key: cord-0733985-wp3dczmv authors: Fonseca, Marcela Helena Gambim; de Souza, Tamiris de Fátima Goebel; de Carvalho Araújo, Fernanda Montenegro; de Andrade, Luiz Odorico Monteiro title: Dynamics of antibody response to CoronaVac vaccine date: 2022-01-28 journal: J Med Virol DOI: 10.1002/jmv.27604 sha: 6bc900d0c898b9af39b133988a16d0521e5eb402 doc_id: 733985 cord_uid: wp3dczmv CoronaVac was the first vaccine approved in Brazil for use in healthcare workers (HCWs). However, there is limited information about it, with little long‐term evidence on post‐vaccination antibody persistence. This study evaluated the antibody response to SARS‐CoV‐2 in 1237 HCWs after the first (1D), second dose (2D), and 6 months postvaccination (6mA2D) with CoronaVac. The seropositivity was 88% at 1D, increasing to 99.8% at 2D, but decreasing to 97.9% at 6mA2D, which was also observed at the analyzed antibody levels. Interestingly, the levels in females were higher than males, and we found a positive correlation with previous SARS‐CoV‐2 infection. Participants with comorbidities had lower levels suggesting the need to monitor for a potential booster dose. Our findings suggest that CoronaVac induced a robust antibody response that wanes significantly over time. Further longitudinal studies are needed to identify whether the antibodies will decline or plateau at a lower level. The SARS-CoV-2 coronavirus pandemic has been an unprecedented level of global collaboration that has led to a rapid development of vaccines. Various candidate vaccines are being developed and tested, including nucleic acid vaccines, inactivated virus vaccines, live attenuated vaccines, protein or peptide subunit vaccines, and viral-vectored vaccines. [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] In Brazil, the CoronaVac was approved for emergency use and vaccination started on January 2021, in health care workers (HCWs). HCWs were prioritized in the vaccination programs because they are directly exposed to infected patients and can receive a high viral load. 14, 15 CoronaVac was developed by Chinese biopharmaceutical company Sinovac Life Sciences and uses the inactivated whole SARS-CoV-2 virus. In the vaccination schedule using a CoronaVac, a second dose of vaccine should occur 2-4 weeks after the first dose. 16 The early protective efficacy of a vaccine is primarily conferred by the induction of antigen-specific antibodies. Long-term protection requires the persistence of vaccine antibodies above protective thresholds and/or the maintenance of immune memory cells capable of reactivation after subsequent viral exposure. 17 A rapid decay of anti-SARS-CoV-2 antibodies in convalescent COVID-19 patients has been reported, raising the question of whether COVID-19 vaccines will elicit long-lasting immune protection. [18] [19] [20] [21] [22] [23] With the continued potential for more transmissible SARS-CoV-2 variants, data on antibody dynamics of vaccine-induced immune responses are essential to understand the protection and durability of vaccine and clarify the need for further booster doses. Limited information is available about CoronaVac, with little long-term evidence on the postvaccination antibody persistence. Therefore, this 2 | METHODS The study was approved by the Ethics Committee of the Hospital Geral Dr. César Cals, through CAAE 39691420.7.0000.5049. For the purpose of this study, 1237 HCWs of both genders, aged 18 years and above, that have received two doses of the vaccine CoronaVac between February to April 2021 were included after an informed consent. An additional evaluation was performed between July and September 2021, after 6 months they received the second dose, when 805 HCWs that were included on the previous phases remained. HCWs who did not take the vaccine or who were unable to collect blood samples within the period determined by the study were excluded. This study involved 29 institutions that provide health care services in Ceará State, Brazil. Twenty-five institutions are components of public Brazilian health system and 4 are private organizations. Services that provide primary care until reference hospitals of high-complexity procedures were included in the study. All participants answered a questionnaire with information on demographic and clinical data. The history of COVID-19 was considered before the first dose administration or after the second dose. HCWs who had COVID-19 between the first and second dose of CoronaVac were excluded of the study. Therefore, The HCWs with COVID-19 history, included in the study, received the same CoronaVac schedule than HCWs who did not have COVID-19. The second dose were administered 28 days after the first dose in all participants. Sequential serum samples were collected from HCWs at three different times: 28 days after the first vaccine dose (1D), 30 days (2D) and 6 months after the second dose of CoronaVac (6mA2D). The participants' blood was collected at the workplace. The samples were sent to the Serology Laboratory of the COVID-19 Diagnosis Support Unit of Fundação Oswaldo Cruz, Ceará, Brazil, for serological analysis. All samples were tested for immunoglobulin G (IgG) anti-SARS-CoV-2 using the SARS-CoV-2 IgG II Quant Assay (Abbott). The chemiluminescent immunoassay measures antibodies against the receptor-binding domain (RBD) of the S1-subunit of the SARS-CoV-2 S protein and presents 100% positive agreement with the plaque reduction neutralization test. This antibody test has a sensitivity and specificity of 99.4% and 99.6%, respectively. 24 All steps of the assay were realized according to the manufacturer´s instructions. The chemiluminescence signal was detected by the ARCHITECT i2000SR equipment (Abbott). The analyzer calculates antibody concentration in arbitrary concentration units (AU/ml). Results ≥50 AU/ml (cutoff value) are reported as positive and results <50 AU/ml are reported as negative. The cohort consisted of 1237 HCWs that received two doses of the Although all HCWs completed their allocated two-dose vaccination schedule, serum samples were obtained from 805 professionals after 6 months following the second dose, 638 females (79.3%) and 167 (20.7%) males. The antibody response was studied at three time points (Table 2 ). In Antibody levels were compared between the age groups, but no statistically significant difference was found ( Figure 2B ). In 1D, the In this study, 239 (19%) participants informed that they have co- Although, the long-term evidence on the postvaccination antibody persistence in older populations remains to be studied. After the vaccination, previously infected participants had a significantly higher antibody levels than previously uninfected participants. Post-vaccination antibody levels positively correlated with previous infection were described by other studies. 29, [34] [35] [36] [37] Interestingly, an increase of antibodies in previously infected participants was not observed after the second dose of vaccine. HCWs with a history of COVID-19 seems to reach a peak of antibodies already in the first dose, so that a second dose does not increase the response. This phenomenon can be explained by the fact that in a conventional multidose vaccine schedule, the first dose generates a primary immune response, and the second dose generates the boosted anamnestic response. In patients who had COVID-19, their prior infections will serve as a priming dose of antigen; the first vaccination dose then, in effect, becomes the booster shot. 38 Additionally, several studies make note that the second dose in this situation provides virtually no additional boost to antibody levels. 29 This study has limitations since we the seroprevalence of SARS-CoV-2 antibodies in HCWs before vaccination was not evaluated. Therefore, the seroconversion rate was not defined. In addition, no specific risk group such as individuals with age over 70 years was included. Furthermore, the male population was underrepresented, hence conclusions on gender differences in vaccine response need further studies. Finally, the neutralizing activity of antibodies and T cell responses were not assessed. Taken together, the study reports a robust evidence of antibody response to CoronaVac after two doses, which were declined at 6 months postvaccination. Further longitudinal studies are needed to identify whether the antibodies will continue to decline or plateau at a lower level and determine what level is protective, clarifying the necessity of booster doses. We thank the 1237 volunteers and the 29 health care institutions for participating in this study. We also thank the researcher Dr. Paulo Goberlânio de Barros Silva for the statistical analysis. The project is funded by Fundação Oswaldo Cruz and Ministério da Saúde, Brazil. The authors declare no conflict of interest. Data are available on request due to privacy or ethical restrictions. The data that support the findings of this study are available from the corresponding author. 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