Impact of vaccination on kinetics of neutralizing antibodies against SARS-CoV-2 by Serum live neutralization test based on a prospective cohort.

How much the vaccine contributes to the induction and development of neutralizing antibodies (NAbs) of breakthrough cases relative to those unvaccinated-infected cases is not fully understood. We conducted a prospective cohort study and collected serum samples from 576 individuals who were diagnosed with SARS-CoV-2 Delta strain infection, including 245 breakthrough cases and 331 unvaccinated-infected cases. NAbs were analyzed by live virus microneutralization test and transformation of NAb titer. NAbs titers against SARS-CoV-2 ancestral and Delta variant in breakthrough cases were 7.8-fold and 4.0-fold higher than in unvaccinated-infected cases, respectively. NAbs titers in breakthrough cases peaked at the second week after onset/infection. However, the NAbs titers in the unvaccinated-infected cases reached their highest levels during the third week. Compared to those with higher levels of NAbs, those with lower levels of NAbs had no difference in viral clearance duration time (P>0.05), did exhibit higher viral load at the beginning of infection/maximum viral load of infection. NAb levels were statistically higher in the moderate cases than in the mild cases (P<0.0001). Notably, in breakthrough cases, NAb levels were highest longer than 4 months after vaccination (Delta strain: 53118.2 U/mL), and lowest in breakthrough cases shorter than 1 month (Delta strain: 7551.2 U/mL). Cross-neutralization against the ancestral strain and the current circulating isolate (Omicron BA.5) was significantly lower than against the Delta variant in both breakthrough cases and unvaccinated-infected cases. Our study demonstrated that vaccination could induce immune responses more rapidly and greater which could be effective in controlling SARS-CoV-2.

Kinetics of SARS-CoV-2 neutralizing antibodies in Omicron breakthrough cases with inactivated vaccination: Role in inferring the history and duration of infection.

Background: The quantitative level and kinetics of neutralizing antibodies (NAbs) in individuals with Omicron breakthrough infections may differ from those of vaccinated individuals without infection. Therefore, we aimed to evaluate the difference in NAb levels to distinguish the breakthrough cases from the post-immunized population to identify early infected person in an outbreak epidemic when nasal and/or pharyngeal swab nucleic acid real-time PCR results were negative. Methods: We collected 1077 serum samples from 877 individuals, including 189 with Omicron BA.2 breakthrough infection and 688 post-immunized participants. NAb titers were detected using the surrogate virus neutralization test, and were log(2)-transformed to normalize prior to analysis using Student's unpaired t-tests. Geometric mean titers (GMT) were calculated with 95% confidence intervals (CI). Linear regression models were used to identify factors associated with NAb levels. We further conducted ROC curve analysis to evaluate the NAbs' ability to identify breakthrough infected individuals in the vaccinated population. Results: The breakthrough infection group had a consistently higher NAb levels than the post-immunized group according to time since the last vaccination. NAb titers in the breakthrough infection group were 6.4-fold higher than those in the post-immunized group (GMT: 40.72 AU/mL and 6.38 AU/mL, respectively; p<0.0001). In the breakthrough infection group, the NAbs in the convalescent phase were 10.9-fold higher than in the acute phase (GMT: 200.48 AU/mL and 18.46 AU/mL, respectively; p<0.0001). In addition, the time since infection, booster vaccination, and the time since last vaccination were associated with log(2)-transformed NAb levels in the breakthrough infection group. ROC curve analysis showed that ROC area was largest (0.728) when the cut-off value of log(2)-transformed NAb was 6, which indicated that NAb levels could identify breakthrough infected individuals in the vaccinated population. Conclusion: Our study demonstrates that the NAb titers of Omicron BA.2 variant breakthrough cases are higher than in the post-immunized group. The difference in NAb levels could be used to identify cases of breakthrough infection from the post-immunized population in an outbreak epidemic.

Long-Term Kinetics of SARS-CoV-2 Antibodies and Impact of Inactivated Vaccine on SARS-CoV-2 Antibodies Based on a COVID-19 Patients Cohort.

Background: Understanding the long-term kinetic characteristics of SARS-CoV-2 antibodies and the impact of inactivated vaccines on SARS-CoV-2 antibodies in convalescent patients can provide information for developing and improving vaccination strategies in such populations. Methods: In this cohort, 402 convalescent patients who tested positive for SARS-CoV-2 by RT-PCR from 1 January to 22 June 2020 in Jiangsu, China, were enrolled. The epidemiological data included demographics, symptom onset, and vaccination history. Blood samples were collected and tested for antibody levels of specific IgG, IgM, RBD-IgG, S-IgG, and neutralizing antibodies using a the commercial magnetic chemiluminescence enzyme immunoassay. Results: The median follow-up time after symptom onset was 15.6 months (IQR, 14.6 to 15.8). Of the 402 convalescent patients, 44 (13.84%) received an inactivated vaccine against COVID-19. A total of 255 (80.19%) patients were IgG-positive and 65 (20.44%) were IgM-positive. The neutralizing antibody was 83.02%. Compared with non-vaccinated individuals, the IgG antibody levels in vaccinated people were higher (P=0.007). Similarly, antibody levels for RBD-IgG, S-IgG, and neutralizing antibodies were all highly increased in vaccinated individuals (P<0.05). IgG levels were significantly higher after vaccination than before vaccination in the same population. IgG levels in those who received 'single dose and ≥14d' were similar to those with two doses (P>0.05). Similar conclusions were drawn for RBD-IgG and the neutralizing antibody. Conclusion: 15.6 months after symptom onset, the majority of participants remained positive for serum-specific IgG, RBD-IgG, S-IgG, and neutralizing antibodies. For convalescent patients, a single dose of inactivated vaccine against COVID-19 can further boost antibody titres.