DOI QR코드

DOI QR Code

Comparison of Four T-cell Assays and Two Binding Antibody Assays in SARS-CoV-2 Vaccinees With or Without Omicron Breakthrough Infection

  • Yeon Ju Seo (Department of Laboratory Medicine, Seoul National University Hospital) ;
  • Inseong Oh (Department of Laboratory Medicine, College of Medicine, Seoul National University) ;
  • Minjeong Nam (Department of Laboratory Medicine, Korea University Anam Hospital) ;
  • Sue Shin (Department of Laboratory Medicine, College of Medicine, Seoul National University) ;
  • Eun Youn Roh (Department of Laboratory Medicine, College of Medicine, Seoul National University) ;
  • Eun Young Song (Department of Laboratory Medicine, Seoul National University Hospital)
  • Received : 2023.02.04
  • Accepted : 2023.06.09
  • Published : 2023.11.01

Abstract

Background: Several T-cell response assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are available; however, their comparability and correlations with antibody responses remain unclear. We compared four SARS-CoV-2 T-cell response assays and two anti-SARS-CoV-2 spike antibody assays. Methods: We enrolled 89 participants who had received a booster dose of the BNT162b2 vaccine after two doses of the ChAdOx1 or BNT162b2 vaccine. Fifty-six participants without breakthrough infection (BI) (ChAdOx1/BNT162b2 group: N=27; BNT162b2 group: N=29) and 33 with BI were included. We evaluated two whole-blood interferon-gamma release assays (IGRAs) (QuantiFERON and Euroimmun), T-SPOT.COVID, an in-house enzyme-linked immunospot (ELISPOT) assay (targeting the spike and nucleocapsid peptides of wild-type and Omicron SARS-CoV-2), Abbott IgG II Quant, and Elecsys Anti-S, using Mann-Whitney U, Wilcoxon signed-rank, and Spearman's correlation tests. Results: The correlations between the IGRAs and between the ELISPOT assays (ρ=0.60-0.70) were stronger than those between the IGRAs and ELISPOT assays (ρ=0.33-0.57). T-SPOT.COVID showed a strong correlation with Omicron ELISPOT (ρ=0.70). The anti-spike antibody assays showed moderate correlations with T-SPOT.COVID, Euroimmun IGRA, and ELISPOT (ρ=0.43-0.62). Correlations tended to be higher in the BI than in the noninfected group, indicating that infection induces a stronger immune response. Conclusions: T-cell response assays show moderate to strong correlations, particularly when using the same platform. T-SPOT.COVID exhibits potential for estimating immune responses to the Omicron variant. To accurately define SARS-CoV-2 immune status, both T-cell and B-cell response measurements are necessary.

