A Third Dose of an Inactivated Vaccine Dramatically Increased the Levels and Decay Times of Anti-SARS-CoV-2 Antibodies, but Disappointingly Declined Again: A Prospective, Longitudinal, Cohort Study at 18 Serial Time Points Over 368 Days

Abstract

BackgroundDue to anti-SARS-CoV-2 antibody decay and SARS-CoV-2 variants, vaccine booster doses are a constant concern. It was focused on whether the third dose can quickly evoke and activate immunity and produce a sufficient and durable immune protection.ObjectivesTo evaluate the responses and durations of five subsets of anti-SARS-CoV-2 antibodies and their predictive values for protection after the administration of a three-dose inactivated SARS-CoV-2 vaccines regimens.MethodsA prospective cohort study of five subsets of anti-SARS-CoV-2 antibodies (neutralizing antibody, anti-RBD total antibody, anti-Spike IgG, anti-Spike IgM, and anti-Spike IgA) was carried out to evaluate the efficacies and immune characteristics of a three-dose inactivated SARS-CoV-2 vaccines regimen in 32 volunteers. The dynamic response and immune decay were longitudinally profiled at 18 serial time points over 368 days.ResultsThe neutralizing antibody, anti-RBD total antibody, anti-Spike IgG and anti-Spike IgA levels rapidly increased to 773.60 (380.90-1273.00) IU/mL, 639.30 (399.60-878.60) AU/mL, 34.48 (16.83-44.68) S/CO and 0.91 (0.35-1.14) S/CO, respectively, after the administration of the third dose. Compared to the peak value after the second dose, these values were increased by 4.22-fold, 3.71-fold, 1.01-fold and 0.92-fold. On the other hand, the half-lives of the neutralizing antibody, anti-RBD total antibody, and anti-Spike IgG were 56.26 (95% CI, 46.81 to 70.49) days, 66.37 (95% CI, 54.90 to 83.88) days, and 82.91 (95% CI, 63.65 to 118.89) days, respectively. Compared to the half-lives after the second dose, these values were increased by 1.71-fold, 2.00-fold, and 2.93-fold, respectively. Nevertheless, the positive conversion rate of anti-Spike IgM was decreased to 9.38% (3/32), which was much lower than that after the second dose (65.63% (21/32)).ConclusionsCompared to the second dose, the third dose dramatically increased the antibody levels and decay times. However, the half-life of neutralizing antibody remained unsatisfactory. Due to decay, a fourth dose, and even annual revaccination, might be considered in the SARS-CoV-2 vaccination management strategy.

Is the fourth COVID-19 vaccine dose urgently needed? Revelation from a prospective cohort study

“…First, the neutralizing antibody, anti-RBD total antibody, and anti-Spike IgG levels declined over time, with half-lives of 81.14 days, 105.66 days, and 104.76 days within 180 days after the third dose, respectively, as esti-mated by an exponential decay model, which increased 2-4 fold compared with those after the second dose 5 and were longer than those within 3 months after the third dose in our previous study. 4 The power law model estimated half-lives for the neutralizing antibody of 293.88 days, anti-RBD total antibody of 468.98 days, and anti-Spike IgG of 467.28 days, which were longer than those estimated by the exponential decay model ( Fig. 2 A-C), indicating that the concentration of these antibodies may be starting to stabilize.…”

“…A prospective cohort study design was employed as we previously reported. 4 41 participants received the three-dose Coron-aVac vaccine ( Fig. 1 A) and provided blood donation at 8 serial time points within 180 days after the third dose.…”

Developing new COVID-19 vaccine against the variants is urgently needed rather than boosters: A longitudinal cohort study

“…The 32 participants were the same as those who participated in a previous study ( 4 ). They gave blood samples at 20 serial time points during the course of three doses of CoronaVac vaccine within 552 days ( Figure 1 A).…”

“…A robust correlation was reported between neutralizing antibody titer and COVID-19 vaccine efficacy ( 6 ). The neutralizing antibody concentration showed a small response after the first dose, peaking at 207.40 IU/mL 2 weeks after the second dose (42 days) and then declining as relatively fast to 4.75 IU/mL (≥54.00 IU/mL considered as positive ( 4 )) at 276 days (about 9 months) during the primary immunization. After the third dose, the level rapidly increased and peaked at 711.90 IU/mL at 2 weeks and then began to very slowly decline, remaining at 115.23 IU/mL at 276 days (about 9 months) during the secondary immunization ( Figure 1 B), which was significantly higher than that of 9 months after the primary immunization ( p < 0.001).…”

Antibody Persistence and Safety through 6 Months after Heterologous Orally Aerosolised Ad5-nCoV in individuals primed with two-dose CoronaVac previously

“…The immunogenicity of using homologous or heterologous vaccine as the third dose in adults who had received with two-dose CoronaVac at 3 months after the booster dose have been previously reported [12][13][14][15]. Compared to these studies, we presented data for longer follow-up period.…”