Picture of the Favourable Immune Profile Induced by Anti-SARS-CoV-2 Vaccination

Abstract

COVID-19 pandemic has hit people's health, economy, and society worldwide. Great confidence in returning to normality has been placed in the vaccination campaign. The knowledge of individual immune profiles and the time required to achieve immunological protection is crucial to choose the best vaccination strategy. We compared anti-S1 antibody levels produced over time by BNT162b2 and AZD1222 vaccines and evaluated the induction of antigen-specific T-cells. A total of 2569 anti-SARS-CoV-2 IgG determination on dried blood spot samples were carried out, firstly in a cohort of 1181 individuals at random time-points, and subsequently, in an independent cohort of 88 vaccinated subjects, up to the seventeenth week from the first dose administration. Spike-specific T-cells were analysed in seronegative subjects between the two doses. AZD1222 induced lower anti-S1 IgG levels as compared to BNT162b2. Moreover, 40% of AZD1222 vaccinated subjects and 3% of BNT162b2 individuals resulted in seronegative during all the time-points, between the two doses. All these subjects developed antigen-specific T cells, already after the first dose. These results suggest that this test represents an excellent tool for a wide sero-surveillance. Both vaccines induce a favourable immune profile guaranteeing efficacy against severe adverse effects of SARS-CoV-2 infection, already after the first dose administration.

Keywords: SARS-CoV-2; anti-S1 IgG; spike-specific T-cells; vaccines.

Figure 1

Panel (A) dot plot of the four groups analysed: Red dots IgG ratio for AZD1222 vaccinated donors, blue dots for BNT162b2 vaccinated donors, white RNI donors, and green dots controls subjects. Blue dashed line shows the positivity cut-off ratio. Panel (B) shows the median and 95% CI of IgG ratio for the groups in the study with the same colour code of panel (A).

Figure 2

Panel (A,C) show the mean level after the first dose administration (black line) of vaccines and the standard deviation between the IgG level (represented by the dashed red line) in BNT162b2 and AZD1222 vaccine, respectively. Panel (B,D) show the functional boxplot for BNT162b2 and AZD1222 IgG levels, respectively. The purple areas highlight the amplitude of 50% of the most central observation while the two outer blue curves correspond to the maximum and minimum curve of the dataset.

Figure 3

Panel (A): Beanplot of anti-S1 IgG levels after BNT162b2 vaccine administration. Dashed grey line is the median of analyses, while the dashed blue line indicates the cut-off of positivity. Panel (B): Beanplot of anti-S1 IgG levels after AZD1222 vaccine administration. Dashed grey line shows the median of analyses, while dashed red line indicates the cut-off of positivity. Panel (C,D): Frequency of positives patients in percentages. Blue bars represent the BNT162b2 vaccine (Panel (C)), while Red bars show the AZD1222 vaccine (Panel (D)). Dashed black vertical line indicates the time of the second dose vaccine administration in all panels.

Figure 4

IgG ratio at 21 days of vaccines administration for both vaccines before and after the second dose administration. Kruskal–Wallis tests shows p value < 0.0001 (indicated with ***) for each comparison with the exception of II dose AZD1222 vs. first dose of BNT162b2. The figure shows as the second dose of AZD1222 results in an IgG ratio similar to the first dose of BNT162b2 (no significance of Kruskal–Wallis test).

Figure 5

SARS-CoV-2-specific T cells in anti-S1 IgG seronegative and seropositive AZD1222 vaccinated donors. Frequencies of CD8+ or CD4+ T cells expressing T-cell activation markers (A,B) and producing antigen-specific cytokines (C,D) are shown in SARS-CoV-2 unexposed healthy donors who never received any anti-SARS-CoV-2 vaccine (CTRL), in anti-S1 IgG seronegative (anti-S1 IgG-) and seropositive (anti-S1 IgG+) donors vaccinated with a single dose of AZD1222, in the whole cohort of donors after a single dose of the AZD1222 vaccine administration (I dose AZD1222) and in a group of AZD1222 fully vaccinated donors. Frequencies were obtained by subtracting to the values of the stimulated samples the background produced by the related unstimulated tube. Individual data points are represented as scatter dot plots with lines showing the median value. Significance was calculated using non-parametric Mann–Whitney U-tests (two-tailed). (E) Pie charts show the expression of cytokine combinations from CD4+ and CD8+ T cells anti-S1 IgG seronegative and seropositive donors vaccinated with a single dose of AZD1222. (F) The ROC curve represents the performance of flow cytometry analysis.