First report of antibody response to SARS-CoV-2 mRNA vaccine in kidney transplant recipients

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease (COVID-19), which was declared a pandemic in March 2020, has since caused a serious global health crisis. COVID-19 has spread to more than 200 countries and millions have fallen ill. Patients who...

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Published inJapanese Journal of Transplantation Vol. 57; no. 2; pp. 141 - 151
Main Authors UNAGAMI, Kouhei, ISHIDA, Hideki, TAKAGI, Toshio, OMOTO, Kazuya, TANABE, Kazunari, FURUSAWA, Miyuki, YAGISAWA, Takafumi, ISHII, Kota, KANZAWA, Taichi, IIZUKA, Junpei
Format Journal Article
LanguageJapanese
Published The Japan Society for Transplantation 2022
一般社団法人 日本移植学会
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Online AccessGet full text
ISSN0578-7947
2188-0034
DOI10.11386/jst.57.2_141

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Abstract Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease (COVID-19), which was declared a pandemic in March 2020, has since caused a serious global health crisis. COVID-19 has spread to more than 200 countries and millions have fallen ill. Patients who have undergone an organ transplant are at increased risk of complications from COVID-19 due to conditions such as hypertension, diabetes, cardiovascular disease, chronic lung disease, and obesity, as well as chronic immunosuppression. We measured antibodies to the five SARS-CoV-2 proteins in kidney transplant patients who received two approved and available BNT162B2 (mRNA) vaccinations. It is possible to simultaneously identify antibody reactions to the extracellular domain (ECD), the three individual domains of the spike protein (S1, S2, and the receptor-binding domain (RBD)), and the five proteins of the nucleocapsid. The serological response following BNT162B2 COVID-19 mRNA vaccination was investigated using possible receptors. The subjects were 111 patients one month after receiving two coronavirus vaccines following kidney transplantation. Antibodies were found in 41% (46 cases). The positive rate of antibody formation tended to be low in transplant patients, whereas in the control group of healthy subjects it was 100%. The positive rate indicated by immunosuppressant was 36% (37/100) in the cases using tacrolimus at the time of vaccination and 90% (9/10) in the cases using cyclosporine. The intensity of each fragment in antibody-positive cases showed the normalized mean fluorescence intensity (nMFI), which indicated the highest ECD levels in the transplant patients and healthy control groups, followed by RBD, S1, and S2. In the reactivity pattern of the fragments of the positive cases, the control group had an nMFI of 110,000 to 140,000, while the transplant patients had an nMFI of 6,900 to 25,000, showing a difference in cumulative nMFI. The proportion of fragments also varied greatly among transplant patients, and no uniformity was observed. By contrast, in the healthy control group, the nMFI value tended to be constant for each fragment. The results suggest that performing antibody monitoring during the Coronavirus crisis may be useful for the protection against and treatment of infection as well as in determining the individual vaccination interval, vaccination amount, and number of vaccinations required.
AbstractList Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease (COVID-19), which was declared a pandemic in March 2020, has since caused a serious global health crisis. COVID-19 has spread to more than 200 countries and millions have fallen ill. Patients who have undergone an organ transplant are at increased risk of complications from COVID-19 due to conditions such as hypertension, diabetes, cardiovascular disease, chronic lung disease, and obesity, as well as chronic immunosuppression. We measured antibodies to the five SARS-CoV-2 proteins in kidney transplant patients who received two approved and available BNT162B2 (mRNA) vaccinations. It is possible to simultaneously identify antibody reactions to the extracellular domain (ECD), the three individual domains of the spike protein (S1, S2, and the receptor-binding domain (RBD)), and the five proteins of the nucleocapsid. The serological response following BNT162B2 COVID-19 mRNA vaccination was investigated using possible receptors. The subjects were 111 patients one month after receiving two coronavirus vaccines following kidney transplantation. Antibodies were found in 41% (46 cases). The positive rate of antibody formation tended to be low in transplant patients, whereas in the control group of healthy subjects it was 100%. The positive rate indicated by immunosuppressant was 36% (37/100) in the cases using tacrolimus at the time of vaccination and 90% (9/10) in the cases using cyclosporine. The intensity of each fragment in antibody-positive cases showed the normalized mean fluorescence intensity (nMFI), which indicated the highest ECD levels in the transplant patients and healthy control groups, followed by RBD, S1, and S2. In the reactivity pattern of the fragments of the positive cases, the control group had an nMFI of 110,000 to 140,000, while the transplant patients had an nMFI of 6,900 to 25,000, showing a difference in cumulative nMFI. The proportion of fragments also varied greatly among transplant patients, and no uniformity was observed. By contrast, in the healthy control group, the nMFI value tended to be constant for each fragment. The results suggest that performing antibody monitoring during the Coronavirus crisis may be useful for the protection against and treatment of infection as well as in determining the individual vaccination interval, vaccination amount, and number of vaccinations required.
