Antibody Response to an mRNA SARS-CoV-2 Vaccine Following Initial Vaccination With Ad.26.COV2.S in Solid Organ Transplant Recipients: A Case Series : Transplantation

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Antibody Response to an mRNA SARS-CoV-2 Vaccine Following Initial Vaccination With Ad.26.COV2.S in Solid Organ Transplant Recipients: A Case Series

Chang, Amy MD1; Alejo, Jennifer L. MD1; Abedon, Aura T. BS1; Mitchell, Jonathan MBBS1,2; Chiang, Teresa P.-Y. MD, MPH1; Boyarsky, Brian J. MD, PhD1; Avery, Robin K. MD3; Tobian, Aaron A.R. MD, PhD3; Levan, Macey L. JD, PhD1,4; Warren, Daniel S. PhD1; Massie, Allan B. PhD, MHS1; Garonzik-Wang, Jacqueline M. MD, PhD5; Segev, Dorry L. MD, PhD1,6; Werbel, William A. MD3

Author Information

1 Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.

2 Department of Surgery, Howard University College of Medicine, Washington, DC.

3 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.

4 Department of Acute and Chronic Care, Johns Hopkins University School of Nursing, Baltimore, MD.

5 Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI.

6 Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD.

Received 9 October 2021. Accepted 14 October 2021.

A.C. and J.L.A. contributed equally to this article.

Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work: A.C., J.L.A., A.T.A., J.M., T.P.-Y.C., B.J.B., R.K.A., A.A.R.T., M.L.L., D.S.W., A.B.M., J.M.G.-W., D.L.S., and W.A.W. Drafting the work of revising it critically for important intellectual content: Final approval of the version to be published: A.C., J.L.A., A.T.A., J.M., T.P.-Y.C., B.J.B., R.K.A., A.A.R.T., M.L.L., D.S.W., A.B.M., J.M.G.-W., D.L.S., and W.A.W. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: A.C., J.L.A., A.T.A., J.M., T.P.-Y.C., B.J.B., R.K.A., A.T., M.L.L., D.S.W., A.B.M., J.M.G.-W., D.L.S., and W.A.W.

This research was made possible with the generous support of the Ben-Dov family. This work was supported by grants T32DK007713 (J.L.A.), the ASTS Fryer Resident Scientist Award (J.M.), T32DK007732 (A.C.), F32DK124941 (B.J.B.), K01DK114388-03 (M.L.L.), K01DK101677 (A.B.M.), and K23DK115908 (J.M.G.-W) from the National Institute of Diabetes and Digestive and Kidney Diseases; K23AI157893 (W.A.W.) and K24AI144954 (D.L.S.) from the National Institute of Allergy and Infectious Disease. The analyses described here are the sole responsibility of the authors and do not necessarily reflect the views or policies of the Department of Health and Human Services or the National Institutes of Health, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government.

Dr Segev has the following financial disclosures: consulting and speaking honoraria from Sanofi, Novartis, CLS Behring, Jazz Pharmaceuticals, Veloxis, Mallinckrodt, and Thermo Fisher Scientific. Dr Avery has study/grant support from Aicuris, Astellas, Chimerix, Merck, Oxford Immunotec, Qiagen, Regeneron, Takeda/Shire, and Vir/GSK, and is an associate editor for Transplantation. Dr Levan is the Social Media Editor for Transplantation. The other authors declare no conflicts of interest.

Correspondence: Dorry Segev, MD, PhD, Department of Surgery, Johns Hopkins Medical Institutions, Epidemiology Research Group in Organ Transplantation, 2000 E Monument St, Baltimore, MD 21205. ([email protected]).

Transplantation 106(2):p e161-e162, February 2022. | DOI: 10.1097/TP.0000000000003991
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Solid organ transplant recipients (SOTRs) have 89% lower odds of an anti-spike antibody response to Ad.26.COV2.S (Janssen/Johnson & Johnson) coronavirus disease 2019 (COVID-19) vaccination compared to recipients of a 2-dose mRNA vaccine series (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]).1,2 A third dose of mRNA or adenovirus vaccine increases antibody response in mRNA-vaccinated SOTRs, yet there is no available data on safety or efficacy of additional vaccine doses following the primary single-dose Ad.26.COV2.S vaccine.3-5 In this case series from our observational study, we describe antibody responses in Ad.26.COV2.S vaccinated SOTRs (D1) who reported receiving a subsequent mRNA vaccination (D2).

Between March 5, 2021, and August 24, 2021, 7 SOTRs reported receiving Ad.26.COV2.S followed by a subsequent mRNA vaccine (obtained independently; not provided by the study team). None of them reported a prior diagnosis of COVID-19. Antibody titers were assessed 4 to 12 wk after each vaccination using the Roche Elecsys anti–severe acute respiratory syndrome coronavirus 2 enzyme immunoassay or EUROIMMUN enzyme immunoassay as previously reported.1-3 Questionnaires assessing side effects and major adverse events were distributed 7 d postvaccination. This study was approved by the Johns Hopkins Institutional Review Board (IRB00248540).

