Immunogenicity and Adverse Effects of the 2‐Dose BNT162b2 Messenger RNA Vaccine Among Liver Transplantation Recipients

Abstract

The BNT162b2 messenger RNA (mRNA) vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to be safe and effective in immunocompetent patients. The safety and efficacy of this vaccine in liver transplantation (LT) recipients is still under evaluation. The objective of this study was to assess the safety and efficacy of the BNT162b2 vaccine among transplant recipients. The immune responses of 76 LT recipients receiving 2 doses of the vaccine were compared with those of 174 age-matched immunocompetent controls. Postvaccination immunoglobulin G (IgG) antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 and neutralizing antibodies (NA) to the BNT162b2 mRNA vaccine were determined at least 14 days after the second dose of the vaccine. IgG antibody titers ≥1.1 were defined as positive antibodies. Adverse effects were monitored during the study period. Following administration of the second dose, transplant recipients showed reduced immune responses compared with controls (72% versus 94.2%; P < 0.001). At a median time of 38 days after the second vaccination, the geometric mean of RBD IgG and NA titers were 2.1 (95% confidence interval [CI], 1.6-2.6) and 150 (95% CI, 96-234) among transplant recipients and 4.6 (95% CI, 4.1-5.1) and 429 (95% CI, 350-528) in the control group, respectively (P < 0.001). Antibody responses were lower in transplant recipients who were receiving combined immunosuppression therapy and in those with impaired renal function. Among the LT recipients with negative antibody responses, 1 became infected with SARS-CoV-2, but no recipients with positive antibody responses became infected. Overall, most (n = 39 [51%]) adverse effects self-reported by transplant recipients were mild and occurred more often in women than in men. Compared with patients who were immunocompetent, LT recipients had lower immune responses. The durability of immune responses to the BNT162b2 vaccine among LT recipients requires further investigation.

A third dose of the BNT162b2 mRNA vaccine significantly improves immune responses among liver transplant recipients

“…Adverse effects (mostly mild) were reported by 50% of the patients after the second dose of BNT162b2 mRNA vaccine 10 . Following the third dose, adverse effects were mild and reported by 37% of patients.…”

“…The reduced immune response was observed more in patients who received combined immunosuppression treatments (combination of calcineurin inhibitor (CNI) with mycophenolate mofetil (MMF), or sirolimus, or everolimus, and/or low-dose steroids) and patients with renal impairment 4 , 5 , 6 , 7 . We have reported a 72% positive immune response rate among 76 LT recipients after the second dose of the BNT162b2 mRNA vaccine 10 . Kamar et al reported improved immune response after the third BNT162b2 mRNA dose, administered to SOT recipients (78 kidney-transplant recipients, 12 LT recipients, eight lung-trans- plant or heart-transplant recipients, and three pancreas transplant recipients) 61 days after the second dose 11 .…”

“…Levels of anti-RBD IgG and NA were available for 47 of 61 patients who had participated in our previous study 10 , which evaluated the humoral immune response of LT patients to two doses of the BNT162b2 mRNA vaccine. We compared the humoral immune response separately among the 47 patients at three-time points: after the second vaccine (median 38 days (IQR, 21-52) after the second dose), immediately before the third vaccine, and after the third vaccine (median 22 days (IQR, 21-28) after the third dose).…”

“…The BNT162b2 mRNA vaccine against SARS-CoV-2 has been shown to be safe and effective in immunocompetent subjects , 1 , 2 , 3 . In contrast, solid organ transplant (SOT) recipients were reported to have impaired immune responses after two doses of the vaccine 4 , 5 , 6 , 7 , 8 , with liver transplant (LT) recipients showing a better immune response to the mRNA vaccine than other SOT recipients 4 , 9 , 10 . The reduced immune response was observed more in patients who received combined immunosuppression treatments (combination of calcineurin inhibitor (CNI) with mycophenolate mofetil (MMF), or sirolimus, or everolimus, and/or low-dose steroids) and patients with renal impairment 4 , 5 , 6 , 7 .…”

Gastroenterology 2022: Groundhog Day

“…2 However, we have observed suboptimal vaccine responses in some of our gastroenterology patient cohorts. Patients with inflammatory bowel disease (IBD) treated with infliximab were demonstrated to have attenuated antibody responses, 3 as did patients post liver transplantation 4 and those with chronic liver disease. 5 Subsequently, the British Society of Gastroenterology (BSG) has recommended and advocated for booster dosing in these cohorts.…”