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SARS-CoV-2 Infection is Associated with Greater Neutralizing Antibody Response Compared to Three Doses of Mrna-1273 Vaccine in Solid Organ Transplant Recipients

V. H. Ferreira, V. Hall, T. M. Marinelli, M. Ierullo, V. Kulasingam, A. Humar, D. Kumar

University Health Network, Toronto, ON, Canada

Meeting: 2022 American Transplant Congress

Abstract number: 682

Keywords: Antibodies, COVID-19, T cells, Vaccination

Topic: Clinical Science » Infection Disease » 24 - All Infections (Excluding Kidney & Viral Hepatitis)

Session Information

Session Name: All Infections (Excluding Kidney & Viral Hepatitis) I

Session Type: Poster Abstract

Date: Saturday, June 4, 2022

Session Time: 5:30pm-7:00pm

 Presentation Time: 5:30pm-7:00pm

Location: Hynes Halls C & D

*Purpose: Prior studies suggest that two doses of mRNA vaccine in SOTR may result in lower antibody and T-cell responses relative to levels seen following natural SARS-CoV-2 infection. In this study, we evaluated whether three doses of mRNA-1273 vaccine result in immune responses more comparable to, or greater than, natural infection.

*Methods: Serum was collected 4-6 weeks from symptom onset in n=74 SOTR recovered from SARS-CoV-2 infection, and in n=60 SOTR receiving a third dose of mRNA-1273. Disease severity in the infection cohort ranged from mild to severe, but no deaths were reported. Vaccinated SOTR all had negative anti-nucleoprotein antibody results to confirm absence of infection. SARS-CoV-2 serology was assessed using an anti-spike (S) receptor binding domain (RBD) immunoassay (Roche). Neutralizing antibodies (nAb) were assessed using a commercial surrogate virus neutralization test (SVNT) targeting wildtype (WT), alpha, beta and delta strains (GenScript). A subset of participants underwent spike-specific T-cell testing (infection n=50, three doses n=34). PBMCs were stimulated overnight with overlapping peptides and frequencies of S-specific polyfunctional CD4+ and CD8+ T-cells (expressing IFN‐γ and IL‐2) were measured by intracellular cytokine staining. Mann Whitney U, and Chi-square tests were used for statistical comparisons; significance was defined at p<0.05.

*Results: Anti-S RBD antibodies in SOTR recovered from infection were similar to levels in those receiving three doses of mRNA-1273 (median U/mL [IQR]: 73.5 [14.9-240.1] vs. 313.8 [313.8-2191.0]; p=0.17). Relative to SOTR recovered from infection, the proportion of SOTR positive for nAb after three doses of vaccine was significantly lower. This was true for WT (93.2% vs. 60.0%, p<0.0001) and all variants tested - alpha: 90.5% vs. 56.7%, p<0.0001; beta: 67.6% vs. 50%, p=0.039; and delta: 85.1% vs. 55%, p=0.0001. Spike-specific polyfunctional CD4+ T-cell frequencies were similar between infection and three doses of vaccine (median cell frequency [IQR]: 241.7 [50-539.7] vs. 432.4 [50-1226]; p>0.05). Spike-specific polyfunctional CD8+ T-cells were uncommonly detected following infection or vaccination. Vaccinated participants were significantly older than infected SOTR (p<0.001), and some differences in type of transplant were found between groups. However, sex and type of immunosuppressive medications were similar between infected and vaccinated SOTR cohorts (p>0.05).

*Conclusions: Three doses of mRNA vaccine may be required to optimize binding antibody, and to a lesser extent, CD4+ T-cell immunity, to levels similar to natural infection. However, nAb responses to wild-type virus and variants of concern were highest in SOTR recovered from infection when compared to vaccinated patients. These data provide further evidence of impaired SARS-CoV-2 vaccine responses in SOTR.

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To cite this abstract in AMA style:

Ferreira VH, Hall V, Marinelli TM, Ierullo M, Kulasingam V, Humar A, Kumar D. SARS-CoV-2 Infection is Associated with Greater Neutralizing Antibody Response Compared to Three Doses of Mrna-1273 Vaccine in Solid Organ Transplant Recipients [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/sars-cov-2-infection-is-associated-with-greater-neutralizing-antibody-response-compared-to-three-doses-of-mrna-1273-vaccine-in-solid-organ-transplant-recipients/. Accessed May 28, 2025.

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