Kinetics and Factors Associated With 12-Month Persistence of Neutralizing Antibody Induced by Two Inactivated COVID-19 Vaccines

Background: BBIBP-CorV (Sinopharm, Beijing CNBG) and CoronaVac (Sinovac, Co., Ltd) inactivated COVID-19 vaccines are widely-used, World Health Organization-listed vaccines for pandemic control. Understanding antibody kinetics and persistence after BBIBP-CorV and CoronaVac vaccination is essential for management of booster campaigns. We evaluated neutralizing antibody (nAb) titers and explored variables predicting nAb titers for the first 12 months after vaccination with BBIBP-CorV and CoronaVac. Methods: Our study was a cross-sectional survey in two sites, Zhejiang and Shanxi provinces, located in southern and northern China, respectively. The study was conducted in 2021 and enrolled 1,527 individuals, 18-59 years of age, who had received two doses of either BBIBP-CorV or CoronaVac. We obtained blood samples 1, 3, 6, 9, and 12 months post-vaccination. We also obtained 6-month convalescent sera from 62 individuals in Hebei province who recovered from laboratory-proven COVID-19. Demographic characteristics and presence of chronic medical conditions were assessed using a structured questionnaire. Serum nAb titers were measured by standard micro-neutralization cytopathic effect (CPE) assay in Vero cells with SARS-CoV-2 strain HB01. We used the first WHO International Standard (IS) for anti-SARS-CoV-2 immunoglobulin (NIBSC code 20/136) to standardized geometric mean concentrations (IU/ml) derived from the nAb geometric mean titers (GMT over 1:4 was considered seropositive). We assessed trends of nAb titers over time since vaccination using Chi-square and used logistic regression analyses and used a linear model to analyze factors related to nAb titers. Findings: Neutralizing seropositivity after two doses of BBIBP-CorV was 98·0% at 1 month and 53·5% at 12 months (trend X2=109·0, P<0·001); GMTs were 25·0 [95%CI: 21·3-29·4] and 4·0 [95%CI: 3·5-4·4], respectively. After two doses of CoronaVac, seropositivity was 90·0% at 1 month and 62·5% at 12 months (trend X2=56·3, P<0·001), and GMTs were 20·2 [95%CI: 16·3-24·9] and 4·1 [95%CI: 3·7-4·5]. GMCs (IU/mL) of nAb at 1, 3, 6, 9 and 12 months were 217·2 [95%CI: 178·5-264·3], 84·1 [95%CI: 68·1-103·9], 85·7 [95%CI: 69·1-106·3], 44·6 [95%CI: 36·1-55·0], and 10·9 [95%CI: 8·7-13·8] in 768 BBIBP-CorV recipients. Respective GMCs were 195·7 [95%CI: 139·5-274·5], 94·6 [95%CI: 79·8-112·1], 51·7 [95%CI: 41·3-64·9], 27·6 [95%CI: 22·5-33·9], and 13·4 [95%CI: 10·8-16·6] in 759 CoronaVac recipients. Neutralizing seropositivity and GMC for convalescent sera 6 months after COVID-19 infection were 95·2% and 108·9 [95%CI: 81·5-145·4] IU/mL, respectively. Regression analyses showed that seropositivity and GMC were associated with age, sex, and time since vaccination. Interpretation: Kinetics of nAb following vaccination with either BBIBP-CorV or CoronaVac were similar, and showed 12-month persistence of seropositivity against prototype SARS-CoV-2 virus. Neutralizing immunity induced by BBIBP-CorV and CoronaVac 6 months and 9 months after vaccination is similar to or slightly lower than convalescent sera 6 months after natural infection based on seropositivity and GMC, supporting the need for booster at the time around 6 months after the second dose.Funding Information: This work was supported by the Chinese Center for Disease Control and Prevention Research Founding (JY21-3-01) and the National Natural Science Foundation of China (Grant 82041021 and Grant 82061138008). Declaration of Interests: The authors state they have no conflicts of interest to declare.Ethics Approval Statement: The study protocol and informed consent form were approved by the Medical Ethics Committee of The Chinese Center for Disease Control and Prevention (Approval notice: 202101). Written informed consent was obtained from all study participants.