Differences in Responses of Immunosuppressed Kidney Transplant Patients to Moderna mRNA-1273 versus Pfizer-BioNTech

免疫抑制肾移植患者对 Moderna mRNA-1273 与辉瑞-BioNTech 的反应差异

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作者:Dulat Bekbolsynov, Andrew Waack, Camryn Buskey, Shalmali Bhadkamkar, Keegan Rengel, Winnifer Petersen, Mary Lee Brown, Tanaya Sparkle, Dinkar Kaw, Fayeq Jeelani Syed, Saurabh Chattopadhyay, Ritu Chakravarti, Sadik Khuder, Beata Mierzejewska, Michael Rees, Stanislaw Stepkowski

Abstract

Immunosuppressed kidney transplant (KT) recipients produce a weaker response to COVID-19 vaccination than immunocompetent individuals. We tested antiviral IgG response in 99 KT recipients and 66 healthy volunteers who were vaccinated with mRNA-1273 Moderna or BNT162b2 Pfizer-BioNTech vaccines. A subgroup of participants had their peripheral blood leukocytes (PBLs) evaluated for the frequency of T helper 1 (Th1) cells producing IL-2, IFN-γ and/or TNF-α, and IL-10-producing T-regulatory 1 (Tr) cells. Among KT recipients, 45.8% had anti-SARS-CoV-2 IgG compared to 74.1% of healthy volunteers (p = 0.009); also, anti-viral IgG levels were lower in recipients than in volunteers (p = 0.001). In terms of non-responders (≤2000 U/mL IgG), Moderna's group had 10.8% and Pfizer-BioNTech's group had 34.3% of non-responders at 6 months (p = 0.023); similarly, 15.7% and 31.3% were non-responders in Moderna and Pfizer-BioNTech groups at 12 months, respectively (p = 0.067). There were no non-responders among controls. Healthy volunteers had higher Th1 levels than KT recipients, while Moderna produced a higher Th1 response than Pfizer-BioNTech. In contrast, the Pfizer-BioNTech vaccine induced a higher Tr1 response than the Moderna vaccine (p < 0.05); overall, IgG levels correlated with Th1(fTTNF-α)/Tr1(fTIL-10) ratios. We propose that the higher number of non-responders in the Pfizer-BioNTech group than the Moderna group was caused by a more potent activity of regulatory Tr1 cells in KT recipients vaccinated with the Pfizer-BioNTech vaccine.

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