Author UNAGAMI, Kouhei
YAGISAWA, Takafumi
TAKAGI, Toshio
TANABE, Kazunari
OMOTO, Kazuya
ISHIDA, Hideki
KANZAWA, Taichi
FURUSAWA, Miyuki
ISHII, Kota
IIZUKA, Junpei
Author_FL FURUSAWA Miyuki
飯塚 淳平
高木 敏男
海上 耕平
ISHIDA Hideki
ISHII Kota
田邉 一成
尾本 和也
八木澤 隆史
KANZAWA Taichi
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References 20) Furer V, Eviatar T, Zisman D, et al. Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in adult patients with autoimmune inflammatory rheumatic diseases and in the general population: a multicentre study. Ann Rheum Dis 2021; 80 (10) : 1330-1338.
10) Glenn DA, Hegde A, Kotzen E, et al. Systematic review of safety and efficacy of COVID-19 vaccines in patients with kidney disease. Kidney Int Rep 2021; 6: 1407-1410.
3) Jin X, Lian JS, Hu JH. Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms. Gut 2020; 69 (6) : 1002-1009.
14) Bray RA, Lee J-H, Brescia P, et al. Development and validation of a multiplex, bead-based assay to detect antibodies directed against SARS-CoV-2 proteins. Transplantation 2021; 105 (1) : 79-89.
1) ERACODA Working Group. Chronic kidney disease is a key risk factor for severe COVID-19: a call to action by the ERA-EDTAERA-EDTA Council. Nephrol Dial Transplant 2021; 36 (1) : 87-94.
4) Tian Y, Rong L, Nian W, et al. Review article: gastrointestinal features in COVID-19 and the possibility of faecal transmission. Aliment Pharmacol Ther 2020; 51 (9) : 843-851.
22) Kamar N, Abravanel F, Marion O, et al. Three doses of an mRNA Covid-19 vaccine in solid-organ transplant recipients. N Engl J Med 2021; 385 (7) : 661-662.
11) Kageyama T, Ikeda K, Tanaka S, et al. Antibody responses to BNT162b2 mRNA COVID-19 vaccine in 2,015 healthcare workers in a single tertiary referral hospital in Japan. medRxiv 2021.
5) Oxley TJ, Mocco J, Majidi S. Large-vessel stroke as a presenting feature of Covid-19 in the young. N Engl J Med 2020; 382 (20) : 1002-1009.
12) Rincon-Arevalo H, Choi M, Stefanski A-L, et al. Impaired humoral immunity to SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients and dialysis patients. Sci Immunol 2021; 6 (60) : 1-13.
13) Ng KW, Faulkner N, Cornish GH, et al. Preexisting and de novohumoral immunity to SARS-CoV-2 in humans. Science 2020; 370 (6522) : 1339-1343.
16) Wrapp D, Wang N, Corbett KS, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 2020; 367: 1260-1263.
25) Grupper A, Rabinowich L, Schwartz D, et al. Reduced humoral response to mRNA SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients without prior exposure to the virus. Am J Transplant 2021; 21 (8) : 2719-2726.