The median (interquartile range) age was 42 (39–50) y. Most participants were female (n = 5, 71%) and Caucasian (n = 5, 71%) with a median (interquartile range) time of 9 (5–15) y from transplantation. All participants reported taking at least 2 immunosuppressive medications, most commonly calcineurin inhibitors or antimetabolites. Post-D1 titers were negative in 4 (57%) and positive in 3 (43%) participants. Additional vaccines included mRNA-1273 (n = 4, 57.1%) or BNT162b2 (n = 3, 43%) at a median of 2.5 (2.4–4.4) mo after D1. Post-D2, 5 (71%) participants had titers in the positive range. Of these, 3 participants with positive post-D1 antibody levels demonstrated titer boosting to ≥2500 units/mL (upper assay limit). Two participants showed de novo seroconversion post-D2. Two had persistently negative titers post-D2 (Table 1).

TABLE 1. - SOTRs who received Ad.26.COV2.S and any subsequent vaccinations
Age Sex Race Allograft Years Since Transplant IS Regimen Dose 1 Highest Post-D1 Antibody Level Dose 2 Highest Post-D2 Antibody Level Months Between Doses Symptoms Post-D2
40 F C Kidney 9 Sirolimus azathioprine Ad.26.COV2.S 115 R mRNA-1273 ≥2500 R 2.0 –
31 F AA Kidney 5 Tacrolimus MMF Ad.26.COV2.S Neg Ra BNT162b2 0.05 E 2.3 Mild pain mild swelling
58 M C Kidney 15 Tacrolimus MMF Ad.26.COV2.S 0.40 R mRNA-1273 0.97 E 2.4 Moderate pain
42 F C Liver 0.4 Tacrolimus MMF corticosteroid Ad.26.COV2.S 0.4 R mRNA-1273 6.5 R 2.5 Mild pain, moderate fatigue
38 F C Kidney 8 Tacrolimus MMF corticosteroid Ad.26.COV2.S 0.60 R BNT162b2 531 R 3.2 Mild pain mild fatigue
42 F H Kidney 13 Tacrolimus azathioprine Ad.26.COV2.S 283 R BNT162b2 ≥2500 R 5.6 –
67 M C Kidney 19 Tacrolimus MMF corticosteroid Ad.26.COV2.S 4.90 R mRNA-1273 ≥2500 R 5.7 –
Positive sero-response cutoff: >0.8 U/mL (Roche); >1.1 AU (EUROIMMUN).
aSelf-reported assay (titer not available).
AA, African American; C, Caucasian; D1, dose 1; D2, dose 2; F, female; H, Hispanic; IS, immunosuppression; M, male; MMF, mycophenolate mofetil; SOTR, solid organ transplant recipient.

Four participants completed the safety questionnaire 1–5 wk post-D2. Local side effects included mild or moderate pain and swelling. Fatigue was the only reported systemic side effect. No acute rejection, incident infections, neurological or autoimmune conditions, or hospitalization were reported.

Limitations include small sample size, low rate of questionnaire response, lack of B- and T-cell testing, and virus neutralization studies. Additionally, COVID-19 diagnoses were self-reported and therefore subject to reporting bias.

In conclusion, this case series describes preliminary safety of and antibody responses to single mRNA vaccination following Ad.26.COV2.S vaccination in SOTRs. Five of 7 patients experienced boosting of antibody levels, 2 of whom were seronegative before receiving a second vaccine. Two had persistently negative titers after D2. There were no reported serious short-term safety concerns. Subsequent mRNA dosing resulted in robust immunogenicity in those with preceding positive antibody titers, whereas participants with negative antibody levels after receiving Ad.26.COV2.S showed variable responses to subsequent mRNA vaccines. Given then low immunogenicity of a single-dose Johnson & Johnson vaccine in this high-risk population, further investigation into heterologous prime-boost strategies is warranted to optimize protection for SOTRs.

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. Boyarsky BJ, Chiang TP-Y, Ou MT, et al. Antibody response to the Janssen COVID-19 vaccine in solid organ transplant recipients. Transplantation. 2021;105:e82–e83.
3. 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.
4. Hall VG, Ferreira VH, Ku T, et al. Randomized trial of a third dose of mRNA-1273 vaccine in transplant recipients. N Engl J Med. 2021;385:1244–1246.
5. Schmidt T, Klemis V, Schub D, et al. Cellular immunity predominates over humoral immunity after homologous and heterologous mRNA and vector-based COVID-19 vaccine regimens in solid organ transplant recipients. Am J Transplant. 2021;21:3990–4002.
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