Study of efficacy and antibody duration to fourth-dose booster of Ad5-nCoV or inactivated SARS-CoV-2 vaccine in Chinese adults: a prospective cohort study.

Introduction: China experienced a record surge of coronavirus disease 2019 cases in December 2022, during the pandemic. Methods: We conducted a randomized, parallel-controlled prospective cohort study to evaluate efficacy and antibody duration after a fourth-dose booster with Ad5-nCoV or inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Results: A total of 191 participants aged ≥18 years who had completed a three-dose regimen of the inactivated SARS-CoV-2 vaccine 6 months earlier were recruited to receive the intramuscular Ad5-nCoV booster or the inactivated SARS-CoV-2 vaccine. The Ad5-nCoV group had significantly higher antibody levels compared with the inactivated vaccine group at 6 months after the fourth vaccination dose. After the pandemic, the breakthrough infection rate for the Ad5-nCoV and the inactivated vaccine groups was 77.89% and 78.13%, respectively. Survival curve analysis (p = 0.872) and multivariable logistic regression analysis (p = 0.956) showed no statistically significant differences in breakthrough infection between the two groups. Discussion: Compared with a homologous fourth dose, a heterologous fourth dose of Ad5-nCoV elicited a higher immunogenic response in healthy adults who had been immunized with three doses of inactivated vaccine. Nevertheless, the efficacy of the two vaccine types was equivalent after the pandemic.

Safety and immunogenicity of Ad5-nCoV immunization after three-dose priming with inactivated SARS-CoV-2 vaccine in Chinese adults.

Data on the safety and immunity of a heterologous booster (fourth dose) after three-doses of inactivated SARS-CoV-2 vaccine in Chinese adults are limited. We evaluate the safety and immunogenicity of Ad5-nCoV in a randomized, double-blind, parallel-controlled phase 4 clinical trial in Zhejiang, China (NCT05373030). Participants aged 18-80 years (100 per group), administered three doses of inactivated SARS-CoV-2 vaccine ≥6 months earlier, are enrolled and randomized 1:1 into two groups, which are administered intramuscular Ad5-nCoV or inactivated SARS-CoV-2 vaccine (CoronaVac or Covilo). All observed adverse reactions are predictable and manageable. Ad5-nCoV elicits significantly higher RBD-specific IgG levels, with a geometric mean concentration of 2924.0 on day 14 post-booster, 7.8-fold that of the inactivated vaccine. Pseudovirus-neutralizing antibodies to Omicron BA.4/5 show a similar pattern, with geometric mean titers of 228.9 in Ad5-nCoV group and 65.5 in inactivated vaccine group. Ad5-nCoV booster maintains high antibody levels on day 90, with seroconversion of 71.4%, while that of inactivated vaccine is 5.2%, almost pre-booster levels. A fourth Ad5-nCoV vaccination following three-doses of inactivated SARS-CoV-2 vaccine is immunogenic, tolerable, and more efficient than inactivated SARS-CoV-2 vaccine. Ad5-nCoV elicits a stronger humoral response against Omicron BA.4/5 and maintains antibody levels for longer than homologous boosting.

Evaluation of antibody kinetics and durability in healthy individuals vaccinated with inactivated COVID-19 vaccine (CoronaVac): A cross-sectional and cohort study in Zhejiang, China.

Background: Although inactivated COVID-19 vaccines are proven to be safe and effective in the general population, the dynamic response and duration of antibodies after vaccination in the real world should be further assessed. Methods: We enrolled 1067 volunteers who had been vaccinated with one or two doses of CoronaVac in Zhejiang Province, China. Another 90 healthy adults without previous vaccinations were recruited and vaccinated with three doses of CoronaVac, 28 days and 6 months apart. Serum samples were collected from multiple timepoints and analyzed for specific IgM/IgG and neutralizing antibodies (NAbs) for immunogenicity evaluation. Antibody responses to the Delta and Omicron variants were measured by pseudovirus-based neutralization tests. Results: Our results revealed that binding antibody IgM peaked 14-28 days after one dose of CoronaVac, while IgG and NAbs peaked approximately 1 month after the second dose then declined slightly over time. Antibody responses had waned by month 6 after vaccination and became undetectable in the majority of individuals at 12 months. Levels of NAbs to live SARS-CoV-2 were correlated with anti-SARS-CoV-2 IgG and NAbs to pseudovirus, but not IgM. Homologous booster around 6 months after primary vaccination activated anamnestic immunity and raised NAbs 25.5-fold. The neutralized fraction subsequently rose to 36.0% for Delta (p=0.03) and 4.3% for Omicron (p=0.004), and the response rate for Omicron rose from 7.9% (7/89)-17.8% (16/90). Conclusions: Two doses of CoronaVac vaccine resulted in limited protection over a short duration. The inactivated vaccine booster can reverse the decrease of antibody levels to prime strain, but it does not elicit potent neutralization against Omicron; therefore, the optimization of booster procedures is vital. Funding: Key Research and Development Program of Zhejiang Province; Key Program of Health Commission of Zhejiang Province/ Science Foundation of National Health Commission; Major Program of Zhejiang Municipal Natural Science Foundation; Explorer Program of Zhejiang Municipal Natural Science Foundation.

