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.