Real-world monitoring of BNT162b2 vaccine-induced SARS-CoV-2 B and T cell immunity in naive healthcare workers: a prospective single center study

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing COVID-19 pandemic. To prevent the massive COVID-19 burden, several vaccination campaigns were initiated. We performed a single center observational trial to evaluate adaptive immunity in naive healthcare workers upon BNT162b2 vaccination. Methods: Serological analysis was performed through conventional immunoassays. Antibody functionality was analyzed via in vitro neutralization assays. Circulating receptor-binding domain (RBD) specific B cells were assessed via flowcytometry. The induction of SARS-CoV-2 specific T cells was investigated through interferon-γ release assay combined with flowcytometric profiling of activated CD4 and CD8 T cells. Results: Three months after vaccination, all but one of the subjects (N = 31) displayed vaccine-induced neutralizing antibodies. In 10 out of 31 subjects, circulating RBD specific B cells were found of which the rate showed moderate correlation to serological parameters. Specific interferon-γ release was present in all subjects and correlated with the significant upregulation of CD69 on CD4+ and CD8+ T cells and CD40L on CD4+ T cells. Interestingly, no relation was found between B and T cell parameters. In addition, one symptomatic breakthrough infection with the SARS-CoV-2 alpha variant of concern was reported. Conclusion: Three months post vaccination, both humoral and cellular immune responses are detectable in all but one participant. No correlation was found between the magnitude of both B and T cell responses.

High Incidence of SARS-CoV-2 Variant of Concern Breakthrough Infections Despite Residual Humoral and Cellular Immunity Induced by BNT162b2 Vaccination in Healthcare Workers: A Long-Term Follow-Up Study in Belgium

“…SARS-CoV-2-specific T cell activity was assessed via stimulation of the T cells using the EUROIMMUN Quan-T-Cell SARS-CoV-2 assay (cat Nr. ET 2606-3003) that was performed according to the manufacturer's instructions adapted as described earlier [22]. First, 500 µL of heparinized whole blood was transferred into three different tubes (BLANK, COV2 and STIM) followed by a 20-24 h incubation step at 37 • C after inverting these tubes 6 times.…”

“…Next, a whole blood staining was performed on the reconstituted samples. In summary, T cell staining was performed on 150 µL of the reconstituted fractions [22]. Following incubation for 30 min at 4 • C, 3 mL of red blood cell (RBC) lysis buffer (BD FACS TM lysing solution, BD Biosciences, Franklin Lakes, NJ, USA) was added for 5 min at RT to allow lysis of the RBC fraction.…”

“…Hence, the large (inter-)national vaccination campaigns presented a unique opportunity to study the nucleic acid-based vaccine-induced immune reaction and longevity. Indeed, a myriad of reports were published describing both SARS-CoV-2-specific B cell or T cell reactions after partial (i.e., single dose) or full vaccination (i.e., two doses) with either the BNT162b2 or mRNA-1273 vaccine within several study groups (e.g., healthcare personnel and immunocompromised patients) up to 6 months after vaccination [16][17][18][19][20][21][22]. However, long-term documentation of integrated humoral and cellular immunity is scarce, in particular in healthy SARS-CoV-2-naive subjects.…”

“…Other reports that did perform long-term follow-up monitoring mostly focused on a specific patient group, such as SARS-CoV-2 convalescent [20] or immunocompromised patients [21]. The interim analysis of this study is available as a preprint on the medrxiv server [22].…”

“…Viruses 2022, 14, 1257 3 of 22 To address above-mentioned issues, we prospectively assessed the BNT162b2 vaccineelicited immune responses within healthy SARS-CoV-2-naive healthcare workers in Belgium for up to 10 months in a real-world setting with multiple VoCs emerging.…”