1887

Abstract

The pandemic caused by SARS-CoV-2 has led to the successful development of effective vaccines however the prospect of variants of SARS-CoV-2 and future coronavirus outbreaks necessitates the investigation of other vaccine strategies capable of broadening vaccine mediated T-cell responses and potentially providing cross-immunity. In this study the SARS-CoV-2 proteome was assessed for clusters of immunogenic epitopes restricted to diverse human leucocyte antigen. These regions were then assessed for their conservation amongst other coronaviruses representative of different alpha and beta coronavirus genera. Sixteen highly conserved peptides containing numerous HLA class I and II restricted epitopes were synthesized from these regions and assessed for their antigenicity against T-cells from individuals with previous SARS-CoV-2 infection. Monocyte derived dendritic cells were generated from these peripheral blood mononuclear cells (PBMC), loaded with SARS-CoV-2 peptides, and used to induce autologous CD4+ and CD8+ T cell activation. The SARS-CoV-2 peptides demonstrated antigenicity against the T-cells from individuals with previous SARS-CoV-2 infection indicating that this approach holds promise as a method to activate anti-SAR-CoV-2 T-cell responses from conserved regions of the virus which are not included in vaccines utilising the Spike protein.

Keyword(s): peptide , SARS-CoV-2 , T-cells and vaccine
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.001698
2022-01-11
2022-01-17
Loading full text...

Full text loading...

/deliver/fulltext/jgv/103/1/jgv001698.html?itemId=/content/journal/jgv/10.1099/jgv.0.001698&mimeType=html&fmt=ahah

