Material and methods
In this study, we present the 6-month humoral and cellular results from the participants of the multicenter and prospective CRO-VAX HCP study who received the bivalent booster (ethical approval number: 2020‐006149‐21; Appendix ). Thirty-six were females (median age = 51.0 years; IQR = 43.0–58.8) and 15 were males (median age = 51.0 years; IQR = 35.0–59.0). Ages were non-significantly different between females and males (p = 0.88). The majority of the participants (45/51; 88.2%) had a history of SARS-CoV-2 (Appendix ).
A pseudovirus‐neutralization test was used to assess the neutralization potency of vaccines‐elicited antibodies against either the D614G strain, the delta variant, the BA.5 omicron variant, or the XBB.1.5 omicron subvariant. The antibody titer is determined as the dilution of serum at which 50% of the infectivity is inhibited (IC50) as determined by a nonlinear sigmoid regression model. A sample with a titer of less than 1:20 is considered negative (Appendix ). Neutralizing antibodies against BA.5 were measured at each timepoint but neutralizing antibodies against the D614G strain, the delta variant and the XBB.1.5 omicron subvariant were only measured at 6 months in a subset of 30 participants randomly selected.
Total antibodies against the NCP (Roche Diagnostics) were measured using the Elecsys Anti‐SARS‐CoV‐2 assay. Results above 0.165 cut‐off index were considered positive (Appendix ).
The T cell-mediated immune response was assessed using the cobas IGRA SARS-COV-2 Tubes and the Elecsys IGRA SARS‑CoV‑2 assay (Roche Diagnostics). The test measures the release of interferon gamma (IFNγ) from T cells in response to an in vitro SARS-CoV-2 stimulation in whole blood samples which have been formerly in contact with the SARS-CoV-2 coated antigens. More than 180 different SARS-CoV-2 antigens (structural (spike, membrane and nucleocapsid) and non-structural) are coated on the antigen tube, enabling a substantial coverage of commonly occurring HLA subtypes for stimulation of both CD4+ and CD8+ T cells. The assay is therefore robust to detect different variants. A result above 0.013 IU/mL was considered positive (Appendix ).
The detailed statistical analysis process is presented in theAppendix .