Results
The highest measured neutralizing capacity against the BA.5 variant was
reached at day 28 with a GMT of 1,095 (95% CI = 903.4–1,327),
representing a significant 7.0‐fold increase from baseline (i.e., 157;
95% CI = 112–219, p < 0.0001). A substantial decrease was
then observed up to 180 days with an observed GMT of 47.4 (95% CI =
36.6–61.6, p < 0.0001), which represents a 23.1‐fold
decrease. The neutralizing capacity at 180 days was significantly lower
compared to baseline (p = 0.0004). The proportion of detectable
neutralizing antibodies (i.e., <1:20) was 93.6%, 100%,
100%, 98.0%, and 85.4% at baseline and 14, 28, 90, and 180 days after
the administration of the vaccine (Figure 1A ). The fold-change
in the neutralizing capacity against BA.5 was similar between
participants who received the BA.1 or the BA.4/5 booster (p
> 0.05) (Appendix ). The estimated
T1/2 of neutralizing antibodies was 16.1 days (95% CI =
10.2–38.4 days). According to the model, a mean time of 137 days (95%
CI = 76–170) would be needed to cross the dilution titer threshold of
1:20 (Figure 1B ).
At 6 months, neutralizing antibodies against the Delta variant, the BA.5
omicron variant and the XBB.1.5 omicron subvariant were 1.97, 5.20, and
10.81 lower compared to the D614G strain. The proportion of detectable
neutralizing antibodies was 100%, 100%, 91.3%, and 66.6%,
respectively (Figure 1C ).
The highest T-cell response was observed after 14 days with a GMT of
0.95 UI/mL (95% CI = 0.72–1.24), representing a significant 1.97‐fold
increase from baseline (i.e., 0.48; 95% CI = 0.30–0.77, p = 0.0306). A
significant decrease was then observed up to 180 days with an observed
GMT of 0.41 (95% CI = 0.21–0.82, p = 0.0083), representing a 2.28‐fold
reduction compared to day 14 and a 1.17-fold decrease from baseline. The
IFNγ responses at 90 and 180 days were not different from baseline (p =
0.91 and 0.95). The proportion of detectable levels of IFNγ was 98%,
100%, 100%, 100%, and 95% at baseline, 14, 28, 90, and 180 days
(Figure 1D ). The fold-change in the IFNγ response against BA.5
was similar between participants who received the BA.1 or the BA.4/5
booster (Appendix ).
Eleven participants (21.6%) developed a breakthrough infection between
90 and 180 days; which is consistent with the drop of neutralizing
antibodies. The infection was associated with a significant raise in
BA.5 neutralizing antibodies (fold-increase of 2.55, p = 0.0039). The
impact on the IFNγ release was not significant in these patients (p =
0.4961) (Appendix ).