3.1 SARS-CoV-2 antibody features in 2-year convalescents after inactivated vaccines
To increase the vaccination rate coverage of SARS-CoV-2 and construct herd immunity, the 2-year COVID-19 convalescents in Macheng were vaccinated in the second half of 2021. Herein, to assess SARS-CoV-2-specific antibody features of COVID-19 convalescents, who had recovered for 2 years after inactivated vaccines (CoronaVac or BBIBP-CorV or WIBP-CorV), sera from participants was evaluated for the presence of IgG, IgM, IgA, and NAb together with the vaccinated healthy control donors in the same town (Figure 1A). We found that over 96% of 2-year convalescents after inactivated vaccines have a positive IgG response to WT, as presented by the double positive for ELISA and MCLIA tests (Supplementary Table 1). No significant difference was observed in the positive proportion of IgG between the healthy individuals (ELISA: 85.7%, MCLIA: 94.3%) and 2-year convalescents (96.1% for both methods) after the inoculation of inactivated vaccines (Supplementary Table 1). However, IgG levels of 2-year convalescents after inactivated vaccines were higher compared to healthy individuals with either vaccinated (p < 0.0001) or unvaccinated (p < 0.0001, Figure 1B, C). 2-year convalescents after vaccination exhibited IgG titers that were 1.2-fold more than healthy individuals after vaccination (Figure 1B, C). Certain levels of IgM could be detected in both vaccinated 2-year convalescents and healthy individuals but with no significant difference (31.4% vs 28.6% in ELISA; 23.5% vs 20.0% in MCLIA) (Figure 2A, B and Supplementary Table 1).
To reveal the dynamic antibody responses within the convalescents, we retrieved the paired sera at the 6-month and 1-year follow-up visits of the convalescents. The 2-year convalescents had higher IgG antibodies following vaccination in contrast with the 1-year visit, with 50% (9/18) of employees increased more than 1-fold (p = 0.005 for ELISA and p = 0.004 for MCLIA), but with no difference with the 6-month visit (Figure 1D, E). However, a significant reducing trend was observed for IgM levels among the convalescents from 6 months to 2-year recovery, although the convalescents were vaccinated before the 2-year visit (Figure 2C, D). We next analyzed whether severity affected the levels of IgG/IgM, and no differences were observed among vaccinated 2-year convalescents with different disease severities (Figure 1F, G and Figure 2E, F).
We also tested the IgA antibody within the sera of the donors. 58.8% (30/51) of 2-year convalescents had positive IgA responses to SARS-CoV-2 S protein RBD, which were significantly higher compared with the vaccinated individuals without prior infection (Figure 1H). For a longitudinal analysis of the IgA antibodies among the convalescents, the avidity of IgA antibodies decreased from 6-month to 1-year visits but increased significantly during the 2-year visit in the convalescents (Figure 1I).
To demonstrate the potential influence of the vaccination dose on the antibody levels among the convalescents and the healthy individuals, we compared the antibodies from healthy individuals after 3 doses and 2-year convalescents vaccinated with 2 doses. The IgG, IgA, and NAb levels of 2-year convalescents after 2 doses of inactivated vaccines were even higher than healthy individuals with 3 doses of vaccination (Supplementary Figure 1A, B, E, F). No IgM differences were observed between the two groups (Supplementary Figure 1C, D). Overall, these results suggest that 2-year convalescents after inoculated inactivated vaccines possibly develop and maintain stronger IgG, IgA, and NAb but not IgM antibodies responses to the WT stain than vaccinated healthy individuals.