Published online Jun 18, 2024. doi: 10.13105/wjma.v12.i2.91264
Revised: April 18, 2024
Accepted: June 7, 2024
Published online: June 18, 2024
Processing time: 167 Days and 23.7 Hours
Vaccination against Coronavirus disease-19 (COVID-19) was pivotal to limit spread, morbidity and mortality. Our aim is to find out whether vaccines against COVID-19 lead to an immunological response stimulating the production of de novo donor specific antibodies (DSAs) or increase in mean fluorescence intensity (MFI) of pre-existing DSAs in kidney transplant recipients (KTRs). This study involved a detailed literature search through December 2nd, 2023 using PubMed as the primary database. The search strategy incorporated a combination of relevant Medical Subject Headings terms and keywords: "COVID-19", "SARS-CoV-2 Vaccination", "Kidney, Renal Transplant", and "Donor specific antibodies". The results from related studies were collated and analyzed. A total of 6 studies were identified, encompassing 460 KTRs vaccinated against COVID-19. Immunological responses were detected in 8 KTRs of which 5 had increased MFIs, 1 had de novo DSA, and 2 were categorized as either having de novo DSA or increased MFI. There were 48 KTRs with pre-existing DSAs prior to vaccination, but one study (Massa et al) did not report whether pre-existing DSAs were associated with post vaccination outcomes. Of the remaining 5 studies, 35 KTRs with pre-existing DSAs were identified of which 7 KTRs (20%) developed de novo DSAs or increased MFIs. Overall, no immunological response was detected in 452 (98.3%) KTRs. Our study affirms prior reports that COVID-19 vaccination is safe for KTRs, especially if there are no pre-existing DSAs. However, if KTRs have pre-existing DSAs, then an increased immunological risk may be present. These findings need to be taken cautiously as they are based on a limited number of patients so further studies are still needed for confirmation.
Core Tip: Our aim was to find out whether vaccines against Coronavirus disease 2019 (COVID-19) lead to an immunological response stimulating the production of de novo donor specific antibodies (DSAs) or increase in mean fluorescence intensity of pre-existing DSAs in kidney transplant recipients. We did a detailed literature search through December 2, 2023 using PubMed as the primary database. We used the following keywords: COVID-19, severe acute respiratory syndrome-coronavirus-2 vaccination, Kidney, Renal transplant, and DSAs. The results from related studies were collated and analyzed.
- Citation: Daoud A, Soliman K, Posadas Salas MA, Vaishnav S, Uehara G, Abdelkader A, Fulop T, Casey MJ. Development of donor specific antibodies after SARS-CoV-2 vaccination: What do we know so far? World J Meta-Anal 2024; 12(2): 91264
- URL: https://www.wjgnet.com/2308-3840/full/v12/i2/91264.htm
- DOI: https://dx.doi.org/10.13105/wjma.v12.i2.91264
Vaccination against Severe acute respiratory syndrome–coronavirus–2 (SARS-CoV-2) was pivotal to limit spread, morbidity and mortality of Coronavirus disease-19 (COVID-19), ensuring a high rate of protective antibody formation in the general population[1,2]. Solid organ transplant recipients (SOTRs) are maintained on lifelong immunosuppression to reduce the risk of cellular and antibody mediated rejections. Unfortunately, immunosuppression therapy may also lead to increased COVID-19 mortality among SOTRs[3,4], Since the introduction of the vaccination programs against SARS-CoV-2, vaccinating immunocompromised patients, including SOTRs has been considered as a priority[5].
The presence of anti-human leukocytic antigen (anti-HLA) donor specific antibodies (DSAs) is associated with antibody mediated rejection[6,7]. Do vaccines against SARS-CoV-2 accentuate an immunological response stimulating the production of anti-HLA DSA in kidney transplant recipients (KTRs)?
To answer this question, we conducted a detailed literature review, using PubMed as the primary database, with the search being completed by December 2nd, 2023. The search strategy incorporated a combination of relevant Medical Subject Headings terms and keywords: "COVID-19", "SARS-CoV-2 Vaccine", "Kidney, Renal Transplant" and "Donor Specific Antibodies". The results from related studies were collated and analyzed.
Six unrelated articles that were mainly discussing safety, efficacy and response to COVID vaccines in KTRs.
One article described DSA formation, but was confounded by KTRs being hospitalized with an active COVID-19 infection[8].
This left us with 2 case reports and 7 studies. Abu-Khader et al[9] reported a case of 42-year-old who developed de novo DSAs and de novo anti-HLA non-DSAs after first dose of mRNA based COVID vaccine. Kim et al[10] reported a successful ABO-incompatible living donor kidney transplant in a patient who developed class I DSAs after COVID-19 vaccination.
