Expectedly, we were unable to show an association between anti-RBD-antibody avidity and titers, suggesting that the kinetics of B cell maturation, plasma cell expansion and antibody production are different. Similarly, sera from boosted convalescents inhibited spike-protein to ACE2 receptor binding more effectively than TMA-DPH sera from dually vaccinated COVID-19 na?ves, and this activity persisted better over time in boosted convalescents than in dually vaccinated COVID-19 na?ves. more durable. Similarly, antibody avidity is considerably higher TMA-DPH among boosted COVID-19 convalescent subjects as compared to dually vaccinated COVID-19-na?ve subjects. Furthermore, sera from boosted convalescents inhibited the binding of spike-protein to ACE2 more efficiently than sera from dually vaccinated COVID-19-na?ve subjects. Conclusions Long-term humoral immunity differs substantially between dually vaccinated SARS-CoV-2-na? ve 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-na?ve background. Supplementary Information The online version contains supplementary material available at 10.1007/s15010-022-01817-8. Keywords: COVID-19, SARS-CoV-2, Antibody-mediated immunity, SARS-CoV-2-vaccination, Avidity, Surrogate neutralization Introduction We are currently experiencing yet another wave of the SARS-CoV-2 pandemic worldwide, with rapidly increasing numbers of cases in many countries, caused mainly by non-vaccinated individuals despite broad vaccination campaigns [1C3]. However, it has become evident that also fully (dually) vaccinated individuals can get infected by SARS-CoV-2 and become symptomatically ill, albeit rarely with a severe course of disease [1, 4]. It appears that immunity to SARS-CoV-2 wanes over time after both SARS-CoV-2 infection and dual vaccination, so that earlier expectations that dual vaccination would provide long-term protective immunity to COVID-19 have not been met [5]. The underlying mechanisms for what appears to be a relatively rapid decay of protective immunity to SARS-CoV-2 are as yet unclear. We previously described the natural TMA-DPH course of antibody levels directed against the SARS-CoV-2 receptor-binding domain as well as SARS-CoV-2 reactive interferon- producing T cells over a 1-year period in a cohort of 136 hospital employees who developed COVID-19 during the first wave of SARS-CoV-2 TMA-DPH infections Rabbit Polyclonal to JunD (phospho-Ser255) between March and May 2020 [6, 7]. We also reported the effects of a single dose booster vaccination with the various licensed COVID-19 vaccines on antibody levels in COVID-19 convalescents TMA-DPH and in 30 healthy, COVID-19 na?ve individuals after dual vaccination [7]. In this follow-up investigation, we describe the further course of antibody titers over a 6-month period after vaccination in the same cohorts and characterize the vaccine-induced humoral immunity in depth by quantification of the serum avidity and ACE2 competitive neutralization capacity. Methods Study cohort and blood sampling The cohort of this study has been described in detail previously [6, 7]. In brief, employees of the Kliniken Sdostbayern Hospital Network (Bavaria, Germany) who recovered from a RT-PCR-confirmed COVID-19 episode between April and June 2020 were asked to participate in the prospective cohort study. After written informed consent, participants were asked to provide samples (collected in S-Monovette syringes, Sarstedt, Nmbrecht, Germany) during various time points after recovery. When vaccines against COVID-19 had been approved by heath officials and became available for general use, those of the participants who agreed to receive a booster vaccination (according to the recommendations of the German vaccination advisory board (STIKO [8]) were asked to provide serum samples immediately prior to vaccination, and approximately 14?days and 6?months thereafter. Healthy employees of the Kliniken Sdostbayern and the University Hospital Regensburg without evidence of prior COVID-19 according to symptoms, negative anti-SARS-CoV-2 antibodies and repeated consistently negative SARS-CoV-2 PCR-tests served as controls and underwent the standard two-dose vaccine schedule between February and April 2021 in accordance with STIKO recommendations. They were asked to provide a serum sample immediately prior to the second vaccination, a second sample at least 14?days thereafter and a third sample after approximately 6?months. To exclude the possibility of asymptomatic breakthrough-infection, the absence of antibodies specific for SARS-CoV-2s nucleoprotein (N) in the serum sample taken 6?month after complete vaccination was furthermore analyzed using Roches Elecsys N-Test (data not shown). As a prerequisite of such analysis, the Elecsys N-Test has been reported to be highly specific and sensitive [9]. Serum was obtained from the blood samples by centrifugation within 6?h after drawing the blood and stored at???20?C until analysis. The study was approved by the University of Regensburg ethic committee (reference number 20-1896-101). Detection of SARS?CoV?2 nucleoprotein?specific antibodies Elecsys Anti-SARS-CoV-2?N-Test (Roche Diagnostics GmbH, Penzberg, Germany) was performed on a COBAS pro e 801 module according to the manufacturers recommendations and cutoff values were chosen.
