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. 2022 Oct 24;10(11):1784.
doi: 10.3390/vaccines10111784.

Healthcare Worker Study Cohort to Determine the Level and Durability of Cellular and Humoral Immune Responses after Two Doses of SARS-CoV-2 Vaccination

Chiara Dentone  1 , Daniela Fenoglio  2   3 , Marta Ponzano  4 , Matteo Cerchiaro  5 , Tiziana Altosole  2 , Diego Franciotta  6 , Federica Portunato  1 , Malgorzata Mikulska  1   5 , Lucia Taramasso  1 , Laura Magnasco  1 , Chiara Uras  2 , Federica Magne  1 , Francesca Ferrera  2 , Graziana Scavone  3 , Alessio Signori  4 , Antonio Vena  1 , Valeria Visconti  7 , Gilberto Filaci  2   3 , Alessandro Sette  8   9 , Alba Grifoni  8 , Antonio Di Biagio  1   5 , Matteo Bassetti  1   5
Affiliations

Healthcare Worker Study Cohort to Determine the Level and Durability of Cellular and Humoral Immune Responses after Two Doses of SARS-CoV-2 Vaccination

Chiara Dentone et al. Vaccines (Basel). .

Abstract

We prospectively studied immunological response against SARS-CoV-2 after vaccination among healthcare workers without (group A) and with previous infection (group B). The analyses were collected at T0 (before the BNT162b2), T1 (before the second dose), T2 and T6 (1 and 6 months after the second dose). For cellular immune response, the activation-induced cell marker assay was performed with CD4 and CD8 Spike peptide megapools expressed as Stimulation Index. For humoral immune response, we determined antibodies to Spike-1 and nucleocapsid protein. The linear mixed model compared specific times to T0. The CD4+ Spike response overall rate of change was significant at T1 (p = 0.038) and at T2 (p < 0.001), while decreasing at T6. For CD8+ Spike reactivity, the interaction between the time and group was significant (p = 0.0265), and the p value for group comparison was significant at the baseline (p = 0.0030) with higher SI in previously infected subjects. Overall, the anti-S Abs significantly increased from T1 to T6 compared to T0. The group B at T6 retained high anti-S titer (p < 0.001). At T6, in both groups we found a persistent humoral response and a high CD4+ T cell response able to cross recognize SARS-COV-2 variants including epsilon, even if not a circulating virus at that time.

Keywords: SARS-CoV-2; cellular and humoral immune responses; second dose; variants.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Outside the submitted work: C.D. has received speaker honoraria from Angelini, Novartis, Gilead, ViiV andShinogi. A.D.B. reports a hospital grant from Gilead and consultancy for ViiV, Janssen, MSD, Gilead and Abbvie. L.T. reports consultancy for ViiV, Gilead and Janssen. A. Sette is a consultant for Gritstone, Flow Pharma, CellCarta, Arcturus, Oxfordimmunotech and Avalia. M. B. serves on the scientific advisory boards for Angelini, AstraZeneca, Bayer, Cubist, Pfizer, Menarini, MSD, Nabriva, Paratek, Roche, Shionogi, Tetraphase, The Medicine Company and Astellas Pharma Inc, and has received funding for travel or speaker honoraria from Algorithm, Angelini, Astellas Pharma Inc., AstraZeneca, Cubist, Pfizer, MSD, Gilead Sciences, Menarini, Novartis, Ranbaxy and Teva. A.S. is a consultant for Gritstone Bio, Flow Pharma, Arcturus Therapeutics, ImmunoScape, CellCarta, Avalia, Moderna, Fortress, Repertoire and Astrazeneca. LJI has filed for patent protection for various aspects of T cell epitope and vaccine design work.

Figures

Figure 1
Figure 1
The overall rate of change over time for CD4+ T cell response to Spike megapools (MPS). The values were significant at T1 (p = 0.038) and at T2 (p < 0.001) compared to T0 with a decrease at T6 (p not significant). The data are expressed as Stimulation Index (SI), mean (standard deviation, SD) and median (interquartile range, IQR). The bolded line indicates the overall rate of change over time among the entire cohort of health workers.
Figure 2
Figure 2
The CD4+ T cell response to Spike peptide megapools (MPS) in the two groups of subjects. The data are expressed as Stimulation Index (SI), mean (standard deviation, SD) and median (interquartile range, IQR). p-value between the two groups is analyzed at each timepoints with Mann–Whitney test.
Figure 3
Figure 3
The CD8+ T cell response to Spike peptide megapools (MPS) in the two groups of subjects. The data are expressed as Stimulation Index (SI), mean (standard deviation, SD) and median (interquartile range, IQR). p-value between the two groups is analyzed with Mann–Whitney test at each timepoint.
Figure 4
Figure 4
Panel (A): The quantitative antibodies to Spike-1 protein (S AbS) in the two groups of subjects. Panel (B): The quantitative humoral immune response to nucleocapsid protein in the two groups of subjects. The values of quantitative anti-S antibodies (S Abs) are expressed using Binding Antibody Unit (BAU) as mean (standard deviation, SD) and median (interquartile range, IQR). The values of quantitative anti-N antibodies (N Abs) are expressed using COI (cutoff index). p-value between the two groups is analyzed at each timepoint with Mann–Whitney test.
Figure 4
Figure 4
Panel (A): The quantitative antibodies to Spike-1 protein (S AbS) in the two groups of subjects. Panel (B): The quantitative humoral immune response to nucleocapsid protein in the two groups of subjects. The values of quantitative anti-S antibodies (S Abs) are expressed using Binding Antibody Unit (BAU) as mean (standard deviation, SD) and median (interquartile range, IQR). The values of quantitative anti-N antibodies (N Abs) are expressed using COI (cutoff index). p-value between the two groups is analyzed at each timepoint with Mann–Whitney test.
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