The vaccine named CoronaVac which is applied in our country and evaluated the antibody responses after vaccination in our study is a vaccine containing aluminium hydroxide adjuvant produced by Sinovac company in China. The Phase I/II study was conducted in a single-centre, double-blinded, randomized placebo-controlled study in China with 743 individuals aged between 18–59, and the vaccine was found to be effective and safe as a result of a study (19). 144 individuals participated in the Phase I study of this vaccine, and 3-µg and 6 µg doses of vaccine were administered on two different schemes for 0–14 days and 0–28 days. In the study, antibody levels were between 46–50% in the blood samples obtained on the 14th day, while it was 83% in the 3- µg group and 79% in the 6-µg group on the 28th day. Phase II study was conducted with 600 individuals in May 2020 and antibody responses were 92% for 3 µg, 98% for 6 µg in the 0-14-day scheme; it was found to 97% and 100% in the 0-28th day scheme, respectively.
In the Phase III study of the same vaccine conducted in Brazil, individuals both aged 18–59 and > 60 years old were included (20). In the Phase III study in Brazil, 600 SU (3 µg) vaccine was used and the 0-14-day scheme was applied. 2270 (36.6%) male, 3925 (63.4%) female healthcare workers with a mean age of 39.42 participated in the study. The age distribution was recorded as 5879 individuals aged between 18–59 (94.9%), 316 individuals aged between > 60 (5.10%). The results of the Brazilian study were announced on January 7, 2021, and it was emphasized that the "clinical efficacy" level was reported as 78% and the "general efficacy" level as 50.4%, while the rate of protection from mild illness was 78% and the rate of protection from severe illness was 100%. About the low rate of effectiveness in this study, it has been explained as the high number of cases in the period when the study was conducted in Brazil and the detection of a large number of Covid patients in both the placebo and the study group. In addition, it was reported that the participants in the study were healthcare workers who were at a much higher risk for COVID-19, many parameters were accepted as positive, and even if they were not evaluated in other vaccine studies. For these reasons, it was estimated that its efficacy may have been relatively low (21–23).
CORONAVAC Phase III study conducted in Turkey has started on September 14 2020 and 24 centres participated. As of December 23 2020, 918 healthcare workers and 6453 individuals from the public (total 7371 people) were included, and the efficacy rate of the vaccine administered at a dose of 3 µg with a 0-14-day scheme was reported as 91.25% (24).
There are other inactivated vaccine studies in China and different countries, and new studies are still ongoing (25, 26).
As it can be seen, while the efficacy of the vaccine was reported to be decent in Phase I-II studies regarding the vaccine named Coronavac which we evaluated in our study, different rates of responses were observed in other countries where phase III studies were conducted. In our study, when the response rate against the vaccine was evaluated, the weak response rate was 9.5% and the decent response rate was 82.2%. One of the reasons for the different rates could be that the vaccine was administered with the 0–14 days scheme in some Phase III studies, and the 0–28 days scheme was used in this study. In addition, it was thought that this situation may have been observed due to different test kits and different measurement methods.
In our study, we found that the antibody response was weakened with advancing age, and this difference increased more significantly over the age of 60. Although higher rates were reported in the Phase studies conducted by Wu et al. in individuals over 60 years old, this difference could be occurring due to the fact that our analysis was performed with the ELISA method and Wu's study was performed with the PRNT method, and our number of people over 60 years old was lower. However, we still think that more realistic data can be obtained, and the issue of age should be considered by following up the larger number of vaccinated individuals over the age of 60. The concept of immune aging is rather complex and there is no validated method for measuring its degree. With advancing age, the numerical value of T cells capable of responding to a vaccine and the survival rate of T cells, especially CD8 T cells, decreases significantly. B cells, on the other hand, although their number does not decrease much with age, less functional antibodies are produced due to the decreased expression of certain proteins. Therefore, lower antibody responses can be expected in the elderly (27, 28).
In our study, it was also found that being male was associated with low antibody response. As it is known, there is evidence that the immunological response to antigen may differ between genders. In women, the number and activity of innate immune cells such as monocytes, macrophages, and dendritic cells are higher than in men. Thus, responses to both infections and vaccines can be higher in women compared to men. Women have a higher proportion of CD4 + T cells and CD4 +/CD8 + T cells rate; CD8 + T cell count is also lower than men. B cell count, IgG and IgM are similar in adulthood in both genders. Adult women typically have a high inflammatory cell-mediated immune response to vaccines which may explain the better effectiveness of vaccines in women than in men (29–31).
There was no emphasis on gender in any of the Phase studies conducted on CoronaVac, and we think that the higher vaccine response in women identified in our study should be considered when monitoring larger cohorts.
As an interesting data, it was determined that 54 of the healthcare professionals participating in our study had pandemic vaccine during the H1N1 pandemic in 2009, and antibody unresponsiveness developed against COVID-19 vaccine was found to be slightly higher in these individuals (p: 0.024). Although the number is fewer, we think that this issue should be evaluated in more detail in other studies. Again, in our study, it was determined that antibody unresponsiveness was higher in people who did not have PVAE, meaning that PVAE was slightly higher in those with high antibody response (p: 0.011). This situation may be elucidated by the lower rate of development or sense of PVAE in those with lower immune responses.
In our study, those who had COVID-19 and, then, the vaccine had higher antibody titres in accordance with our expectations. Certain studies demonstrated that the antibody response in people is reduced after the COVID-19 infection, especially in those who are asymptomatic. In a study about SARS, it was reported that the antibodies developed decreased over time, and this decrease accelerated after the 16th month and even disappeared in the third year (32, 33). It is difficult to predict how long the antibodies will continue to be presented in those who have the disease, and whether there will be a difference in the duration of antibody persistence in those vaccinated after the disease, and it is not clear for now. We anticipate that this issue will be clarified with long-term follow-up.
As with many infectious diseases that can be prevented by vaccination, it seems important to vaccinate a significant part of the community with available and accessible vaccines, as well as protective measures such as hand washing, mask-distance to protect from COVID-19 infection. Since inactivated vaccines are developed with conventional methods and do not carry live virus particles, they are considered safer. However, individuals vaccinated with inactivated vaccines should also be monitored in terms of Antibody-dependent enhancement (ADE) and Vaccine-associated enhanced respiratory disease (VAERD) as in other COVID-19 vaccines (34, 35). Additionally, it is not yet clear whether the formation of strong antibodies against the inactivated vaccine will protect people from COVID-19 infection or how long this protection will continue. Moreover, it should be kept in mind that the antibody levels measured in serum against the vaccine only show the B lymphocyte response, the T cell activity representing the memory cells is also very important in the response to the vaccine, and the sensitivity of these tests will be lower than the neutralization test results with PRNT.
This study had some limitations, primarily that we did not have the information about the previous vaccination antibody levels. The previous antibody levels would have srtrengthen our results. The sample size is limited therefore the size increase may affect mean results.
Strength of the study is that all our sample consists of the health professionals therefore all COVID-19 PCR records and COVID-19 medical records were well known. Thus, the finding of our study is stronger.