References

  1. The Lancet Respiratory Medicine Realising the potential of SARS-CoV-2 vaccines-a long shot. Lancet Respir Med 2021; 9:117 [View Article]
    [Google Scholar]
  2. Arashkia A, Jalilvand S, Mohajel N et al. SARS CoV-2 Rapid Response Team of Pasteur Institute of Iran (PII). Severe acute respiratory syndrome-coronavirus-2 spike (S) protein based vaccine candidates: State of the art and future prospects. Rev Med Virol 2021; 31:e2183 [View Article]
    [Google Scholar]
  3. Williams TC, Burgers WA. SARS-CoV-2 evolution and vaccines: cause for concern?. Lancet Respir Med 2021; 9:333–335 [View Article] [PubMed]
    [Google Scholar]
  4. Wu L-P, Wang N-C, Chang Y-H, Tian X-Y, Na D-Y et al. Duration of antibody responses after severe acute respiratory syndrome. Emerg Infect Dis 2007; 13:1562–1564 [View Article] [PubMed]
    [Google Scholar]
  5. Ng O-W, Chia A, Tan AT, Jadi RS, Leong HN et al. Memory T cell responses targeting the SARS coronavirus persist up to 11 years post-infection. Vaccine 2016; 34:2008–2014 [View Article] [PubMed]
    [Google Scholar]
  6. Nelde A, Bilich T, Heitmann JS, Maringer Y, Salih HR et al. SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T cell recognition. Nat Immunol 2021; 22:74–85 [View Article] [PubMed]
    [Google Scholar]
  7. McMahan K, Yu J, Mercado NB, Loos C, Tostanoski LH et al. Correlates of protection against SARS-CoV-2 in rhesus macaques. Nature 2021; 590:630–634 [View Article] [PubMed]
    [Google Scholar]
  8. Lineburg KE, Grant EJ, Swaminathan S, Chatzileontiadou DSM, Szeto C et al. CD8+ T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope cross-react with selective seasonal coronaviruses. Immunity 2021; 54:1055–1065 [View Article] [PubMed]
    [Google Scholar]
  9. Schmidt KG, Nganou-Makamdop K, Tenbusch M, El Kenz B, Maier C et al. SARS-CoV-2-seronegative subjects target CTL Epitopes in the SARS-CoV-2 nucleoprotein cross-reactive to common cold coronaviruses. Front Immunol 2021; 12:627568 [View Article] [PubMed]
    [Google Scholar]
  10. Koutsakos M, Illing PT, Nguyen THO, Mifsud NA, Crawford JC et al. Human CD8+ T cell cross-reactivity across influenza A, B and C viruses. Nat Immunol 2019; 20:613–625 [View Article] [PubMed]
    [Google Scholar]
  11. Grifoni A, Weiskopf D, Ramirez SI, Mateus J, Dan JM et al. Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Cell 2020; 181:1489–1501 [View Article] [PubMed]
    [Google Scholar]
  12. Reynisson B, Alvarez B, Paul S, Peters B, Nielsen M et al. NetMHCpan-4.1 and NetMHCIIpan-4.0: improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data. Nucleic Acids Res 2020; 48:W449–W454 [View Article] [PubMed]
    [Google Scholar]
  13. Braun J, Loyal L, Frentsch M, Wendisch D, Georg P et al. SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19. Nature 2020; 587:270–274 [View Article] [PubMed]
    [Google Scholar]
  14. Mateus J, Grifoni A, Tarke A, Sidney J, Ramirez SI et al. Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans. Science 2020; 370:89–94 [View Article] [PubMed]
    [Google Scholar]
  15. Bonifacius A, Tischer-Zimmermann S, Dragon AC, Gussarow D, Vogel A et al. COVID-19 immune signatures reveal stable antiviral T cell function despite declining humoral responses. Immunity 2021; 54:340–354 [View Article] [PubMed]
    [Google Scholar]
  16. Rydyznski Moderbacher C, Ramirez SI, Dan JM, Grifoni A, Hastie KM et al. Antigen-specific adaptive immunity to SARS-CoV-2 in acute COVID-19 and associations with age and disease severity. Cell 2020; 183:996–1012 [View Article] [PubMed]
    [Google Scholar]
  17. Tarke A, Sidney J, Kidd CK, Dan JM, Ramirez SI et al. Comprehensive analysis of T cell immunodominance and immunoprevalence of SARS-CoV-2 epitopes in COVID-19 cases. Cell Rep Med 2021; 2:100204 [View Article] [PubMed]
    [Google Scholar]
  18. Sekine T, Perez-Potti A, Rivera-Ballesteros O, Strålin K, Gorin J-B et al. Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19. Cell 2020; 183:158–168 [View Article] [PubMed]
    [Google Scholar]
  19. Peng Y, Mentzer AJ, Liu G, Yao X, Yin Z et al. Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19. Nat Immunol 2020; 21:1336–1345 [View Article] [PubMed]
    [Google Scholar]
  20. Madhi SA, Baillie V, Cutland CL, Voysey M, Koen AL et al. Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant. N Engl J Med 2021; 384:1885–1898 [View Article] [PubMed]
    [Google Scholar]
  21. Wall EC, Wu M, Harvey R, Kelly G, Warchal S et al. Neutralising antibody activity against SARS-CoV-2 VOCs B.1.617.2 and B.1.351 by BNT162b2 vaccination. Lancet 2021; 397:2331–2333 [View Article] [PubMed]
    [Google Scholar]
  22. Shrotri M, Navaratnam AMD, Nguyen V, Byrne T, Geismar C et al. Spike-antibody waning after second dose of BNT162b2 or ChAdOx1. Lancet 2021; 398:385–387 [View Article] [PubMed]
    [Google Scholar]
  23. Lee WS, Wheatley AK, Kent SJ, DeKosky BJ. Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies. Nat Microbiol 2020; 5:1185–1191 [View Article] [PubMed]
    [Google Scholar]
  24. Wang Q, Zhang L, Kuwahara K, Li L, Liu Z et al. Immunodominant SARS coronavirus epitopes in humans elicited both enhancing and neutralizing effects on infection in non-human primates. ACS Infect Dis 2016; 2:361–376 [View Article] [PubMed]
    [Google Scholar]
  25. Soresina A, Moratto D, Chiarini M, Paolillo C, Baresi G et al. Two X-linked agammaglobulinemia patients develop pneumonia as COVID-19 manifestation but recover. Pediatr Allergy Immunol 2020; 31:565–569 [View Article] [PubMed]
    [Google Scholar]