There were 6 studies evaluating the development of DSAs after COVID vaccination, encompassing 460 KTRs vaccinated against COVID-19. Immunological responses were detected in 8 KTRs of which 5 had increased mean fluorescence intensity (MFI), 1 had de novo DSA, and 2 were categorized as either having de novo DSA or increased MFI[11-15]. There were 48 KTRs with pre-existing DSAs prior to vaccination, but one study (Massa et al[16]) did not report whether pre-existing DSAs were associated with post vaccination outcomes. Of the remaining 5 studies, 35 KTRs with pre-existing DSAs were identified of which 7 KTRs (20%) developed de novo DSAs or increased MFIs (Table 1). Overall, no immunological response was detected in 452 (98.3%) KTRs.
Ref. | Number of patients vaccinated | Number of patients with pre-existing DSAs before vaccination | Type of vaccine | Number of patients who developed de novo DSAs | Number of patients with pre-existing DSAs who developed new DSAs or increased MFI post-vaccine |
McCune et al[11] | 100 | 5 | Moderna 64 Pfizer 36 | 0 | 2 (Unreported whether new DSA or increased MFI) |
Kueht et al[12] | 96 | 16 | Moderna Pfizer J and J | 0 | 5 (All had increased MFIs) |
Al Jurdi et al[13] | 58 | 5 | Moderna Pfizer | 0 | 0 |
Russo et al[14] | 82 | 1 | Pfizer | 0 | 0 |
Nishida et al[15] | 63 | 8 | mRNA vaccine (Moderna and/or Pfizer) | 0 | 0 |
Massa et al[16] | 61 | 13 | Pfizer | 1 | Not reported |
Total | 460 | 48 | 1 | 7 |
The findings of these studies are summarized in Table 1.
In conclusion, our study affirms prior reports that COVID-19 vaccination is safe for KTRs, especially if there are no pre-existing DSAs. However, if KTRs have pre-existing DSAs, then an increased immunological risk may be present. These findings need to be taken cautiously as they are based on a limited number of patients so further studies are still needed for confirmation.
1. | Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, Diemert D, Spector SA, Rouphael N, Creech CB, McGettigan J, Khetan S, Segall N, Solis J, Brosz A, Fierro C, Schwartz H, Neuzil K, Corey L, Gilbert P, Janes H, Follmann D, Marovich M, Mascola J, Polakowski L, Ledgerwood J, Graham BS, Bennett H, Pajon R, Knightly C, Leav B, Deng W, Zhou H, Han S, Ivarsson M, Miller J, Zaks T; COVE Study Group. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2021;384:403-416. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 7073] [Cited by in F6Publishing: 6952] [Article Influence: 2317.3] [Reference Citation Analysis (1)] |
2. | Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, Perez JL, Pérez Marc G, Moreira ED, Zerbini C, Bailey R, Swanson KA, Roychoudhury S, Koury K, Li P, Kalina WV, Cooper D, Frenck RW Jr, Hammitt LL, Türeci Ö, Nell H, Schaefer A, Ünal S, Tresnan DB, Mather S, Dormitzer PR, Şahin U, Jansen KU, Gruber WC; C4591001 Clinical Trial Group. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020;383:2603-2615. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 10556] [Cited by in F6Publishing: 9926] [Article Influence: 2481.5] [Reference Citation Analysis (1)] |
3. | Alfishawy M, Elbendary A, Mohamed M, Nassar M. COVID-19 Mortality in Transplant Recipients. Int J Organ Transplant Med. 2020;11:145-162. [PubMed] [Cited in This Article: ] |
4. | Caldara R, Maffi P, Costa S, Bazzigaluppi E, Brigatti C, Lampasona V, Magistretti P, Manenti F, Marzinotto I, Pellegrini S, Scavini M, Secchi A, Piemonti L. COVID-19 in Solid Organ Transplant Recipient: Exploring Cumulative Incidence, Seroprevalence and Risk Factors for Disease Severity. Biology (Basel). 2021;10. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 1] [Reference Citation Analysis (0)] |
5. | Negahdaripour M, Shafiekhani M, Moezzi SMI, Amiri S, Rasekh S, Bagheri A, Mosaddeghi P, Vazin A. Administration of COVID-19 vaccines in immunocompromised patients. Int Immunopharmacol. 2021;99:108021. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 19] [Cited by in F6Publishing: 44] [Article Influence: 14.7] [Reference Citation Analysis (0)] |
