A Third Dose of SARS-CoV-2 Vaccine Increases Neutralizing Antibodies Against Variants of Concern in Solid Organ Transplant Recipients

Andrew H. Karaba; Xianming Zhu; Tao Liang; Kristy H. Wang; Alex G. Rittenhouse; Olivia Akinde; Yolanda Eby; Jessica E. Ruff; Joel N. Blankson; Aura T. Abedon; Jennifer L. Alejo; Andrea L. Cox; Justin R. Bailey; Elizabeth A. Thompson; Sabra L. Klein; Daniel S. Warren; Jacqueline M. Garonzik-Wang; Brian J. Boyarsky; Ioannis Sitaras; Andrew Pekosz; Dorry L. Segev; Aaron A.R. Tobian; William A. Werbel


American Journal of Transplantation. 2022;22(4):1253-1260. 

In This Article

Abstract and Introduction


Vaccine-induced SARS-CoV-2 antibody responses are attenuated in solid organ transplant recipients (SOTRs) and breakthrough infections are more common. Additional SARS-CoV-2 vaccine doses increase anti-spike IgG in some SOTRs, but it is uncertain whether neutralization of variants of concern (VOCs) is enhanced. We tested 47 SOTRs for clinical and research anti-spike IgG, pseudoneutralization (ACE2 blocking), and live-virus neutralization (nAb) against VOCs before and after a third SARS-CoV-2 vaccine dose (70% mRNA, 30% Ad26.COV2.S) with comparison to 15 healthy controls after two mRNA vaccine doses. We used correlation analysis to compare anti-spike IgG assays and focused on thresholds associated with neutralization. A third SARS-CoV-2 vaccine dose increased median total anti-spike (1.6-fold), pseudoneutralization against VOCs (2.5-fold vs. Delta), and neutralizing antibodies (1.4-fold against Delta). However, neutralization activity was significantly lower than healthy controls (p < .001); 32% of SOTRs had zero detectable nAb against Delta after third vaccination compared to 100% for controls. Correlation with nAb was seen at anti-spike IgG >4 Log10(AU/ml) on the Euroimmun ELISA and >4 Log10(AU/ml) on the MSD research assay. These findings highlight benefits of a third vaccine dose for some SOTRs and the need for alternative strategies to improve protection in a significant subset of this population.


Solid organ transplant recipients (SOTRs) are at increased risk for severe COVID-19.[1,2] Therefore, effective and optimized vaccines that prevent COVID-19 disease in this group are critical. Unfortunately, these patients were excluded from the phase III SARS-CoV-2 vaccines trials;[3,4] recent publications suggest that breakthrough disease is more common among fully-vaccinated SOTRs than the general population.[5,6] Furthermore, given many SOTRs develop weak SARS-CoV-2 antibody responses after two doses of an mRNA-based vaccine,[7–10] third doses have been authorized for immunocompromised persons in multiple countries. Yet, published data on neutralizing capacity of SOTR plasma after additional vaccine doses are limited.[11–13] In particular, it is unknown if a third vaccine dose would result in protection against more transmissible variants of concern (VOCs) that exhibit immune escape, including the Delta variant which currently comprises >99% of new cases in the United States.[14] To assess whether a third dose of SARS-CoV-2 vaccine in SOTRs would improve the SARS-CoV-2-specific neutralizing response, we measured total SARS-CoV-2-specific IgG and neutralizing activity using pseudoneutralization and live-virus assays against the vaccine strain and VOCs before and after a third dose of SARS-CoV-2 vaccine and compared this to vaccinated healthy controls (HC).