Fig. 2. SARS-CoV-2-specific immune responses before and after
bivalent booster vaccination. (A-C) Blood was collected from 18
HCWs 11 (IQR 5-31) days before (T1) and 57 (IQR 38-65) days after (T2)
bivalent booster vaccination with 70 (IQR 69-71) days in between the two
timepoints. (D-F) Immune responses of 8 HCWs who received no
bivalent booster vaccination were also assessed at similar time points
with an interval of 70 (IQR 69.5-75.5) days. (A,D) Spike
S1-specific T cell responses. (B,E) Anti-RBD (ancestral) IgG
concentrations. (C,F) Omicron BA.5 serum neutralization
activity. HCWs were excluded if a previous (booster) vaccination was
received within three months before T1 or if the HCW tested SARS-CoV-2
RT-qPCR positive in between T1 and T2. Data are represented as median
with IQR and were assessed by a Wilcoxon signed-rank test.
Ratio of Omicron BA.5 to ancestral SARS-CoV-2 strain-specific
immunological responses after Omicron BA.5 infection and
ancestral/Omicron BA.1 bivalent vaccination
We determined the effect of a recent Omicron BA.5 infection, an
ancestral/Omicron BA.1 bivalent booster vaccination, and both on Omicron
BA.5 and ancestral SARS-CoV-2 specific immunity. For this purpose, we
stimulated PBMCs with solely Omicron BA.5 mutation peptides and the
corresponding ancestral strain spike peptides. Also, we performed sVNT
assays using either Omicron BA.5 or ancestral SARS-CoV-2 pseudovirus
particles.
At T1, the T cell responses against these specific peptides were overall
low, and the Omicron BA.5/ancestral ratios were comparable between the
two groups (Fig. 3A and Supplementary Fig. 2A) . The
neutralization activity was not significantly different between the two
groups at T1 (Figure 3B) . However, 92% of recently infected
HCWs versus 57% of non-recently infected HCWs exhibited higher (i.e., a
ratio of >1) neutralization activity against Omicron BA.5
compared to the ancestral strain.
At T2, T cell responses were also overall low and only the HCWs who were
both recently infected with Omicron BA.5 and received a bivalent booster
vaccination had 2.2-fold higher T cell responses against Omicron BA.5
than against ancestral strain (Figure 3C and Supplementary Fig.
2C) . Strikingly, this HCW group also demonstrated a 2.4-fold higher
neutralizing activity against Omicron BA.5 compared to ancestral strain,
which was higher (p = 0.0456) than in HCWs who received a bivalent
vaccination but without a recent Omicron BA.5 infection (Fig.
3D) . The latter group exhibited a 1.4-fold higher neutralization
activity.
For comparison, we also assessed the Omicron BA.5/ancestral
neutralization ratios in pre-Omicron BA.5 serum samples which were
obtained before and after monovalent booster vaccination in
2021.12 Accordingly, we observed that there was an
overall higher neutralizing activity of the ancestral strain than of
BA.5 (Supplementary Fig. 2) .