  26. Tan AT, Linster M, Tan CW, Le Bert N, Chia WN et al. Early induction of functional SARS-CoV-2-specific T cells associates with rapid viral clearance and mild disease in COVID-19 patients. Cell Rep 2021; 34:108728 [View Article] [PubMed]
    [Google Scholar]
  27. Xu B, Fan C-Y, Wang A-L, Zou Y-L, Yu Y-H et al. Suppressed T cell-mediated immunity in patients with COVID-19: A clinical retrospective study in Wuhan, China. J Infect 2020; 81:e51–e60 [View Article] [PubMed]
    [Google Scholar]
  28. Mazzoni A, Salvati L, Maggi L, Capone M, Vanni A et al. Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent. J Clin Invest 2020; 130:4694–4703 [View Article] [PubMed]
    [Google Scholar]
  29. Bacher P, Rosati E, Esser D, Martini GR, Saggau C et al. Low-avidity CD4+ T cell responses to SARS-CoV-2 in unexposed individuals and humans with severe COVID-19. Immunity 2020; 53:1258–1271 [View Article] [PubMed]
    [Google Scholar]
  30. Diao B, Wang C, Tan Y, Chen X, Liu Y et al. Reduction and functional exhaustion of T cells in patients with coronavirus disease 2019 (COVID-19). Front Immunol 2020; 11:827. [View Article] [PubMed]
    [Google Scholar]
  31. Le Bert N, Tan AT, Kunasegaran K, Tham CYL, Hafezi M et al. SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature 2020; 584:457–462 [View Article] [PubMed]
    [Google Scholar]
  32. Ferretti AP, Kula T, Wang Y, Nguyen DMV, Weinheimer A et al. Unbiased screens show CD8+ T cells of COVID-19 patients recognize shared epitopes in SARS-CoV-2 that largely reside outside the spike protein. Immunity 2020; 53:1095–1107 [View Article] [PubMed]
    [Google Scholar]
  33. Saini SK, Hersby DS, Tamhane T, Povlsen HR, Amaya Hernandez SP et al. SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8+ T cell activation in COVID-19 patients. Sci Immunol 2021; 6:58 [View Article] [PubMed]
    [Google Scholar]
  34. Kusnadi A, Ramírez-Suástegui C, Fajardo V, Chee SJ, Meckiff BJ et al. Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8+ T cells. Sci Immunol 2021; 6:55 [View Article] [PubMed]
    [Google Scholar]
  35. Bertoletti A, Tan AT, Le Bert N. The T-cell response to SARS-CoV-2: kinetic and quantitative aspects and the case for their protective role. Oxford Open Immunology 2021; 2:iqab006 [View Article]
    [Google Scholar]
  36. Havenar-Daughton C, Carnathan DG, Torrents de la Peña A, Pauthner M, Briney B et al. Direct probing of germinal center responses reveals immunological features and bottlenecks for neutralizing antibody responses to HIV Env trimer. Cell Rep 2016; 17:2195–2209 [View Article] [PubMed]
    [Google Scholar]
  37. Mathew D, Giles JR, Baxter AE, Oldridge DA, Greenplate AR et al. Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science 2020; 369:eabc8511 [View Article] [PubMed]
    [Google Scholar]
  38. Abdelmageed MI, Abdelmoneim AH, Mustafa MI, Elfadol NM, Murshed NS et al. Design of a multiepitope-based peptide vaccinMultiepitope-Based Peptide Vaccine against the E protein of huProtein of Human COVID-19: An immunoinformatics appImmunoinformatics Approach. Biomed Res Int 20202683286 [View Article] [PubMed]
    [Google Scholar]
  39. Tazehkand MN, Hajipour O. Evaluating the vaccine potential of a tetravalent fusion protein against coronavirus (COVID-19). J Vaccines Vaccin 2020; 11:411
    [Google Scholar]
  40. Meyer-Olson D, Shoukry NH, Brady KW, Kim H, Olson DP et al. Limited T cell receptor diversity of HCV-specific T cell responses is associated with CTL escape. J Exp Med 2004; 200:307–319 [View Article] [PubMed]
    [Google Scholar]
  41. Nikolich-Zugich J, Slifka MK, Messaoudi I. The many important facets of T-cell repertoire diversity. Nat Rev Immunol 2004; 4:123–132 [View Article] [PubMed]
    [Google Scholar]
  42. Chang C-M, Feng P-H, Wu T-H, Alachkar H, Lee K-Y et al. Profiling of T cell repertoire in SARS-CoV-2-infected COVID-19 patients between mild disease and pneumonia. J Clin Immunol 2021; 41:1131–1145 [View Article] [PubMed]
    [Google Scholar]
  43. Fuller MJ, Zajac AJ. Ablation of CD8 and CD4 T cell responses by high viral loads. J Immunol 2003; 170:477–486 [View Article] [PubMed]
    [Google Scholar]
  44. Swanson PA, Padilla M, Hoyland W, McGlinchey K, Fields PA et al. T-cell mediated immunity after AZD1222 vaccination: A polyfunctional spike-specific Th1 response with a diverse TCR repertoire. medRxiv 2021 [View Article] [PubMed]
    [Google Scholar]
  45. Lind A, Sommerfelt M, Holmberg JO, Baksaas I, Sørensen B et al. Intradermal vaccination of HIV-infected patients with short HIV Gag p24-like peptides induces CD4 + and CD8 + T cell responses lasting more than seven years. Scand J Infect Dis 2012; 44:566–572 [View Article] [PubMed]
    [Google Scholar]
  46. Malonis RJ, Lai JR, Vergnolle O. Peptide-based vaccines: current progress and future challenges. Chem Rev 2020; 120:3210–3229 [View Article] [PubMed]
    [Google Scholar]
  47. Pollard RB, Rockstroh JK, Pantaleo G, Asmuth DM, Peters B et al. Safety and efficacy of the peptide-based therapeutic vaccine for HIV-1, Vacc-4x: a phase 2 randomised, double-blind, placebo-controlled trial. Lancet Infect Dis 2014; 14:291–300 [View Article] [PubMed]
    [Google Scholar]
  48. Rostad CA, Anderson EJ. Optimism and caution for an inactivated COVID-19 vaccine. Lancet Infect Dis 2021; 21:581–582 [View Article] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.001698
Loading
/content/journal/jgv/10.1099/jgv.0.001698
Loading

Data & Media loading...

Supplements

Supplementary material 1

EXCEL

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error