Immunogenicity and immune-persistence of the CoronaVac or Covilo inactivated COVID-19 Vaccine: a 6-month population-based cohort study.

Background: Owing to the coronavirus disease 2019 (COVID-19) pandemic and the emergency use of different types of COVID-19 vaccines, there is an urgent need to consider the effectiveness and persistence of different COVID-19 vaccines. Methods: We investigated the immunogenicity of CoronaVac and Covilo, two inactivated vaccines against COVID-19 that each contain inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The levels of neutralizing antibodies to live SARS-CoV-2 and the inhibition rates of neutralizing antibodies to pseudovirus, as well as the immunoglobulin (Ig)G and IgM responses towards the spike (S) and nucleocapsid (N) protein of SARS-CoV-2 at 180 days after two-dose vaccination were detected. Results: The CoronaVac and Covilo vaccines induced similar antibody responses. Regarding neutralizing antibodies to live SARS-CoV-2, 77.9% of the CoronaVac vaccine recipients and 78.3% of the Covilo vaccine recipients (aged 18-59 years) seroconverted by 28 days after the second vaccine dose. Regarding SARS-CoV-2-specific antibodies, 97.1% of the CoronaVac vaccine recipients and 95.7% of the Covilo vaccine recipients seroconverted by 28 days after the second vaccine dose. The inhibition rates of neutralizing antibody against a pseudovirus of the SARS-CoV-2 Delta variant were significantly lower compared with those against a pseudovirus of wildtype SARS-CoV-2. Associated with participant characteristics and antibody levels, persons in the older age group and with basic disease, especially a chronic respiratory disease, tended to have lower anti-SARS-CoV-2 antibody seroconversion rates. Conclusion: Antibodies that were elicited by these two inactivated COVID-19 vaccines appeared to wane following their peak after the second vaccine dose, but they persisted at detectable levels through 6 months after the second vaccine dose, and the effectiveness of these antibodies against the Delta variant of SARS-CoV-2 was lower than their effectiveness against wildtype SARS-CoV-2, which suggests that attention must be paid to the protective effectiveness, and its persistence, of COVID-19 vaccines on SARS-CoV-2 variants.

Detection of serum antibody levels after inoculation of an inactivated SARS-CoV-2 vaccine / 预防医学

Objective @#To investigate the serum levels of antibodies against SARS-CoV-2 after inoculation of an inactivated SARS-CoV-2 vaccine, so as to provide insights into the evaluation of the vaccine immunogenicity. @*Methods @#In this single-arm Objective performance criteria trial, residents aged 18 to 59 years and inoculated with an inactivated SARS-CoV-2 vaccine in Xihu District, Hangzhou City from October to December of 2020 were selected using a cluster sampling method. Blood samples were collected prior to inoculation, 14 and 28 days post-inoculation of the first dose, and 28 days post-inoculation of the second dose. Serum levels of anti-SARS-CoV-2 IgM and IgG antibodies were detected using the magnetic particle-based chemiluminescence immunoassay. The seroconversion of antibodies and dynamic changes of antibody levels were analyzed.@*Results @#Totally 310 participants were enrolled, including 133 subjects on day 14 post-inoculation of the first dose, 97 subjects on day 28 post-inoculation of the first dose and 254 subjects on day 28 post-inoculation of the second dose. The seroconversion rates of anti-SARS-CoV-2 IgG antibody were 6.02%, 28.87% and 98.43%, and the median IgG antibody levels were 1.76 ( interquartile range, 3.25 ), 5.69 ( 9.95 ) and 52.05 ( 47.60 ) AU/mL ( P<0.05 ), respectively, while the seroconversion rates of anti-SARS-CoV-2 IgM antibody were 9.02%, 11.34% and 12.99%, and the median IgG antibody levels were 1.89 ( 3.28 ), 2.06 ( 4.71 ) and 2.65 ( 4.01 ) AU/mL ( P>0.05 ), respectively. In addition, higher serum levels of anti-SARS-CoV-2 IgG and IgM antibodies were detected post-inoculation relative to pre-inoculation ( P<0.05 ), and higher serum IgG antibody levels were found in subjects aged 18 to 39 years than in those aged 40 to 59 years ( P<0.05 ). @*Conclusions @#Inoculation of two doses of the inactivated SARS-CoV-2 vaccine achieves a high immunogenicity among residents aged 18 to 59 years 28 days post-inoculation, and the anti-SARS-CoV-2 IgM antibody is detectable in some residents following inoculation of the first dose.