Ηumoral and cellular SARS-CoV-2 immunity in renal transplant recipients following BNT162b2 mRNA vaccination
Asimina Fylaktou1, Efstratios Kasimatis2, Aliki Xochelli1, Anastasia Papadopoulou3, Vasiliki Nikolaidou1, Erasmia Sampani2, Despoina Asouchidou1, Maria Stangou2, Evangelia Yannaki3, Georgios Tsoulfas4, Aikaterini Papagianni2.
1National Peripheral Histocompatibility Center, Immunology Department, Hippokration General Hospital, Thessaloniki, Greece; 2Department of Nephrology, Aristotle University Medical School, Hippokration General Hospital, Thessaloniki, Greece; 3Hematology Department-Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center, George Papanikolaou Hospital, Thessaloniki, Greece; 4Division of Organ Transplantation, Department of Surgery, Aristotle University Medical School, Hippokration General Hospital, Thessaloniki, Greece
Introduction: Kidney transplant recipients show poor humoral immune response following SARS-CoV-2 vaccination. Knowledge of vaccine-induced cellular immunity and its association with antibody titers is limited.
Method: SARS-CoV-2–specific neutralizing antibodies (Nab) were measured with chemiluminescence immunoassay in 53 naive kidney transplant recipients after the 2nd dose and before and after the 3rd dose of BNT162b2 mRNA vaccination. Nab were also measured in 23 Covid-19-recovered renal transplant patients before vaccination. Anti-HLA Abs were detected using Luminex to estimate any increase in HLA sensitization after vaccination. In 39 vaccinated patients with no Nab detected after the 2nd dose, SARS-CoV-2–specific T cells response was studied using interferon (IFN)-γ ELISpot analysis before and one month after the 3rd dose.
Results: One month after the 2nd dose, only 15% of the naive patients demonstrated positive Nab and only 10% preserved them four months later. After the 3rd dose responders increased to 70%, and Nab was preserved in a repeat measurement four months later. Antibody titers after the 3rd dose, had a median value of 9.6 times above the cut-off value; however, they decreased to six times (p=0.003) four months later. Regarding anti-HLA Abs, neither MFI nor HLA specificities increased after vaccination, and none of the patients developed dnDSAs. Of the Covid-19-recovered transplant recipients, 74% demonstrated positive Nab with a median value three times above the cut-off value. In a repeat measurement before vaccination (median time 5 months later), 55% of recovered patients retained their Nab. SARS-CoV-2–specific T cells response was demonstrated in 41% of patients with nonresponse after the 2nd dose. The 3rd dose improved cellular immunity in these transplant recipients, as a specific T cell response was demonstrated in 64% of patients, with a significant increase (p=0.001) in specific T lymphocyte titers.
Conclusion: Vaccination against SARS-CoV-2 appears to be safe regarding the development of anti-HLA Abs in kidney transplant recipients. The humoral immune response improved after the 3rd dose in naive patients, with Nab induced alike to Covid-19-recovered patients, although antibody titers declined four months later. Cellular immunity was present in many patients with primary humoral nonresponse before the 3rd dose and further improved after the 3rd dose, in parallel with Nab induction.
