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. 2023 Feb 16;4(3):191–215.e9. doi: 10.1016/j.medj.2023.02.004

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© 2023 The Authors. Published by Elsevier Inc.

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Comparison of cytokine response at 6 months after dose 2 against ancestral strain and Omicron BA.1 variant according to infection status

Longitudinal comparison of T cell and B cell responses against ancestral strain and Omicron BA.1 variant according to vaccine regimen and infection status.

(A) Comparison of percentage IFNγ, TNF, and IL-2-positive CD4 T cells against ancestral strain and Omicron BA.1 variant by ICS of cryopreserved PBMCs in either infection-naive participants or participants with hybrid immunity. Box plots represent the median and IQR and whiskers represent 1.5× the IQR.

(B) Comparison of percentage IFNγ, TNF, and IL-2-positive CD8 T cells against ancestral strain and Omicron BA.1 variant by ICS of PBMCs in either infection-naive participants or participants with hybrid immunity. Box plots represent the median and IQR and whiskers represent 1.5× the IQR.

(C and D) Pairwise comparison of T cell responses to spike from ancestral strain and Omicron BA.1 variant from PBMCs by IFNγ ELISpot assay (C) in participants 6 months after primary vaccine course (two doses of BNT162b2 or AstraZeneca), n = 215, and (D) 1 month after third BNT162b2 vaccine dose, n = 175. Displayed are responses to peptide pools representing the sum of S1 and S2 units of S from ancestral strain and Omicron variant.

(E) Pairwise comparison of IFNγ ELISpot responses in a subset of participants (n = 36) to only the 51 out of 178 peptides spanning spike that have mutations in Omicron BA.1 compared with the ancestral strain.

(F) T cell responses to spike from ancestral strain and Omicron BA.1, BA.2, and BA.4/5 variants in PBMCs from naive (n = 28) and hybrid immune (n = 46) donors by IFNγ ELISpot assay. Horizontal lines represent the median.

(G–I) (G) Pairwise comparison of B cell responses to S in ancestral strain and Omicron BA.1 variant from PBMCs in participants 1 month after vaccine dose 2 (n = 12); (H) 6 months post second vaccine dose (n = 43); (I) 1 month after third vaccine dose (n = 80). Orange circles, responses against Victoria variant; blue circles, responses against Omicron BA.1 variant. Displayed are responses to peptide pools representing S1 and S2 units of S from ancestral and Omicron variants. ELISpot values are expressed as antibody SFU/10⁶ PBMCs. Horizontal lines represent median values. Comparisons between responses to ancestral and Omicron variants were made using Wilcoxon matched-pairs signed-rank test, with two-tailed p values of significant differences (p ≤ 0.05) shown above linking line.