6. | Aubert O, Loupy A, Hidalgo L, Duong van Huyen JP, Higgins S, Viglietti D, Jouven X, Glotz D, Legendre C, Lefaucheur C, Halloran PF. Antibody-Mediated Rejection Due to Preexisting versus De Novo Donor-Specific Antibodies in Kidney Allograft Recipients. J Am Soc Nephrol. 2017;28:1912-1923. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 195] [Cited by in F6Publishing: 188] [Article Influence: 26.9] [Reference Citation Analysis (0)] |
7. | Yue W, Liu J, Li X, Wang L, Li J. Memory B cells and long-lived plasma cells in AMR. Ren Fail. 2022;44:1604-1614. [PubMed] [DOI] [Cited in This Article: ] [Cited by in F6Publishing: 3] [Reference Citation Analysis (0)] |
8. | Killian JT Jr, Houp JA, Burkholder GA, Roman Soto SA, Killian AC, Ong SC, Erdmann NB, Goepfert PA, Hauptfeld-Dolejsek V, Leal SM Jr, Zumaquero E, Nellore A, Agarwal G, Kew CE, Orandi BJ, Locke JE, Porrett PM, Levitan EB, Kumar V, Lund FE. COVID-19 Vaccination and Remdesivir are Associated With Protection From New or Increased Levels of Donor-Specific Antibodies Among Kidney Transplant Recipients Hospitalized With COVID-19. Transpl Int. 2022;35:10626. [PubMed] [DOI] [Cited in This Article: ] [Reference Citation Analysis (0)] |
9. | Abu-Khader A, Wang W, Berka M, Galaszkiewicz I, Khan F, Berka N. SARS Cov-2 vaccination induces de novo donor-specific HLA antibodies in a renal transplant patient on waiting list: A case report. HLA. 2022;99:25-30. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 5] [Cited by in F6Publishing: 15] [Article Influence: 5.0] [Reference Citation Analysis (0)] |
10. | Kim JK, Bae H, Ko GY, Lee J, Jung J, Jekarl DW, Choi AR, Lee S, Chung BH, Yang CW, Park SC, Oh EJ. Successful ABO-incompatible living donor kidney transplantation in a recipient who developed flow cytometry crossmatch-positive donor-specific class I HLA antibodies following COVID-19 vaccination. HLA. 2022;100:52-58. [PubMed] [DOI] [Cited in This Article: ] [Reference Citation Analysis (0)] |
11. | McCune TR, Bray RA, Baran DA, Toepp AJ, Forte SJ, Gilgannon LT, Williams T, Chen S, Sadr H, Gebel HM, Herre JM. Development of donor specific antibodies after SARS-CoV-2 vaccination in kidney and heart transplant recipients. Transpl Immunol. 2022;75:101722. [PubMed] [DOI] [Cited in This Article: ] [Reference Citation Analysis (0)] |
12. | Kueht M, Kirk K, Scott Lea A, Stevenson HL, Fair J, Kathleen Gamilla-Crudo A, Hussain S, Mujtaba M. Donor-directed immunologic safety of COVID-19 vaccination in renal transplant recipients. Hum Immunol. 2022;83:607-612. [PubMed] [DOI] [Cited in This Article: ] [Cited by in F6Publishing: 2] [Reference Citation Analysis (0)] |
13. | Al Jurdi A, Gassen RB, Borges TJ, Solhjou Z, Hullekes FE, Lape IT, Efe O, Alghamdi A, Patel P, Choi JY, Mohammed MT, Bohan B, Pattanayak V, Rosales I, Cravedi P, Kotton CN, Azzi JR, Riella LV. Non-Invasive Monitoring for Rejection in Kidney Transplant Recipients After SARS-CoV-2 mRNA Vaccination. Front Immunol. 2022;13:838985. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 21] [Cited by in F6Publishing: 15] [Article Influence: 7.5] [Reference Citation Analysis (0)] |
14. | Russo G, Lai Q, Poli L, Perrone MP, Gaeta A, Rossi M, Mastroianni CM, Garofalo M, Pretagostini R. SARS-COV-2 vaccination with BNT162B2 in renal transplant patients: Risk factors for impaired response and immunological implications. Clin Transplant. 2022;36:e14495. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 43] [Cited by in F6Publishing: 31] [Article Influence: 15.5] [Reference Citation Analysis (0)] |
15. | Nishida H, Takai S, Ito H, Fukuhara H, Nawano T, Narisawa T, Kanno H, Yagi M, Yamagishi A, Sakurai T, Naito S, Tsuchiya N. Anti-human leukocyte antigen and anti-ABO antibodies after SARS-CoV-2 mRNA vaccination in kidney transplant recipients. Clin Transplant. 2023;37:e14952. [PubMed] [DOI] [Cited in This Article: ] [Reference Citation Analysis (0)] |
16. | Massa F, Cremoni M, Gérard A, Grabsi H, Rogier L, Blois M, Couzin C, Hassen NB, Rouleau M, Barbosa S, Martinuzzi E, Fayada J, Bernard G, Favre G, Hofman P, Esnault VLM, Czerkinsky C, Seitz-Polski B, Glaichenhaus N, Sicard A. Safety and cross-variant immunogenicity of a three-dose COVID-19 mRNA vaccine regimen in kidney transplant recipients. EBioMedicine. 2021;73:103679. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 35] [Cited by in F6Publishing: 59] [Article Influence: 19.7] [Reference Citation Analysis (0)] |