Evaluation of humoral and cellular response to four vaccines against COVID-19 in different age groups: A longitudinal study

Abstract

To date there has been limited head-to-head evaluation of immune responses to different types of COVID-19 vaccines. A real-world population-based longitudinal study was designed with the aim to define the magnitude and duration of immunity induced by each of four different COVID-19 vaccines available in Italy at the time of this study. Overall, 2497 individuals were enrolled at time of their first vaccination (T0). Vaccine-specific antibody responses induced over time by Comirnaty, Spikevax, Vaxzevria, Janssen Ad26.COV2.S and heterologous vaccination were compared up to six months after immunization. On a subset of Comirnaty vaccinees, serology data were correlated with the ability to neutralize a reference SARS-CoV-2 B strain, as well as Delta AY.4 and Omicron BA.1. The frequency of SARS-CoV-2-specific CD4+ T cells, CD8+ T cells, and memory B cells induced by the four different vaccines was assessed six months after the immunization. We found that mRNA vaccines are stronger inducer of anti-Spike IgG and B-memory cell responses. Humoral immune responses are lower in frail elderly subjects. Neutralization of the Delta AY.4 and Omicron BA.1 variants is severely impaired, especially in older individuals. Most vaccinees display a vaccine-specific T-cell memory six months after the vaccination. By describing the immunological response during the first phase of COVID-19 vaccination campaign in different cohorts and considering several aspects of the immunological response, this study allowed to collect key information that could facilitate the implementation of effective prevention and control measures against SARS-CoV-2.

Keywords: B-cell memory; COVID-19; cell-mediated immunity; serology; vaccines.

Figure 1

Kinetics of COVID-19 vaccine-induced IgG over time. The trajectories of serum anti-trimeric-Spike IgG (BAU/ml) for all the subjects analysed, stratified by type of vaccine or previous COVID-19 diagnosis are shown (thin lines). Mean values in each group are indicated (thick lines). The dotted line represents the positivity cut-off of the serological assay (33.8 BAU/ml).

Figure 2

Microneutralization titers of T1 and T2 sera from COVID-19 naïve subjects vaccinated with Comirnaty. Sera from healthy adults (A) and frail elderly subjects (B) vaccinated with the Comirnaty vaccine were used to neutralize reference SARS-CoV-2 strain (B) and a Delta strain (AY.4). Individual MNT are reported together with median values. Non-neutralizing sera (MNT<8) are placed on the x-axis; frequencies of non-neutralizing sera are indicated below the graphs. Statistical differences among strains were calculated by the Kruskall-Wallis test; differences among time-points were calculated with the Wilcoxon test.

Figure 3

Microneutralization titers of T2 sera from COVID-19 naïve subjects vaccinated with Comirnaty. Sera from healthy adults (A) and frail elderly subjects (B) vaccinated with the Comirnaty vaccine were used to neutralize reference SARS-CoV-2 strain (B), a Delta strain (AY.4) and an Omicron strain (BA.1). Individual MNT are reported together with median values. Non-neutralizing sera (MNT<8) are placed on the x-axis; frequencies of non-neutralizing sera are indicated below the graphs. Statistical differences among strains were calculated by the Kruskall-Wallis test.

Figure 4

Correlation between anti-trimeric Spike IgG titers and serum neutralization activity. Linear regression correlating the levels of anti-trimeric S IgG with MNT values against reference SARS-CoV-2 strain (B), a Delta strain (AY.4) and an Omicron (BA.1). r and P values are shown.

Figure 5

T-cell mediated immune response in COVID-19 vaccinees 6 months after first immunization. The frequencies of CD4+ and CD8+ T cells producing IFN-γ, TNFα and IL-12 in healthy adults (A, B) and frail elderly subjects (C, D) in response to in vitro stimulation with Spike are shown as total cytokine response. Statistical differences among types of vaccine were calculated by the Wilcoxon test. Pie diagrams show the frequencies of non-responding T cells or T cells producing 1 to 3 cytokines simultaneously.

Figure 6

Anti-Spike specific B-cell memory responses in COVID-19 vaccinees 6 months after first immunization. The frequencies of memory B cells displaying high specificity towards the ancestral Spike antigen and the frequencies of ancestral Spike-specific memory B cells highly specific towards Delta (B.1.617.2) Spike antigen in healthy adults (A, B) and frail elderly subjects (C, D) are shown. Statistical differences were calculated by the Wilcoxon test.