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