Booster Dose of SARS-CoV-2 mRNA Vaccine in Kidney Transplanted Patients Induces Wuhan-Hu-1 Specific Neutralizing Antibodies and T Cell Activation but Lower Response against Omicron Variant

Abstract

Kidney transplanted recipients (KTR) are at high risk of severe SARS-CoV-2 infection due to immunosuppressive therapy. Although several studies reported antibody production in KTR after vaccination, data related to immunity to the Omicron (B.1.1.529) variant are sparse. Herein, we analyzed anti-SARS-CoV-2 immune response in seven KTR and eight healthy controls after the second and third dose of the mRNA vaccine (BNT162b2). A significant increase in neutralizing antibody (nAb) titers were detected against pseudoviruses expressing the Wuhan-Hu-1 spike (S) protein after the third dose in both groups, although nAbs in KTR were lower than controls. nAbs against pseudoviruses expressing the Omicron S protein were low in both groups, with no increase after the 3rd dose in KTR. Reactivity of CD4+ T cells after boosting was observed when cells were challenged with Wuhan-Hu-1 S peptides, while Omicron S peptides were less effective in both groups. IFN-γ production was detected in KTR in response to ancestral S peptides, confirming antigen-specific T cell activation. Our study demonstrates that the 3rd mRNA dose induces T cell response against Wuhan-Hu-1 spike peptides in KTR, and an increment in the humoral immunity. Instead, humoral and cellular immunity to Omicron variant immunogenic peptides were low in both KTR and healthy vaccinated subjects.

Neutralizing antibody responses and cellular responses against SARS-CoV-2 Omicron subvariants after mRNA SARS-CoV-2 vaccination in kidney transplant recipients

“…KTXRs are at a risk of severe SARS-CoV-2 infection because of their reduced T-cell immunity 43 . A previous study indicated that the third mRNA dose induced a T cell response against WT spike peptides in KTXRs, while cellular immunity toward Omicron BA.1 variant immunogenic peptides was low in both KTXRs and healthy controls 9 . However, no studies have evaluated the T-cell responses to Omicron BA.5 spike peptides.…”

“…KTXRs have more severe SARS-CoV-2 infection than healthy controls 3 – 7 . Furthermore, KTXRs have lower neutralizing antibody titers and cellular responses against B.1.1 (WT), B.1.617.2 (Delta), and B.1.1.529 (Omicron BA.1) after SARS-CoV-2 vaccination than healthy controls 8 , 9 . However, to our knowledge, few studies have evaluated neutralizing antibodies and cellular responses against Omicron BA.5 in KTXRs.…”

Five doses of the mRNA vaccination potentially suppress ancestral-strain stimulated SARS-CoV2-specific cellular immunity: a cohort study from the Fukushima vaccination community survey, Japan

“…However, considering the potential for immune tolerance and exhaustion in cellular immunity after repeated mRNA vaccine administration (especially five or more doses), there might be an alternative strategy for SARS-CoV-2 immunization. The potential evasion of cellular immune responses to VoCs following the emergence of the Omicron variant ( 30 ) further emphasizes the need to re-evaluate vaccination strategies for high-risk groups. Thus, a booster with the monovalent vaccine targeting the latest VoC may be beneficial to avoid the suppression of cellular immune response observed in the part of our patients.…”

Neutralizing antibody responses and cellular responses against SARS-CoV-2 Omicron subvariant BA.5 after mRNA SARS-CoV-2 vaccination in kidney transplant recipients

“…KTXRs have more severe SARS-CoV-2 infection than healthy controls [3][4][5][6][7] . Furthermore, KTXRs have lower neutralizing antibody titers and cellular responses against B.1.1 (WT), B.1.617.2 (Delta), and B.1.1.529 (Omicron BA.1) after SARS-CoV-2 vaccination than healthy controls [8][9][10] .…”