Keywords

References

  1. WHO. The coronavirus (COVID-19) dashboard. https://covid19.who.int/ (Updated on Jan 2023)
  2. KDCA. Korea Disease and Control and Prevention Agency. COVID-19 vaccination. https://ncv.kdca.go.kr/vaccineStatus.es?mid=a11710000000 (Updated on Feb 2023) 10000000
  3. Planas D, Saunders N, Maes P, Guivel-Benhassine F, Planchais C, Buchrieser J, et al. Considerable escape of SARS-CoV-2 Omicron to antibody neutralization. Nature 2022;602:671-5. https://doi.org/10.1038/s41586-021-04389-z
  4. Liu L, Iketani S, Guo Y, Chan JF, Wang M, Liu L, et al. Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2. Nature 2022;602:676-81. https://doi.org/10.1038/s41586-021-04388-0
  5. GeurtsvanKessel CH, Geers D, Schmitz KS, Mykytyn AZ, Lamers MM, Bogers S, et al. Divergent SARS-CoV-2 Omicron-reactive T and B cell responses in COVID-19 vaccine recipients. Sci Immunol 2022;7:eabo2202. https://doi.org/10.1126/sciimmunol.abo2202
  6. Basile K, Rockett RJ, McPhie K, Fennell M, Johnson-Mackinnon J, Agius JE, et al. Improved neutralisation of the SARS-CoV-2 Omicron variant following a booster dose of Pfizer-BioNTech (BNT162b2) COVID-19 vaccine. Viruses 2022;14:2023. https://doi.org/10.3390/v14092023
  7. Liu J, Chandrashekar A, Sellers D, Barrett J, Jacob-Dolan C, Lifton M, et al. Vaccines elicit highly conserved cellular immunity to SARS-CoV-2 Omicron. Nature 2022;603:493-6. https://doi.org/10.1038/s41586-022-04465-y
  8. Gao Y, Cai C, Grifoni A, Müller TR, Niessl J, Olofsson A, et al. Ancestral SARS-CoV-2-specific T cells cross-recognize the Omicron variant. Nat Med 2022;28:472-6. https://doi.org/10.1038/s41591-022-01700-x
  9. Zuo J, Dowell AC, Pearce H, Verma K, Long HM, Begum J, et al. Robust SARS-CoV-2-specific T cell immunity is maintained at 6 months following primary infection. Nat Immunol 2021;22:620-6. https://doi.org/10.1038/s41590-021-00902-8
  10. Le Bert N, Chia WN, Wan WY, Teo AKJ, Chong SZ, Tan N, et al. Widely heterogeneous humoral and cellular immunity after mild SARS-CoV-2 infection in a homogeneous population of healthy young men. Emerg Microbes Infect 2021;10:2141-50. https://doi.org/10.1080/22221751.2021.1999777
  11. Bonnet B, Chabrolles H, Archimbaud C, Brebion A, Cosme J, Dutheil F, et al. Decline of humoral and cellular immune responses against SARS-CoV-2 6 months after full BNT162b2 vaccination in hospital healthcare workers. Front Immunol 2022;13:842912. https://doi.org/10.3389/fimmu.2022.842912
  12. Naranbhai V, Nathan A, Kaseke C, Berrios C, Khatri A, Choi S, et al. T cell reactivity to the SARS-CoV-2 Omicron variant is preserved in most but not all individuals. Cell 2022;185:1041-51.e6. https://doi.org/10.1016/j.cell.2022.01.029
  13. Brand I, Gilberg L, Bruger J, Garí M, Wieser A, Eser TM, et al. Broad T cell targeting of structural proteins after SARS-CoV-2 infection: high throughput assessment of T cell reactivity using an automated interferon gamma release assay. Front Immunol 2021;12:688436. https://doi.org/10.3389/fimmu.2021.688436
  14. Taus E, Hofmann C, Ibarrondo FJ, Hausner MA, Fulcher JA, Krogstad P, et al. Dominant CD8+ T cell nucleocapsid targeting in SARS-CoV-2 infection and broad spike targeting from vaccination. Front Immunol 2022;13:835830. https://doi.org/10.3389/fimmu.2022.835830
  15. Woldemeskel BA, Garliss CC, Aytenfisu TY, Johnston TS, Beck EJ, Dykema AG, et al. SARS-CoV-2-specific immune responses in boosted vaccine recipients with breakthrough infections during the Omicron variant surge. JCI Insight 2022;7;e159474. https://doi.org/10.1172/jci.insight.159474
  16. Uwamino Y, Kurafuji T, Takato K, Sakai A, Tanabe A, Noguchi M, et al. Dynamics of antibody titers and cellular immunity among Japanese healthcare workers during the 6 months after receiving two doses of BNT162b2 mRNA vaccine. Vaccine 2022;40:4538-43. https://doi.org/10.1016/j.vaccine.2022.06.016
