Immune persistence induced by two-dose BBIBP-CorV vaccine with different intervals, and immunogenicity and safety of a homologous booster dose in high-risk occupational population.

BACKGROUND: The immune persistence of neutralizing antibodies elicited by BBIBP-CorV vaccines on day 0-14, 0-21 and 0-28 schedule, and the immunogenicity and safety of a homologous booster dose after different priming vaccination regimens is scarcely reported. METHODS: : Responders (GMT≥16) at day 28, after priming with the two-dose vaccine, were followed up at 3, 6, and 10 months. Eligible participants received a homologous booster dose at month 10 and were followed-up 28 days post-booster. RESULTS: The GMT of neutralizing antibodies in 0-28d-10 m and 0-21d-10 m group were significantly higher than 0-14d-10 m group from month 3 (71.6 & 64.2 vs 46.4, p < 0.001) to month 10 (32.4 & 28.8 vs 20.3, p < 0.001) after the second dose. On day 28 post-booster, a remarkable rebound in neutralizing antibodies (246.2, 277.5, and 288.6, respectively) was observed in the three groups. All adverse reactions were mild after booster injection. CONCLUSIONS: The priming two-dose BBIBP-CorV vaccine with 0-28 days and 0-21 days schedule could lead to a longer persistence of neutralizing antibody than the 0-14 days schedule. Regardless of the priming vaccination regimens, a homologous booster dose led to a strong rebound in neutralizing antibodies and might persist for at least 18 months.

Factors associated with neutralizing antibody levels induced by two inactivated COVID-19 vaccines for 12 months after primary series vaccination.

Background: BBIBP-CorV and CoronaVac inactivated COVID-19 vaccines are widely-used, World Health Organization-emergency-listed vaccines. Understanding antibody level changes over time after vaccination is important for booster dose policies. We evaluated neutralizing antibody (nAb) titers and associated factors for the first 12 months after primary-series vaccination with BBIBP-CorV and CoronaVac. Methods: Our study consisted of a set of cross-sectional sero-surveys in Zhejiang and Shanxi provinces, China. In 2021, we enrolled 1,527 consenting 18-59-year-olds who received two doses of BBIBP-CorV or CoronaVac 1, 3, 6, 9, or 12 months earlier and obtained blood samples and demographic and medical data. We obtained 6-month convalescent sera from 62 individuals in Hebei province. Serum nAb titers were measured by standard micro-neutralization cytopathic effect assay in Vero cells with ancestral 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 analyzed nAb titer trends using Chi-square and factors related to nAb titers with logistic regression and linear models. Results: Numbers of subjects in each of the five month-groupings ranged from 100 to 200 for each vaccine and met group-specific target sample sizes. Seropositivity rates from BBIBP-CorV were 98.0% at 1 month and 53.5% at 12 months, and GMTs were 25.0 and 4.0. Respective seropositivity rates from CoronaVac were 90.0% and 62.5%, and GMTs were 20.2 and 4.1. One-, three-, six-, nine-, and twelve-month GMCs were 217.2, 84.1, 85.7, 44.6, and 10.9 IU/mL in BBIBP-CorV recipients and 195.7, 94.6, 51.7, 27.6, and 13.4 IU/mL in CoronaVac recipients. Six-month convalescent seropositivity was 95.2%; GMC was 108.9 IU/mL. Seropositivity and GMCs were associated with age, sex, and time since vaccination. Conclusions: Neutralizing Ab levels against ancestral SARS-CoV-2 from BBIBP-CorV or CoronaVac vaccination were similar and decreased with increasing time since vaccination; over half of 12-month post-vaccination subjects were seropositive. Seropositivity and GMCs from BBIBP-CorV and CoronaVac six and nine months after vaccination were similar to or slightly lower than in six-month convalescent sera. These real-world data suggest necessity of six-month booster doses.

Safety and immunogenicity of inactivated SARS-CoV-2 vaccine in high-risk occupational population: a randomized, parallel, controlled clinical trial.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (COVID-19) have a substantial burden on health-care systems around the world. This is a randomized parallel controlled trial for assessment of the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, aiming to determine an appropriate vaccination interval of the vaccine for high-risk occupational population. METHODS: In an ongoing randomized, parallel, controlled phase IV trial between January and May 2021 in Taiyuan City, Shanxi Province, China, we randomly assigned the airport ground staff and public security officers aged 18 to 59 years to receive two doses of inactivated SARS-CoV-2 vaccine at 14 days, 21 days, or 28 days. The serum neutralizing antibody to live SARS-CoV-2 was performed at baseline and 28 days after immunization. Long-term data are being collected. The primary immunogenicity endpoints were neutralization antibody seroconversion and geometric mean titer (GMT) at 28 days after the second dose. Analysis of variance (ANOVA), chi-square, and logistic regression analysis were used for data analysis. RESULTS: A total of 809 participants underwent randomization and received two doses of injections: 270, 270, 269 in the 0-14, 0-21, and 0-28 vaccination group, respectively. By day 28 after the second injection, SARS-CoV-2 neutralizing antibody of GMT was 98.4 (95% CI: 88.4-108.4) in the 0-14 group, which was significantly lower compared with 134.4 (95% CI: 123.1-145.7) in the 0-21 group (P < 0.001 vs 0-14 group) and 145.5 (95% CI: 131.3-159.6) in the 0-28 group (P < 0.001 vs 0-14 group), resulting in the seroconversion rates to neutralizing antibodies (GMT ≥ 16) of 100.0% for all three groups, respectively. The intention-to-treat (ITT) analysis yielded similar results. All reported adverse reactions were mild. CONCLUSIONS: Both a two-dose of inactivated SARS-CoV-2 vaccine at 0-21 days and 0-28 days regimens significantly improved SARS-CoV-2 neutralizing antibody level compared to the 0-14 days regimen in high-risk occupational population, with seroconversion rates of 100.0%. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100041705, ChiCTR2100041706. Registered 1 January 2021, www.chictr.org.cn .