SARS-CoV-2 specific antibody responses after third CoronaVac or BNT162b2 vaccine following two-dose CoronaVac vaccine regimen

COVID-19 vaccination campaign in Turkey started with two-dose regimen of CoronaVac (Sinovac Life Sciences), a chemically inactivated whole virus vaccine (IVV), in January 2021.1 It has been reported that humoral immune response to SARS-CoV-2 variants, such as 501Y.V2 (B.1.351), of the plasma and neutralizing antibodies elicited by CoronaVac suggest that a third-dose boost may be beneficial for combating SARS-CoV-2 variants when necessary.2 Recent rapid spread of the Delta variant worldwide, and the fact that this variant has partially nullified vaccination3 against SARS-CoV-2 forced many countries to consider application of additional vaccine doses. While administering third dose of messenger RNA (mRNA) vaccine was recommended for recipients in solid organ transplants in France4, 5 in April 2021, Turkish Ministry of Health recommended application of the third vaccine dose for healthcare workers (HCWs) and elderly people by the end of June 2021. By September 2021, more than 9 M Turkish citizens already had their third dose of CoronaVac or BNT162b2 vaccine.6 Some other countries (the United Arab Emirates, Thailand, Indonesia) also started giving a third shot to those inoculated with IVV. On the other hand, people in Israel were twice vaccinated with BNT162b2, and a third dose of the same type of mRNA vaccine was distributed to citizens over 60 years old.7 In this study, we compared the antibody recognizing the receptor binding domain of the spike (S), glycoprotein (IgG-S), and nucleocapsid protein (IgG-N) of SARS CoV-2 titers to investigate the interplay between humoral immune responses in 68 HCWs. CoronaVac was applied to 1030 HCWs of Yeditepe University Hospitals in two-dose regimens. Randomly selected 45 HCWs who had no previous infection were enrolled in this study (2IVV group). We compared the antibody recognizing the RBD of the spike (S) glycoprotein (IgG-S) and nucleocapsid protein (IgG-N) of SARS CoV-2 titers to investigate the interplay between humoral immune responses of HCWs. First antibody titers in 2IVV group were measured 1 month after administering second CoronaVac (booster1) dose. Grouping of HCWs was done after third (booster2) dose application (timing, in Figure 1). Second antibody titers were measured 1 month after third (=booster2) dose. 3IVV group contained 18 healthy HCWs of mean (SD) age of 41 (10.9) years, who had a third CoronaVac (booster2) dose approximately 6 months after the application of their prime dose. 2IVV + BNT group of 27 HCWs with mean age 40.7 (11.1) years had BNT162b2 vaccine as the third vaccine (booster2) dose approximately 6 months after the application of their first CoronaVac. Healthy control group (HCG) consisted of 23 “nonvaccinated and noninfected” HCWs with mean age 31 (6.4) years. Peripheral blood samples were collected for serology from all 68 participants who provided written informed consent for use of their blood samples. The presence of IgG-S and IgG-N antibody levels against SARS-CoV-2 were measured quantitatively by using Abbott Architect i2000 (Abbott Laboratories). Age structures of all groups were normally distributed and did not significantly differ from each other (independent t test, p > 0.05). However, IgG-S and IgG-N sample values for the 3IVV and 2IVV + BNT groups were not normally distributed. Measured IgG-S levels for 3IVV and 2IVV + BNT groups as well as IgG-N titers for both groups showed statistically significant differences (Mann–Whitney UIgG-S = 0, p < 0.001; Mann–Whitney UIgG-N = 84, p < 0.001). Measured IgG-S and IgG-N titers in the 3IVV group presented a high Spearman's correlation value (ρ = 0.715, p < 0.001), but correlation coefficient between IgG-S and IgG-N titers in 2IVV + BNT group was negligible (ρ = 0.063, p > 0.05). Table 1 lists descriptive statistics in the study groups. Median values of IgG-S titers were substantially higher in 2IVV + BNT group than those HCWs of the 3IVV and HCG. On the other hand, median values of IgG-N titers were higher in 3IVV group than those HCWs of the other two groups. While third CoronaVac inoculations yield 1.7 and 1.8 times increases in median values of IgG-S and IgG-N titers, respectively; BNT162b2 administration as the third vaccine dose boosted IgG-S median titers by a factor of 46.6, but IgG-N titers decreased by a factor of 6.5. Two-dimensional visualization of humoral responses using threshold values of each variable are displayed in Figure 1. More populated first quadrant with the same color of dot-scattering in this graph is the indicator of response effectivity in each study group against related SARS-CoV-2 immunity parameters. By clinically following the HCWs participated in our study, we will be able to tell which of these two vaccination programs provide higher protection against SARS-CoV-2. Limitations of this study are the absence of cellular immunity assays and relatively small sample size. We express our gratitude to all healthcare workers of Yeditepe University Hospitals who participated in this study. We are also thankful to anonymous reviewers for their constructive comments and suggestions. Aynur Eren Topkaya conceived the work and contributed to the design of the study. Ali Umit Keskin, Sibel Bolukcu, Aynur Eren Topkaya, Pinar Ciragil performed the literature search, Ali Umit Keskin, Aynur Eren Topkaya, and Pinar Ciragil contributed to the writing of the manuscript. Aynur Eren Topkaya supervised the project. Aynur Eren Topkaya, Sibel Bolukcu, and Pinar Ciragil were responsible for the recruitment, follow-up, and data collection, and laboratory analysis. Ali Umit Keskin performed data processing work. All authors contributed to the data interpretation, revision of the manuscript and approved the final manuscript version. All study data were available to all authors.