key: cord-0968747-q2ulpbbm
authors: Alejo, Jennifer L.; Mitchell, Jonathan; Chiang, Teresa P.-Y.; Abedon, Aura T.; Boyarsky, Brian J.; Avery, Robin K.; Tobian, Aaron A.R.; Levan, Macey L.; Massie, Allan B.; Garonzik-Wang, Jacqueline M.; Segev, Dorry L.; Werbel, William A.
title: Antibody Response to a Fourth Dose of a SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case Series
date: 2021-08-24
journal: Transplantation
DOI: 10.1097/tp.0000000000003934
sha: 7c445cdd9492eec4ae682c5d7f5d1ef6af47354f
doc_id: 968747
cord_uid: q2ulpbbm

Supplemental Digital Content is available in the text.

T he antibody response after 2 doses of an mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine is excellent in the general population but less robust in transplant patients. 1 Severe breakthrough infections in solid organ transplant recipients (SOTRs) have prompted debate on how to protect these individuals. 2, 3 We previously reported improved antibody responses in ~50% of SOTRs after a third dose (D3) of vaccine. 4 In this series, we studied antibody responses to a fourth dose (D4) of SARS-CoV-2 vaccine in 18 SOTRs from April 24, 2021, through June 16, 2021.

Participants were enrolled in an observational study of SARS-CoV-2 vaccination outcomes in SOTRs. 1 Eighteen received a D4 of a coronavirus disease 2019 vaccine and had no known history of COVID-19 infection. Semiquantitative antispike antibody testing was performed using the Roche Elecsys anti-SARS-CoV-2 S or the EUROIMMUN immunoglobulin G enzyme immunoassays 2-6 wk post-D4. We categorized titers as negative, low-positive, and high-positive; low-positive titers were >0.8 U/mL but <50 U/mL (Roche), or >1.1 but <4 AU (EUROIMMUN). High-positive titers were ≥50 U/mL (Roche) or ≥4 AU (EUROIMMUN). This study was approved by the Johns Hopkins Institutional Review Board and participants provided informed consent electronically.

The median age was 58 y (interquartile range [IQR], 50-65). The median time from transplant was 7.1 y (IQR, 2.3-16.2). The median time from D3 to D4 was 28 d (IQR, 21-30). Eleven (61.1%) participants received kidney transplants. Sixteen (88.9%) were on mycophenolate mofetil at the time of vaccination. Pre-D4, there were 6 participants with negative titers, 2 with low-positive, and 10 with high-positive. Post-D4, 5 of 8 (63%) participants with negative or low-positive titers showed boosting to high-positive titers (Table 1) . Additionally, among 11 SOTRs serially tested on similar assays, post-D4 titers rose in 7 (63%). Most participants with high-positive pre-D4 titers showed further boosting. The 3 participants with persistently negative titers post-D4 were kidney transplant recipients <5 y posttransplant taking tacrolimus and mycophenolate mofetil, and 2 of 3 were additionally taking corticosteroids. Eleven of 16 participants (69%) receiving antiproliferative agents showed antibody boosting.

To our knowledge, this is the first series describing the antibody response among SOTRs after 4 doses of vaccine against COVID-19. Given neutralizing antibody level may be the best correlate of vaccine-associated immunoprotection to date, it is encouraging that 50% of participants with negative and all with low-positive titers pre-D4 showed boosting to high-positive titers post-D4. 5 This echoes previous findings that one-third of negative and all low-positive patients after 2 doses were boosted to highpositive titers after receiving a D3 of vaccine. 4 These findings suggest that immunogenic potential exists for these poor responders.

Limitations include small sample size, lack of formal neutralizing antibody, B-cell or T-cell assays, durability of antibody levels, or safety information regarding the D4 given limited time to follow-up. We also lacked CD4 counts or hypogammaglobulinemia information in persistent suboptimal responders. 

Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients

Severe consequences of COVID-19 infection among vaccinated kidney transplant recipients

Risk of breakthrough SARS-CoV-2 infections in adult transplant recipients

Safety and immunogenicity of a third dose of SARS-CoV-2 vaccine in solid organ transplant recipients: a case series

Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection

The authors thank the participants of the study, without whom this work would be impossible, as well as the Johns Hopkins Transplant Vaccine study team, including Michael T. Ou, BS; Ross S. Greenberg, BA; Jake A. Ruddy, BS; Muhammad Asad Munir, MBBS; Michelle R. Krach, MS; Iulia Barbur, BSE. They also thank Andrew H. Karaba, MD, PhD; and Ms. Yolanda Eby for project support and guidance.