Humoral immunity in dually vaccinated SARS-CoV-2-naïve individuals and in booster-vaccinated COVID-19-convalescent subjects

Abstract

Background The immune response to COVID-19-vaccination differs between naïve vaccinees and those who were previously infected with SARS-CoV-2. Longitudinal quantitative and qualitative serological differences in these two distinct immunological subgroups in response to vaccination are currently not well studied. Methods We investigate a cohort of SARS-CoV-2-naïve and COVID-19-convalescent individuals immediately after vaccination and 6 months later. We use different enzyme-linked immunosorbent assay (ELISA) variants and a surrogate virus neutralization test (sVNT) to measure IgG serum titers, IgA serum reactivity, IgG serum avidity and neutralization capacity by ACE2 receptor competition. Results Anti-receptor-binding domain (RBD) antibody titers decline over time in dually vaccinated COVID-19 naïves whereas titers in single dose vaccinated COVID-19 convalescents are higher and more durable. Similarly, antibody avidity is considerably higher among boosted COVID-19 convalescent subjects as compared to dually vaccinated COVID-19-naïve subjects. Furthermore, sera from boosted convalescents inhibited the binding of spike-protein to ACE2 more efficiently than sera from dually vaccinated COVID-19-naïve subjects. Conclusions Long-term humoral immunity differs substantially between dually vaccinated SARS-CoV-2-naïve and COVID-19-convalescent individuals. Booster vaccination after COVID-19 induces a more durable humoral immune response in terms of magnitude and quality as compared to two-dose vaccination in a SARS-CoV-2-naïve background.

An Integrative Analysis of the Immune Features of Inactivated SARS-CoV-2 Vaccine (CoronaVac)

“…A balance seemed to exist between cellular and humoral immune responses, which dominated at early and late stages of vaccination, respectively. The high serum-neutralizing antibody titers and distinct PBMC transcriptomics of the Month 8 recovery control contrasted to unvaccinated healthy participants, implying that human immunity to SARS-CoV-2 could sustain at least eight months, which supported long-term resistance to SARS-CoV-2, which is consistent with previous studies [36]. While scRNA-seq demonstrated increased B cell levels and altered PBMC transcriptomics from Day 0 to 14 after the first vaccination, the serum-neutralizing antibody titers from Day 14 and 28 were not significantly higher than those before vaccination, implying that scRNAseq was more sensitive than antibody titer assays.…”

Kinetics of the SARS-CoV-2 Antibody Avidity Response Following Infection and Vaccination

“…We could observe the same rapid boost in antibody avidity 10 weeks after vaccination in individuals who were previously infected, up to the maximal value of 100%. Other studies have reported a similar net increase in antibody avidity in previously exposed individuals receiving a vaccine booster dose, which was associated with a more efficient binding inhibition of spike to ACE2 in an in vitro competition assay [ 33 ]. It would be interesting to investigate whether this steeper increase in avidity associated with vaccination is caused by an acceleration of affinity maturation in germinal centers or simply reflects an ongoing trajectory towards a more complete process of affinity maturation.…”

Quantitative Analysis of Anti-N and Anti-S Antibody Titers of SARS-CoV-2 Infection after the Third Dose of COVID-19 Vaccination

“…Moreover, at 6 months after the third dose of the BNT162b2 vaccine, the level of anti-S antibodies in individuals with a negative SARS-CoV-2 infection history was reported as 379–2960 AU/mL [ 18 ]. Humoral immunity, represented by the neutralization capacity via the ACE2 receptor competition, has also been reported to decrease starting at 6 months after the booster vaccination [ 19 ]. In this study, similar to previous studies, a comparison of anti-S antibodies at 1 and 4 months after the third vaccination revealed that anti-S antibodies had decreased at 4 months compared to 1 month.…”