Discussion
The present study addresses the knowledge gap on the immunogenicity of
mRNA and inactivated vaccine boosters after 2 doses of inactivated
CoronaVac administration. We focused on neutralizing antibody and T cell
responses after one and three months elicited by BNT162b2 (mRNA) and
CoronaVac (inactivated) vaccine boosters in fully vaccinated individuals
with CoronaVac.
We found a 3.38-fold increase in neutralizing antibody titers (GMT
78.69) one month after the BNT162b2 booster and antibody titers were
found to be maintained after three months (GMT 80). However, in the
CoronaVac group, low GMTs after 1 month and 3 months (21.44 and 28.44)
indicated the weak immunogenicity of the CoronaVac booster. For the
protection of 50% of the individuals, a neutralizing antibody titer of
1:19 for BNT162b2 and 1:30 for CoronaVac was suggested as cutoff levels
of protection 10. All BNT162b2 booster receivers had
antibody levels above the protection threshold of 1:19 after three
months, but only 40% of donors had antibody titers above the 1:30
threshold in the CoronaVac group. High neutralizing antibody levels
following 14 days after CoronaVac booster dose 11 and
decreased neutralizing antibody levels 28 days after the CoronaVac
booster was reported 12. We found low neutralizing
antibody levels at a prolonged time (1 to 3 months) after booster doses
of CoronaVac. The concern about the weak immunogenicity would be
increased by considering the reduced efficacy of vaccines against the
omicron variant 13,14.
Current vaccine trials have focused on the stimulation of the
neutralizing antibody against SARS-CoV-2, but CD4+ and CD8+ cells also
might provide protection from severe disease and support resolution of
COVID-19 15. In our cohort, the magnitude of post
BNT162b2 booster responses was higher than the CoronaVac booster. We
detected increased IFNγ and IL-2 reactivity after the BNT162b2 booster,
accompanied by an increase in CD8+CD38+CD69+T cells. The ratio of
CD4+CD38+CD69+ cells was also high in the 3rd month of the BNT162b
booster. Robust CD8 and CD4 T-cell responses to BNT162b2 were reported
in clinical studies 16. The induction of T cell
responses after CoronaVac vaccination was also reported by a study from
Hong Kong 17. T cells clones against other SARS-CoV-2
antigens like N protein can also be stimulated with inactivated vaccines18. The type of peptide pool used for activation might
affect the results of T-cell response measurements 19.
In this study, we used the S-pool, rather than other peptides of the
virus, which might lead to underestimation of the true magnitude of
T-cell responses.
The strength of our study is being a longitudinal study and having a
unique advantage of being performed in Turkey, where the primary vaccine
schedule consisted of two CoronaVac doses. The study mainly has two
limitations, one is related to the low sample size to detect the
statistical significance especially in the CoronoVac booster group,
however, the results are in parallel with reported studies that
evaluated anti-S antibody titers by ELISA in Turkey20. Some of the recruited vaccinated donors were
excluded from the study since they received 4th doses after two months.
Secondly, we could not cover the newly emerged omicron variant. This
will be done in future studies.
Our study has implications for the countries that used a two-dose
regimen of CoronaVac. The neutralizing antibody levels after three
months of the BNT162b2 booster were higher than the antibody levels
after CoronaVac. On the other hand, specific T cells might contribute to
immune protection. By considering the waning immunity, we suggest a
second booster dose with BNT162b2 for the countries that already have
BNT162b2 or CoronaVac boosters following two doses of CoronaVac.
Acknowledgments: The authors declare no conflict of interest in
relation to this work.
Author contribution: Data and sample collection: ZEK, RE, MK,
YT, SSY, KM, OE
Laboratory work: ZEK, RE, GGE, TB, ZGT, YT, FC
Data analysis: ZEK, RE, GGE, TB, OD, OE, FC
Manuscript preparation: ZEK, RE, GGE, ZGT, OE, FC