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. 2024 Nov 29;12(12):1350.
doi: 10.3390/vaccines12121350.

Longitudinal Comparison of Three T-Cell Assays and Three Antibody Assays Against SARS-CoV-2 Following Homologous mRNA-1273/mRNA-1273/mRNA-1273 and Heterologous ChAdOx1/ChAdOx1/BNT162b2 Vaccination: A Prospective Cohort in Naïve Healthcare Workers

Hyeyoung Lee  1 , Geon Young Ko  2 , Jihyun Lee  2 , Hyunjoo Bae  2 , Ji Hyeong Ryu  3 , Jin Jung  3 , Hyunhye Kang  3   4 , Raeseok Lee  5   6 , Dong-Gun Lee  5   6 , Eun-Jee Oh  3   4
Affiliations

Longitudinal Comparison of Three T-Cell Assays and Three Antibody Assays Against SARS-CoV-2 Following Homologous mRNA-1273/mRNA-1273/mRNA-1273 and Heterologous ChAdOx1/ChAdOx1/BNT162b2 Vaccination: A Prospective Cohort in Naïve Healthcare Workers

Hyeyoung Lee et al. Vaccines (Basel). .

Abstract

Background: Cellular and humoral immunity are key to the immune response against SARS-CoV-2, but the comparability and correlation across different assays remain underexplored. This study compares three T-cell and three antibody assays in two vaccine groups. Methods: This prospective longitudinal cohort study involved 46 naïve healthcare workers: a total of 11 in the homologous mRNA-1273 group (three doses) and 35 in the heterologous ChAd group (two ChAd doses followed by a BNT booster). Blood samples were collected at five time points. Cellular immunity was assessed using ELISPOT and two commercial interferon-gamma release assays: (IGRA)-QuantiFERON SARS-CoV-2 (QF) and Covi-FERON ELISA (CoVF). Humoral immunity was evaluated using total and IgG antibody assays and a surrogate virus neutralization test. Results: The mRNA-1273 group exhibited stronger and more consistent responses than the ChAd group. The correlations between ELISPOT and IGRA varied from weak to moderate (ρ = 0.300-0.410), while QF-IGRA and CoVF-IGRA showed stronger correlations (ρ = 0.700-0.737). The ELISPOT assay showed substantial agreement with QF [Ag2]-IGRA (k = 0.697-0.774) and CoVF [O-sp]-IGRA (k = 0.641-0.718), and an 80.4% agreement rate (k = 0.608) was found between the QF [Ag2]- and CoVF [O-sp]-IGRA tests. Three antibody assays demonstrated very strong correlations with each other and substantial to near-perfect agreement with ELISPOT (k = 0.866-0.949), QF [Ag2]-IGRA (k = 0.807-0.831), and CoVF [O-sp]-IGRA (k = 0.753-0.777). Conclusions: SARS-CoV-2-specific cellular and antibody responses vary by platform and vaccine type, highlighting the importance of measuring both T-cell and B-cell responses using multiple assays to comprehensively assess immune status.

Keywords: ELISPOT; SARS-CoV-2; cellular response; humoral response; interferon-gamma release assay; vaccine.

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Conflict of interest statement

The authors declare no conflicts of interest. SD biosensor (Korea) had no role in the design of this study, data collection, data analyses, data interpretation, writing of the manuscript, or decision to publish the results.

Figures

Figure 1
Figure 1
Longitudinal SARS-CoV-2-specific ELISPOT responses against three peptide pools in each vaccine group. SARS-CoV-2-specific ELISPOT responses against S (A), S1 (B), and S+ (C) peptides along with the corresponding positive rates are presented. The Mann–Whitney test was used for the significant changes over the study period. * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001.
Figure 2
Figure 2
Longitudinal changes in SARS-CoV-2-specific interferon-gamma release assays. SARS- CoV-2-specific cellular responses were measured with the Ag1 (A) and Ag2 (B) tubes in QuantiFERON and the original spike (C) and variant spike (D) tubes in Covi-FERON. The Mann–Whitney test was used for the significant changes over the study period. Positive rates were compared using the chi-square or Fisher’s exact test. * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001.
Figure 3
Figure 3
Longitudinal changes in three antibody assays. SARS-CoV-2-spike-specific total binding antibody levels (A), IgG antibody levels (B), and neutralizing antibody levels (C) from the SARS-CoV-2 surrogate virus neutralization test are presented. The assay cut-off is shown as a horizontal dashed line. The Mann–Whitney test was used for the significant changes over the study period. * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001.
Figure 4
Figure 4
Correlations between SARS-CoV-2 T-cell assays using the same platforms but different peptide stimulations. Correlation between three peptides of ELISPOT (A), correlation between Ag1 tube and Ag2 tube in QF-IGRA (B), and correlation between O-sp tube and V-sp tube in CoVF-IGRA (C) are presented. **** p < 0.0001.
Figure 5
Figure 5
Correlation between SARS-CoV-2-specific ELISPOT and IGRAs. Correlation between ELISPOT and QF-IGRA (A), correlation between ELISPOT and CoVF-IGRA (B), correlation between Ag1 tube in QF-IGRA and CoVF-IGRA (C), and correlation between Ag2 tube in QF-IGRA and CoVF-IGRA (D) are presented.
Figure 6
Figure 6
Correlogram of SARS-CoV-2-specific cellular and humoral response measured by ELISPOT, IGRA, and antibody assay and neutralizing antibody assay in total (A), homologous mRNA group (B), and heterologous ChAd group (C). The intensity of the color represents Spearman’s rank correlation coefficient.
Figure 7
Figure 7
Correlation between SARS-CoV-2-specific antibody assays and three cellular assays. (A) Correlation between the three antibody assays and ELISPOT assay. (B) Correlation between the three assays and QF-IGRA assay. (C) Correlation between the three assays and CoVF-IGRA assay.
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