tetano
Editor, Senior Moderator
Front Genet
. 2021 Jun 23;12:684152.
doi: 10.3389/fgene.2021.684152. eCollection 2021.
A Peptide Vaccine Candidate Tailored to Individuals' Genetics Mimics the Multi-Targeted T Cell Immunity of COVID-19 Convalescent Subjects
Eszter Somogyi[SUP] 1 2 [/SUP], Zsolt Csiszovszki[SUP] 1 2 [/SUP], Levente Molnár[SUP] 1 2 [/SUP], Orsolya Lőrincz[SUP] 1 2 [/SUP], József Tóth[SUP] 1 2 [/SUP], Sofie Pattijn[SUP] 3 [/SUP], Jana Schockaert[SUP] 3 [/SUP], Aurélie Mazy[SUP] 3 [/SUP], István Miklós[SUP] 1 2 4 [/SUP], Katalin Pántya[SUP] 1 2 [/SUP], Péter Páles[SUP] 1 2 [/SUP], Enikő R Tőke[SUP] 1 2 [/SUP]
Affiliations
Abstract
Long-term immunity to coronaviruses likely stems from T cell activity. We present here a novel approach for the selection of immunoprevalent SARS-CoV-2-derived T cell epitopes using an in silico cohort of HLA-genotyped individuals with different ethnicities. Nine 30-mer peptides derived from the four major structural proteins of SARS-CoV-2 were selected and included in a peptide vaccine candidate to recapitulate the broad virus-specific T cell responses observed in natural infection. PolyPEPI-SCoV-2-specific, polyfunctional CD8[SUP]+[/SUP] and CD4[SUP]+[/SUP] T cells were detected in each of the 17 asymptomatic/mild COVID-19 convalescents' blood against on average seven different vaccine peptides. Furthermore, convalescents' complete HLA-genotype predicted their T cell responses to SARS-CoV-2-derived peptides with 84% accuracy. Computational extrapolation of this relationship to a cohort of 16,000 HLA-genotyped individuals with 16 different ethnicities suggest that PolyPEPI-SCoV-2 vaccination will likely elicit multi-antigenic T cell responses in 98% of individuals, independent of ethnicity. PolyPEPI-SCoV-2 administered with Montanide ISA 51 VG generated robust, Th1-biased CD8[SUP]+[/SUP], and CD4[SUP]+[/SUP] T cell responses against all represented proteins, as well as binding antibodies upon subcutaneous injection into BALB/c and hCD34[SUP]+[/SUP] transgenic mice modeling human immune system. These results have implications for the development of global, highly immunogenic, T cell-focused vaccines against various pathogens and diseases.
Keywords: HLA-genotype; SARS-CoV-2 immunity; ethnic diversity; global vaccine; in silico clinical trial.
. 2021 Jun 23;12:684152.
doi: 10.3389/fgene.2021.684152. eCollection 2021.
A Peptide Vaccine Candidate Tailored to Individuals' Genetics Mimics the Multi-Targeted T Cell Immunity of COVID-19 Convalescent Subjects
Eszter Somogyi[SUP] 1 2 [/SUP], Zsolt Csiszovszki[SUP] 1 2 [/SUP], Levente Molnár[SUP] 1 2 [/SUP], Orsolya Lőrincz[SUP] 1 2 [/SUP], József Tóth[SUP] 1 2 [/SUP], Sofie Pattijn[SUP] 3 [/SUP], Jana Schockaert[SUP] 3 [/SUP], Aurélie Mazy[SUP] 3 [/SUP], István Miklós[SUP] 1 2 4 [/SUP], Katalin Pántya[SUP] 1 2 [/SUP], Péter Páles[SUP] 1 2 [/SUP], Enikő R Tőke[SUP] 1 2 [/SUP]
Affiliations
- PMID: 34249101
- PMCID: PMC8261158
- DOI: 10.3389/fgene.2021.684152
Abstract
Long-term immunity to coronaviruses likely stems from T cell activity. We present here a novel approach for the selection of immunoprevalent SARS-CoV-2-derived T cell epitopes using an in silico cohort of HLA-genotyped individuals with different ethnicities. Nine 30-mer peptides derived from the four major structural proteins of SARS-CoV-2 were selected and included in a peptide vaccine candidate to recapitulate the broad virus-specific T cell responses observed in natural infection. PolyPEPI-SCoV-2-specific, polyfunctional CD8[SUP]+[/SUP] and CD4[SUP]+[/SUP] T cells were detected in each of the 17 asymptomatic/mild COVID-19 convalescents' blood against on average seven different vaccine peptides. Furthermore, convalescents' complete HLA-genotype predicted their T cell responses to SARS-CoV-2-derived peptides with 84% accuracy. Computational extrapolation of this relationship to a cohort of 16,000 HLA-genotyped individuals with 16 different ethnicities suggest that PolyPEPI-SCoV-2 vaccination will likely elicit multi-antigenic T cell responses in 98% of individuals, independent of ethnicity. PolyPEPI-SCoV-2 administered with Montanide ISA 51 VG generated robust, Th1-biased CD8[SUP]+[/SUP], and CD4[SUP]+[/SUP] T cell responses against all represented proteins, as well as binding antibodies upon subcutaneous injection into BALB/c and hCD34[SUP]+[/SUP] transgenic mice modeling human immune system. These results have implications for the development of global, highly immunogenic, T cell-focused vaccines against various pathogens and diseases.
Keywords: HLA-genotype; SARS-CoV-2 immunity; ethnic diversity; global vaccine; in silico clinical trial.