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. 2022 Dec;97(12):E457-E461.
doi: 10.1002/ajh.26729. Epub 2022 Sep 24.

Increased CD8 T-cell immunity after COVID-19 vaccination in lymphoid malignancy patients lacking adequate humoral response: An immune compensation mechanism?

Lara S Boerenkamp  1 , Cilia R Pothast  2 , Romy C Dijkland  2 , Kayleigh van Dijk  2 , Gwendolyn N Y van Gorkom  1 , Inge H M van Loo  3 , Lotte Wieten  4 , Constantijn J M Halkes  5 , Mirjam H M Heemskerk  2 , Catharina H M J Van Elssen  1
Affiliations

Increased CD8 T-cell immunity after COVID-19 vaccination in lymphoid malignancy patients lacking adequate humoral response: An immune compensation mechanism?

Lara S Boerenkamp et al. Am J Hematol. 2022 Dec.
No abstract available

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Humoral and spike‐specific CD4+ and CD8+ T‐cell responses after mRNA vaccination in patients with CLL (purple), aggressive NHL (green), indolent NHL (pink) or MM (red). Response evaluation at different time points (2 weeks, 3 months, and 6 months) after initial complete vaccination, which for mRNA‐1273 and BNT162b consisted of two vaccination doses, administered within a 4–5 week interval. Data for patients with CLL are shown in blue, for aggressive NHL in green, for indolent NHL in purple and, for MM in red. Anti‐SARS‐CoV‐2 Spike antibodies were measured using anti‐SARS‐CoV‐2 S immunoassay. Spike‐specific T‐cell responses were measured by thawing PBMCs and stimulating them with a spike peptide pool for 16 h, and afterwards, samples were analyzed by flow cytometry using various markers. Values were corrected for background measured in DMSO. In (B–H), each dot represents a patient; seronegative patients are depicted as circles and seropositive patients are depicted as darker triangles. (A) Response rates 2 weeks after complete vaccination, serological response rate was based on the percentage of patients with adequate anti‐SARS‐CoV‐2 spike Ig (>250 BAU/ml). CD4+ T‐cell response was the percentage of patients with >0.05% of spike‐specific CD4+ T‐cells (CD137+ and/or CD154+) within the total CD4+ population and CD8+ T‐cell response was the percentage of patients with >0.005% of spike‐specific CD8+ T‐cells (CD69+ and/or CD137+ and IFN‐γ+ and/or TNF‐α+) and/or Spike/HLA‐tetramer positive CD8+ T‐cells within the total CD8+ population. All proportions were stratified based on hematological disorder and compared to expected population proportions of 99% for serological response, 100% for CD4+ T‐cell response, and 50% for CD8+ T‐cell response (shown as dotted lines in the figure) using one sample binomial testing. Clopper‐Pearson method was used to estimate 95% confidence intervals. (B) Percentage of spike‐specific CD4+ T‐cells of total CD4+ T‐cells measured before and after vaccination. Spike‐specific CD4+ T‐cells were defined as CD4+ T‐cells expressing CD137+and/or CD154+ after stimulation with SARS‐CoV‐2 Spike peptides. Dotted line represents threshold of 0.05%. Black horizontal line represents median. Kruskal–Wallis testing does not show significant difference between hematologic disorders at 2 weeks, 3, or 6 months (p = .526, p = .319, .227). Wilcoxon test shows a significant increase in percentage of spike‐specific CD4+ T‐cells 2 weeks after vaccination for CLL, aggressive NHL and indolent NHL (p = .0078, .0156, .0313) compared to pre vaccination, MM was not tested due to lack of sufficient samples. (C) Percentage of spike‐specific CD8+ T‐cells of total CD8+ T‐cells measured before and after vaccination. Spike‐specific CD8+ T‐cells were defined as CD8+ T‐cells having a expressing CD69+and/or CD137+ and IFN‐γ+ and/or TNF‐α+ after SARS‐CoV2 spike peptide stimulation. Dotted line represents threshold of 0.005%. Black horizontal line represents median. Kruskal–Wallis testing does not show significant difference between hematologic disorders at 2 weeks, 3, or 6 months (p = .369, .921, .082). Wilcoxon test shows no significant increase in spike‐specific CD8+ T‐cell response 2 weeks after vaccination for CLL, aggressive and indolent NHL (p = .195, .250, .922) compared to pre‐vaccination, MM was not tested due to lack of sufficient samples. (D) Percentage of Spike/HLA‐tetramer positive CD8+ T‐cells of total CD8+ T‐cells measured before and after vaccination. Dotted line represents threshold of 0.005%. Black horizontal line represents median. Kruskal–Wallis testing does not show significant difference between hematologic disorders at 2 weeks, 3, or 6 months (p = .146, .225, .188). Wilcoxon test shows no significant increase in tetramer positive CD8+ T‐cell responses 2 weeks after vaccination for CLL, aggressive and indolent NHL (p = .063, .063, .094) compared to pre‐vaccination, MM was not tested due to lack of sufficient samples. (E) Percentage of patients with spike‐specific CD4+ or CD8+ T‐cell responses in adequately seroconverted (Ig+) or seronegative (Ig−) patients. Significance was tested by Chi square test (CD4+ p = .640, CD8+ p = .143). (F) Frequency of spike‐specific CD4+ or CD8+ T‐cells in adequately seroconverted (Ig+) or seronegative (Ig−) patients. Significance was tested by Mann–Whitney U tests (CD4+ p = .332, CD8+ p = .007, tetramer p = .21). (G) Percentage of patients with a spike‐specific CD4+ or CD8+ T‐cell response split by age under or above 68 years. Significance was tested by Chi square test (CD4+ p = .033, CD8+ p = .001). (H) Percentage of spike‐specific CD8+ T‐cells (CD69+and/or CD137+ and IFN‐γ+ and/or TNF‐α+) of total CD8+ T‐cells (y‐axis) plotted against percentage of spike‐specific CD4+ T‐cells (CD137+and/or CD154+) of total CD4+ T‐cells (x‐axis). All patients at timepoint 2 weeks or 3 months, independent of cohort, are shown in the figure and dark triangles depict patients with an adequate anti‐spike antibody response. Dotted lines either represent threshold for spike‐specific CD8+ T‐cell response on y‐axis of 0.005% or spike‐specific CD4+ T‐cell response on x‐axis of 0.05%. ns, not significant; *p < .05; **p < .01 or ***p < .001. PRE, before vaccination; 2W, 2 weeks after complete vaccination; 3M, 3 months after complete vaccination; 6M, 6 months after complete vaccination.
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References

    1. Jiménez M, Roldán E, Fernández‐Naval C, et al. Cellular and humoral immunogenicity of the mRNA‐1273 SARS‐CoV‐2 vaccine in patients with hematologic malignancies. Blood Adv. 2022;6(3):774‐784. - PMC - PubMed
    1. Moss P. The T cell immune response against SARS‐CoV‐2. Nat Immunol. 2022;23(2):186‐193. - PubMed
    1. Bange EM, Han NA, Wileyto P, et al. CD8+ T cells contribute to survival in patients with COVID‐19 and hematologic cancer. Nat Med. 2021;27(7):1280‐1289. - PMC - PubMed
    1. Sahin U, Muik A, Derhovanessian E, et al. COVID‐19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature. 2020;586(7830):594‐599. - PubMed
    1. Marasco V, Carniti C, Guidetti A, et al. T‐cell immune response after mRNA SARS‐CoV‐2 vaccines is frequently detected also in the absence of seroconversion in patients with lymphoid malignancies. Br J Haematol. 2022;196(3):548‐558. - PMC - PubMed