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. 2022 Feb 23:13:832501.
doi: 10.3389/fimmu.2022.832501. eCollection 2022.

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

Sebastian Rask Hamm  1 , Dina Leth Møller  1 , Laura Pérez-Alós  2 , Cecilie Bo Hansen  2 , Mia Marie Pries-Heje  3 , Line Dam Heftdal  1   4 , Rasmus Bo Hasselbalch  5 , Kamille Fogh  5 , Johannes Roth Madsen  2 , Jose Juan Almagro Armenteros  6 , Andreas Dehlbæk Knudsen  1 , Johan Runge Poulsen  1 , Ruth Frikke-Schmidt  7   8 , Linda Maria Hilsted  7 , Erik Sørensen  9 , Sisse Rye Ostrowski  8   9 , Zitta Barrella Harboe  8   10 , Michael Perch  3   8 , Søren Schwartz Sørensen  8   11 , Allan Rasmussen  12 , Henning Bundgaard  3   8 , Peter Garred  2   8 , Kasper Iversen  5   8   13 , Susanne Dam Nielsen  1   8   12
Affiliations

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

Sebastian Rask Hamm et al. Front Immunol. .

Abstract

Background: Previous 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.

Methods: We 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.

Results: In 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).

Conclusion: Immune 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.

Keywords: BNT162b2; COVID-19; SARS-CoV-2; immunogenicity; solid organ transplant recipient; vaccination; vaccine.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Observed anti-receptor-binding domain (RBD) immunoglobulin G (IgG) concentrations and predicted geometric mean concentration (GMC) of anti-RBD in solid organ transplant (SOT) recipients and controls. Development in predicted GMC of anti-RBD IgG represented in AU/ml plotted on top of the observed individual concentration of anti-RBD IgG at each sample time from SOT recipients (yellow) and controls (blue). The dashed horizontal line indicates the minimum threshold for positive humoral response.
Figure 2
Figure 2
Observed anti-receptor-binding domain (RBD) immunoglobulin G (IgG) concentration and predicted geometric mean concentration (GMC) of anti-RBD IgG in solid organ transplant (SOT) recipients and controls. Development in predicted anti-RBD IgG concentration represented in AU/ml plotted on top of the observed individual concentration of anti-RBD IgG from the day of the first vaccination to 228 days after the first vaccination from SOT recipients (yellow) and controls (blue). The dashed horizontal line indicates the minimum threshold for positive humoral response.
Figure 3
Figure 3
Observed neutralizing capacity and predicted mean neutralizing capacity in solid organ transplant (SOT) recipients and controls. Development in predicted mean neutralizing capacity represented in percent plotted on top of the observed individual neutralizing capacity at each sample time from SOT recipients (yellow) and controls (blue). The dashed horizontal line indicates the minimum threshold for positive humoral response.
Figure 4
Figure 4
Observed anti-receptor-binding domain (RBD) immunoglobulin G (IgG) concentrations and predicted geometric mean concentration (GMC) of anti-RBD in liver, kidney, and lung transplant recipients. Development in predicted GMC of anti-RBD IgG represented in AU/ml plotted on top of the observed individual concentration of anti-RBD IgG at each sample time in liver (green/triangle), kidney (yellow/circle), and lung transplant recipients (brown/square). The dashed horizontal line indicates the minimum threshold for positive humoral response.
Figure 5
Figure 5
Observed neutralizing capacity and predicted mean neutralizing capacity in liver, kidney, and lung transplant recipients. Development in predicted mean neutralizing capacity represented in percent plotted on top of the observed individual neutralizing capacity at each sample time from liver (green/triangle), kidney (yellow/circle), and lung transplant recipients (brown/square). The dashed horizontal line indicates the minimum threshold for positive humoral response.
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