-2-derived T-cell epitopes have been identified and require further experimental validation ( 64 – 66 ). For effective B-cell epitope selection, the three-dimensional structure of the epitope is crucial.…”

Immunoinformatics lessons on the current COVID-19 pandemic and future coronavirus zoonoses

“…Thus, we used in silico approaches to overcome this challenge of herd immunity by analyzing the 600 most common HLA alleles covering > 90% of the world’s population regardless of ethnicity. We found that each of these most frequent HLA alleles could be able to present around 4-5 epitopes shared by SARS-CoV-1 and SARS-CoV-2 ( 8 ). Supporting our results, the scarce available data from slightly more than 200 SARS-CoV patients (limited to most prevalent and frequent HLA alleles) were highly concordant (91%) with our predicted epitopes ( 8 ).…”

“…We found that each of these most frequent HLA alleles could be able to present around 4-5 epitopes shared by SARS-CoV-1 and SARS-CoV-2 ( 8 ). Supporting our results, the scarce available data from slightly more than 200 SARS-CoV patients (limited to most prevalent and frequent HLA alleles) were highly concordant (91%) with our predicted epitopes ( 8 ). Because HLA genes are tightly linked in the genome, each individual expresses 6 to 12 different alleles (6 per chromosome) in a Mendelian fashion.…”

“…Because HLA genes are tightly linked in the genome, each individual expresses 6 to 12 different alleles (6 per chromosome) in a Mendelian fashion. Thus, a fully heterozygous person, as 85% of the world’s population is, could present up to 52 conserved viral epitopes ( 8 ), sufficient number to generate a complete cellular immune response. To support our argument, a recent study in mice demonstrated that immunization with SARS-CoV-1 vaccines induces, not only cytotoxic and helper T lymphocytes against SARS-CoV-2 as we hypothesized, but also some cross-reactive antibodies ( 9 ).…”