  17. Kim JY, Lim SY, Park S, Kwon JS, Bae S, Park JY, et al. Immune responses to the ChAdOx1 nCoV-19 and BNT162b2 vaccines and to natural coronavirus disease 2019 infections over a 3-month period. J Infect Dis 2022;225:777-84. https://doi.org/10.1093/infdis/jiab579
  18. Strengert M, Becker M, Ramos GM, Dulovic A, Gruber J, Juengling J, et al. Cellular and humoral Immunogenicity of a SARS-CoV-2 mRNA vaccine in patients on haemodialysis. EBioMedicine 2021;70:103524. https://doi.org/10.1016/j.ebiom.2021.103524
  19. Malipiero G, Moratto A, Infantino M, D'Agaro P, Piscianz E, Manfredi M, et al. Assessment of humoral and cellular immunity induced by the BNT-162b2 SARS-CoV-2 vaccine in healthcare workers, elderly people, and immunosuppressed patients with autoimmune disease. Immunol Res 2021;69:576-83. https://doi.org/10.1007/s12026-021-09226-z
  20. Safont G, Latorre I, villar-Hernández R, Stojanovic Z, Marín A, Pérez-Cano C, et al. Measuring T-cell responses against SARS-CoV-2 is of utility for disease and vaccination management. J Clin Med 2022;11:5103. https://doi.org/10.3390/jcm11175103
  21. Primorac D, Brlek P, Matisic V, Molnar V, Vrdoljak K, Zadro R, et al. Cellular immunity-the key to long-term protection in individuals recovered from SARS-CoV-2 and after vaccination. Vaccines (Basel) 2022;10:442. https://doi.org/10.3390/vaccines10030442
  22. Hillus D, Schwarz T, Tober-Lau P, Vanshylla K, Hastor H, Thibeault C, et al. Safety, reactogenicity, and immunogenicity of homologous and heterologous prime-boost immunisation with ChAdOx1 nCoV-19 and BNT-162b2: a prospective cohort study. Lancet Respir Med 2021;9:1255-65. https://doi.org/10.1016/S2213-2600(21)00357-X
  23. Parry H, Bruton R, Stephens C, Brown K, Amirthalingam G, Otter A, et al. Differential immunogenicity of BNT162b2 or ChAdOx1 vaccines after extended-interval homologous dual vaccination in older people. Immun Ageing 2021;18:34. https://doi.org/10.1186/s12979-021-00246-9
  24. Schiffner J, Backhaus l, Rimmele J, Schulz S, Möhlenkamp T, Klemens JM, et al. Long-term course of humoral and cellular immune responses in outpatients after SARS-CoV-2 infection. Front Public Health 2021;9:732787. https://doi.org/10.3389/fpubh.2021.732787
  25. Wongpakaran N, Wongpakaran T, Wedding D, Gwet KL. A comparison of Cohen's Kappa and Gwet's AC1 when calculating inter-rater reliability coefficients: a study conducted with personality disorder samples. BMC Med Res Methodol 2013;13:61. https://doi.org/10.1186/1471-2288-13-61
  26. Gwet KL. Testing the difference of correlated agreement coefficients for statistical significance. Educ Psychol Meas 2016;76:609-37. https://doi.org/10.1177/0013164415596420
  27. Altman DG. Practical statistics for medical research. 1st ed. London: Chapman & Hall, 1991. p. 404.
  28. Salkind NJ. Statistics for people who hate statistics. 3rd ed. CA: Sage Publications, 2008. p. 132.
  29. Schmidt F, Muecksch F, Weisblum Y, Da Silva J, Bednarski E, Cho A, et al. Plasma neutralization of the SARS-CoV-2 Omicron variant. N Engl J Med 2022;386:599-601. https://doi.org/10.1056/NEJMc2119641
  30. Tarke A, Coelho CH, Zhang Z, Dan JM, Yu ED, Methot N, et al. SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron. Cell 2022;185:847-59.e11. https://doi.org/10.1016/j.cell.2022.01.015
  31. Bertoletti A, Le Bert N, Tan AT. SARS-CoV-2-specific T cells in the changing landscape of the COVID-19 pandemic. Immunity 2022;55:1764-78. https://doi.org/10.1016/j.immuni.2022.08.008
  32. Kim JA, Bang HI, Shin JW, Park Y, Kim S, Kim MY, et al. Immunogenicity of Third-dose BNT162b2 mRNA Vaccine Following Two Doses of ChAdOx1 in Health Care Workers: A Prospective Longitudinal Study. Ann Lab Med 2022;42:688-92. https://doi.org/10.3343/alm.2022.42.6.688