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

Abstract

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 neutralizing activity. A third SARS-CoV-2 vaccine dose increased median anti-spike (1.6-fold) and receptor-binding domain (1.5-fold) IgG, as well as pseudoneutralization against VOCs (2.5-fold versus Delta). However, IgG and neutralization activity were significantly lower than healthy controls (p<0.001); 32% of SOTRs had zero detectable nAb against Delta after third vaccination. Correlation with nAb was seen at anti-spike IgG >4 AU on the clinical assay and >10^4 AU on the 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.

• Authors: 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
• Journal: medRxiv : the preprint server for health sciences (medRxiv) (Oct 13 2021) United States
• PMID: 34671774 (Publication Type: Preprint)