AUTHOR=Hamm Sebastian Rask , Møller Dina Leth , Pérez-Alós Laura , Hansen Cecilie Bo , Pries-Heje Mia Marie , Heftdal Line Dam , Hasselbalch Rasmus Bo , Fogh Kamille , Madsen Johannes Roth , Almagro Armenteros Jose Juan , Knudsen Andreas Dehlbæk , Poulsen Johan Runge , Frikke-Schmidt Ruth , Hilsted Linda Maria , Sørensen Erik , Ostrowski Sisse Rye , Harboe Zitta Barrella , Perch Michael , Sørensen Søren Schwartz , Rasmussen Allan , Bundgaard Henning , Garred Peter , Iversen Kasper , Nielsen Susanne Dam TITLE=Decline in Antibody Concentration 6 Months After Two Doses of SARS-CoV-2 BNT162b2 Vaccine in Solid Organ Transplant Recipients and Healthy Controls JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.832501 DOI=10.3389/fimmu.2022.832501 ISSN=1664-3224 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.