Antibody Response to a Fourth Dose of a SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case Series : Transplantation

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Antibody Response to a Fourth Dose of a SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case Series

Alejo, Jennifer L. MD1; Mitchell, Jonathan MBBS1; Chiang, Teresa P.-Y. MD, MPH1; Abedon, Aura T. BS1; Boyarsky, Brian J. MD, PhD1; Avery, Robin K. MD2; Tobian, Aaron A.R. MD, PhD3; Levan, Macey L. JD, PhD1; Massie, Allan B. PhD1; Garonzik-Wang, Jacqueline M. MD, PhD1; Segev, Dorry L. MD, PhD1; Werbel, William A. MD2

Author Information
doi: 10.1097/TP.0000000000003934

Abstract

Erratum

In the article “Antibody Response to a Fourth Dose of a SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case Series” by Alejo et al in the December 2021 issue of Transplantation, Table 1, Row 12 (68 Male) Post-D3 Titer (Column 10) should read “402.9” and Post-D4 titer (Column 13) should read “>2500.”

Transplantation. 106(2):e177, February 2022.

The 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 (COVID-19) 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.

TABLE 1. - Antibody titers after each vaccine
Age, y Sex Organ(s) Time since transplant, y Antimetabolite Initial vaccine series Post-D2 titer D3 Post-D3 titer Post-D3 titer D4 Post-D4 titer Post-D4 titer
44 F Kidney 4 Yes Moderna Negative Pfizer Negative 0.22 E Pfizer Negative 0.92 E
65 F Kidney 0.5 Yes Moderna Negative Moderna Negative 0.06 E Moderna Negative 0.06 E
44 M Kidney 3 Yes Pfizer Negative Pfizer Negative 0.09 E J&J Negative 0.4 R
63 M Liver 11 Yes Pfizer Negative J&J Negative 0.46 R Pfizer High 54.9 R
57 M Kidney 15 Yes J&J Negative Moderna Negative 0.97 E Moderna High 286.9 R
53 M Kidney 21 Yes Pfizer Negative Pfizer Negative (self-report) J&J High 343 R
61 F Kidney 8 Yes Pfizer Negative Moderna Low 2.75 R Moderna High >2500 R
49 F Kidney 1 Yes Moderna Negative Pfizer Low 7.3 R Pfizer High 82.9 R
52 F Kidney-Pancreas 20 Yes Moderna Negative Pfizer High 504.4 R Pfizer High 845 R
54 M Liver 1 Yes Pfizer Low Moderna High 125.7 R Moderna High >2500 R
69 M Heart 16 Yes Pfizer Negative Moderna High 8.37 E Moderna High >2500 R
68 M Heart 2 Yes Pfizer Negative Moderna High >250 R Moderna High 402.9 R
43 F Pancreas 1 Yes Pfizer Negative Moderna High 4.72 E Moderna High 5.27 E
58 M Kidney 3 Yes Moderna Low Moderna High 6.93 E Moderna High 4.16 E
42 F Liver 5 No Moderna Negative Pfizer High 11.39 E Pfizer High 8.75 E
73 F Kidney-Liver 18 Yes Pfizer Low Moderna High 4.45 E Moderna High 1691 R
67 F Kidney 11 Yes Moderna Low Pfizer High 9.19 E Pfizer High >2500 R
64 M Liver 21 No Moderna Low Pfizer High 7.21 E Pfizer High >2500 R
D, dose; E, EUROIMMUN assay (parameters: low-positive, ≥1.1 and <4; high-positive, ≥4 AU); F, female; J&J, Johnson & Johnson; M, male; R, Roche assay (parameters: low-positive, ≥0.8 and <50; high-positive, ≥50 U/mL).

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 high-positive 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.

Though some patients may require additional measures such as immunosuppression modulation to achieve immunity, these data support continued exploration of subsequent vaccine doses in SOTRs.

ACKNOWLEDGEMENTS

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.

REFERENCES

1. Boyarsky BJ, Werbel WA, Avery RK, et al. Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients. JAMA. 2021;325:2204–2206.
2. Tau N, Yahav D, Schneider S, et al. Severe consequences of COVID-19 infection among vaccinated kidney transplant recipients. Am J Transplant. 2021;21:2910–2912.
3. Qin CX, Moore LW, Anjan S, et al. Risk of breakthrough SARS-CoV-2 infections in adult transplant recipients. Transplantation. 2021;105:e265–e266.
4. Werbel WA, Boyarsky BJ, Ou MT, et al. Safety and immunogenicity of a third dose of SARS-CoV-2 vaccine in solid organ transplant recipients: a case series. Ann Intern Med. 2021;174:1330–1332.
5. Khoury DS, Cromer D, Reynaldi A, et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat Med. 2021;27:1205–1211.

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