Decline in Antibody Concentration 6 Months After Two Doses of SARS-CoV-2 BNT162b2 Vaccine in Solid Organ Transplant Recipients and Healthy Controls

Abstract

BackgroundPrevious studies have indicated inferior responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination in solid organ transplant (SOT) recipients. We examined the development of anti-receptor-binding domain (RBD) immunoglobulin G (IgG) after two doses of BNT162b2b in SOT recipients 6 months after vaccination and compared to that of immunocompetent controls.MethodsWe measured anti-RBD IgG after two doses of BNT162b2 in 200 SOT recipients and 200 matched healthy controls up to 6 months after first vaccination. Anti-RBD IgG concentration and neutralizing capacity of antibodies were measured at first and second doses of BNT162b2 and 2 and 6 months after the first dose. T-cell responses were measured 6 months after the first dose.ResultsIn SOT recipients, geometric mean concentration (GMC) of anti-RBD IgG increased from first to second dose (1.14 AU/ml, 95% CI 1.08–1.24 to 11.97 AU/ml, 95% CI 7.73–18.77) and from second dose to 2 months (249.29 AU/ml, 95% CI 153.70–385.19). Six months after the first vaccine, anti-RBD IgG declined (55.85 AU/ml, 95% CI 36.95–83.33). At all time points, anti-RBD IgG was lower in SOT recipients than that in controls. Fewer SOT recipients than controls had a cellular response (13.1% vs. 59.4%, p < 0.001). Risk factors associated with humoral non-response included age [relative risk (RR) 1.23 per 10-year increase, 95% CI 1.11–1.35, p < 0.001], being within 1 year from transplantation (RR 1.55, 95% CI 1.30–1.85, p < 0.001), treatment with mycophenolate (RR 1.54, 95% CI 1.09–2.18, p = 0.015), treatment with corticosteroids (RR 1.45, 95% CI 1.10–1.90, p = 0.009), kidney transplantation (RR 1.70, 95% CI 1.25–2.30, p = 0.001), lung transplantation (RR 1.63, 95% CI 1.16–2.29, p = 0.005), and de novo non-skin cancer comorbidity (RR 1.52, 95% CI, 1.26–1.82, p < 0.001).ConclusionImmune responses to BNT162b2 are inferior in SOT recipients compared to healthy controls, and studies aiming to determine the clinical impact of inferior vaccine responses are warranted.

Incidence and severity of SARS-CoV-2 infections in liver and kidney transplant recipients in the post-vaccination era: Real-life data from Denmark

“…The impact of comorbidities is supported by a study from Sweden, where 30‐day all‐cause mortality was 17% in liver transplant recipients and 9.3% in kidney transplant recipients, and in this study liver transplant recipients had a higher burden of comorbidities 2 . Finally, we previously found kidney transplant recipients to develop less robust antibody responses to BNT162b2 vaccination than liver transplant recipients 18 . Robust antibody responses have been shown to be of importance in protection against disease progression, 49 inferring that differences in immunological responses between kidney and liver transplant recipients may be of importance.…”

“… 2 Finally, we previously found kidney transplant recipients to develop less robust antibody responses to BNT162b2 vaccination than liver transplant recipients. 18 Robust antibody responses have been shown to be of importance in protection against disease progression, 49 inferring that differences in immunological responses between kidney and liver transplant recipients may be of importance.…”

“…Reports suggest that in the first months after vaccination, SARS‐CoV‐2 vaccines effectively protect SOT recipients against infections. 12 , 13 , 14 However, humoral immunity wanes over time in both immunocompetent individuals 15 , 16 and SOT recipients, 17 , 18 and a higher proportion of SOT recipients reach low concentrations of antibodies and neutralizing capacity of antibodies 6 months after vaccination than immunocompetent individuals. 18 Furthermore, reports showing that protection against infection wanes over time in immunocompetent individuals 10 , 19 , 20 , 21 have led to administration of a third and, subsequently, a fourth vaccine dose to SOT recipients in many countries.…”

“…[12][13][14] However, humoral immunity wanes over time in both immunocompetent individuals 15,16 and SOT recipients, 17,18 and a higher proportion of SOT recipients reach low concentrations of antibodies and neutralizing capacity of antibodies 6 months after vaccination than immunocompetent individuals. 18 Furthermore, reports showing that protection against infection wanes over time in immunocompetent individuals 10,[19][20][21] have led to administration of a third and, subsequently, a fourth vaccine dose to SOT recipients in many countries. 9 After vaccination, SOT recipients remain at higher risk of SARS-CoV-2 infections than immunocompetent individuals.…”

What is New in Prophylaxis and Treatment of Covid- 19 in Renal Transplant Patients?

“…Interesting data are also documented by the already cited study of Hamm (5). Previous studies had already documented a reduced humoral response after two vaccine doses in SOT recipients (18,19,20,21).…”