Impaired Antibody Responses to Spike Protein Antigens of Sars-cov-2 in Solid Organ Transplant (sot) Recipients
1Plexision, pittsburgh, PA, 2Medical University of South Carolina, Charleston, SC, 3MedStar Georgetown Transplant Institute, Georgetown, DC, 4DHR Health Institute for Research and Development, Texas, TX, 5University of Pittsburgh, Pittsburgh, PA
Meeting: 2021 American Transplant Congress
Abstract number: LB 15
Keywords: Antibodies, COVID-19, Immunosuppression, T cell activation
Topic: Clinical Science » Biomarkers, Immune Assessment and Clinical Outcomes
Session Information
Session Name: Late Breaking: Basic & ID
Session Type: Rapid Fire Oral Abstract
Date: Monday, June 7, 2021
Session Time: 6:00pm-7:00pm
Presentation Time: 6:30pm-6:35pm
Location: Virtual
*Purpose: Chronic immunosuppression can impair antibody responses after natural infection and vaccination in SOT recipients. It is not known whether antibody responses are impaired in SOT compared with non-SOT patients with COVID-19
*Methods: We evaluated IgG responses to the spike (S) and receptor binding domain (RBD) antigenic sequences of SARS-CoV-2 after COVID-19-infection in SOT and non-SOT patients using enzyme-linked immunosorbent assay (ELISA). The S protein consists of a conserved C-terminal and less conserved N-terminal S1 sequence which contains the RBD. An optical density (OD) at 490 nm of 0.45 or greater, or < 0.45 was read as positive and negative ELISA result based on pre-clinical validation in 148 subjects. S1-reactive, S2-reactive and S-reactive CD4 cells that expressed CD154 were measured with flow cytometry after overnight stimulation with respective peptide mixtures for these antigens.
*Results: 204 total study subjects, mean+/-SD age 47.5+/-21 years, were sampled at mean 12.6 (range 0-94) days after diagnosis. Subjects included 107 males, 74 SOT (liver-48, kidney-26) and 130 non-SOT. Among them, 103 patients with COVID-19 included 32 SOT and 71 non-SOT. Antibody measurements were performed in 74 COVID-19 patients. Fifty one of 74 patients received convalescent plasma. Anti-spike and anti-RBD IgG were present in 49 of 51 (96%) and 47 of 51 (92%) patients, respectively. Among the remaining 23 patients who did not receive plasma, anti-spike IgG and anti-RBD IgG were present in 21 (91%) and 16 (69.5%) patients, respectively. The incidence of anti-RBD IgG was significantly lower in SOT, 2 of 7 or 29%, compared with non-transplant patients, 14 of 16 or 88% (p=0.011). Between-group differences in the incidence of anti-spike IgG were not significant (5/7 or 71% SOT vs 16/16 or 100% SOT, p=NS). One of 23 patients, an SOT recipient died and showed no IgG to S or RBD antigens. Antibody titers reflected in OD490 readings were lower in SOT compared with non-SOT for anti-spike IgG (mean 2.2+/-0.6 vs 1.4+/-1.2, p=0.16, NS) and anti-RBD IgG (1.8+/-0.9 vs 0.54+/-0.7, p=0.004). Subjects without and with anti-RBD antibody did not differ in timing of the sample from diagnosis (mean+/-SD 18+/-12.5 vs 12+/-12, p=0.258, NS, respectively), frequencies of S-, S1 or S2-reactive T-cells (mean 3.1+/-2.4% vs 1.8+/2%, p=0.225, NS, respectively), or proportions of patients requiring intubation (2/7 or 29% vs 4/16 or 25%, p=1.00, NS, respectively).
*Conclusions: Chronically immunosuppressed liver and kidney transplant recipients demonstrated impaired antibody responses to SARS-CoV-2 spike antigens, especially to less conserved RBD-containing viral sequence. This finding may portend impaired vaccine efficacy in transplant recipients.
To cite this abstract in AMA style:
Ashokkumar C, Nadig S, Rohan V, Kroemer A, Dhani H, Rao S, Sindhi R. Impaired Antibody Responses to Spike Protein Antigens of Sars-cov-2 in Solid Organ Transplant (sot) Recipients [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/impaired-antibody-responses-to-spike-protein-antigens-of-sars-cov-2-in-solid-organ-transplant-sot-recipients/. Accessed November 21, 2024.« Back to 2021 American Transplant Congress