#5687 SARS-COV-2 PREEXPOSURE PROTECTS FROM IMMUNITY-FADING AFTER MRNA VACCINATION IN KIDNEY TRANSPLANT RECIPIENTS, DIALYSIS PATIENTS, AND MEDICAL PERSONNEL
Authors: Stumpf Julian , Anders Leona , Siepmann Torsten , Schwöbel Jörg , Karger Claudia , Lindner Tom H , Faulhaber-Walter Robert , Pietzonka Annegret , Langer Torsten , Escher Katja , Anding-Rost Kirsten , Seidel Harald , Hüther Jan , Pistrosch Frank , Martin Heike , Schewe Jens , Stehr Thomas , Meistring Frank , Paliege Alexander , Schneider Daniel , Bast Ingolf , Steglich Anne , Gembardt Florian , Kessel Friederike , Kröger Hannah , Arndt Patrick , Sradnick Jan , Frank Kerstin , Skrzypczyk Sarah , Anft Moritz , Klimova Anna , Mauer René , Röder Ingo , Tonn Torsten , Babel Nina , Hugo Christian 
Published: June 2023

Abstract

Background and Aims
Immunity development and fading after SARS-CoV-2mRNA vaccination differently affects high risk populations such as dialysis or renal transplant patients compared to general population. We hypothesized that COVID-19 preexposure influences not only vaccination dependent development of immunity but also protects from immunity fading depending on vaccine type and patient group.

Method
We evaluated two and nine months follow up data in our observational DIA-Vacc study exploring specific cellular (interferon-γ release assay = IGRA) or/and humoral immune responses after 2x SARS-CoV-2mRNA vaccination in 2615 participants including medical personnel (300 MP), dialysis patients (1831 DP), kidney transplant recipients (484 KTR). Study participants were separated into COVID-19 preexposure positive (n = 405) versus negative (n = 2210) groups, where symptomatic or asymptomatic COVID-19 disease before start of vaccination was confirmed by clinical symptoms, PCR positivity and/or Spike S1/core antiSARS-CoV-2 antibodies.

Results
Two months (T2) after first vaccination, seroconversion and T-cell immunity success rates for MP and DP were excellent (86-100%) and independent on COVID-preexposure. In KTR, vaccination-related seroconversion rate on T2 almost doubled with COVID-preexposure (84% versus 45% without), a result consistent with all different antibody measurements (IgA, IgG, or receptor binding domain-RBD). Nine months after first vaccination in COVID-19 negative study patients, the percentage of patients with RBD-antibody fading results &gt;50% remained low in MP (18%), high in DP (53%) and intermediate in KTR (39%). In contrast, in all patient groups with COVID-19 preexposure RBD-antibody fading reactions &gt;50% within nine months after vaccination were almost vanished (4% in MP, 8% in DP and 0% in KTR). COVID-19 preexposure in DP also reduced T-cell immunity fading as measured by IGRA, where only 9% of patients showed a &gt;50% titer decrease compared to 34% of DP without any COVID-19 preexposure. Similar results were also seen regarding vaccination dependent regulation of antiSARS-Cov-2 IgG antibodies dependent on COVID-19 preexposure. These results are also reflected by increased mean antibody titers for IgG- and RBD-antibodies nine months after vaccination in all COVID-19 preexposed compared to non-exposed groups. In addition, the degree of antibody fading after vaccination was not just dependent on COVID-19 preexposure status but also on mRNA vaccine type being used. In MP with COVID-preexposure, 22% of BNT162b2mRNA but 0% of 1273-mRNA vaccinated study participants experienced RBD-antibody fading &gt;50% within nine months after vaccination start. This significant difference was even greater in COVID-19 preexposed DP, in whom vaccination with BNT162b2mRNA caused RBD-antibody fading &gt;50% in 36% compared to 6% of 1273-mRNA treated DP. The patient number in the KTR group was not high enough for a vaccine type comparison. This vaccine dependent influence on antibody fading is consistent with our results in patient groups without COVID-19 preexposure.

Conclusion
Long term immunity time course is markedly modified via COVID-preexposure in a mRNA vaccine dependent matter. Hybrid immunity after COVID-19 preexposure almost completely lacks immunity fading between two and nine months especially in 1273-mRNA vaccinated MP, DP, or KTR. Immune monitoring shows great individual variability dependent on personal patient history and should be especially used for pandemic patient management in vulnerable groups such as DP and KTR.