17) Walls AC, Park Y-J, Tortorici MA, et al. Structure, function, and antigenicity of the SARS-CoV-2 Spike glycoprotein. Cell 2020; 181: 281-292.
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18) Graham C, Seow J, Huettner I, et al. Neutralization potency of monoclonal antibodies recognizing dominant and subdominant epitopes on SARS-CoV-2 Spike is impacted by the B.1.1.7 variant. Immunity 2021; 54 (6) : 1276-1289.
23) 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.
9) Kamar N, Abravanel F, Marion O, et al. Three doses of an mRNA Covid-19 vaccine in solid-organ transplant recipients. N Engl J Med 2021; 385 (7) : 661-662.
19) Weisberg SP, Connors T, Zhu Y, et al. Distinct antibody responses to SArSA-CoV-2 in children and adults across the COVID-19 clinical spectrum. Nat Immunol 2021; 22 (1) : 25-31.
24) Benotmane I, Gautier-Vargas G, Cognard N, et al. Low immunization rates among kidney transplant recipients who received 2 doses of the mRNA-1273 SARS-CoV-2 vaccine. Kidney Int 2021; 99: 1498-1500.
15) Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; 181: 271-280.
26) Okba NMA, Raj VS, Widjaja I, et al. Sensitive and specific detection of low-level antibody responses in mild Middle East respiratory syndrome coronavirus infections. Emerg Infect Dis 2019; 25: 1868-1877.
8) Azzi Y, Bartash R, Scalea J, et al. COVID-19 and solid organ transplantation: a review article. Transplantation 2021; 105 (1) : 37-55.
21) Eisenberg RA, Jawad AF, Boyer J, et al. Rituximab-treated patients have a poor response to influenza vaccination. J Clin Immunol 2013; 33: 388-396.
References_xml – reference: 5) Oxley TJ, Mocco J, Majidi S. Large-vessel stroke as a presenting feature of Covid-19 in the young. N Engl J Med 2020; 382 (20) : 1002-1009.
– reference: 20) Furer V, Eviatar T, Zisman D, et al. Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in adult patients with autoimmune inflammatory rheumatic diseases and in the general population: a multicentre study. Ann Rheum Dis 2021; 80 (10) : 1330-1338.
– reference: 4) Tian Y, Rong L, Nian W, et al. Review article: gastrointestinal features in COVID-19 and the possibility of faecal transmission. Aliment Pharmacol Ther 2020; 51 (9) : 843-851.
– reference: 1) ERACODA Working Group. Chronic kidney disease is a key risk factor for severe COVID-19: a call to action by the ERA-EDTAERA-EDTA Council. Nephrol Dial Transplant 2021; 36 (1) : 87-94.
– reference: 21) Eisenberg RA, Jawad AF, Boyer J, et al. Rituximab-treated patients have a poor response to influenza vaccination. J Clin Immunol 2013; 33: 388-396.
– reference: 12) Rincon-Arevalo H, Choi M, Stefanski A-L, et al. Impaired humoral immunity to SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients and dialysis patients. Sci Immunol 2021; 6 (60) : 1-13.
– reference: 2) Zhang C, Shi L, Wang FS. Liver injury in COVID-19: management and challenges. Lancet Gastroenterol Hepatol 2020; 5 (5) : 428-430.
– reference: 6) Ye M, Ren Y, Lv T. Encephalitis as a clinical manifestation of COVID-19. Brain Behav Immun 2020; 88: 945-946.
– reference: 19) Weisberg SP, Connors T, Zhu Y, et al. Distinct antibody responses to SArSA-CoV-2 in children and adults across the COVID-19 clinical spectrum. Nat Immunol 2021; 22 (1) : 25-31.
– reference: 3) Jin X, Lian JS, Hu JH. Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms. Gut 2020; 69 (6) : 1002-1009.
– reference: 16) Wrapp D, Wang N, Corbett KS, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 2020; 367: 1260-1263.
– reference: 23) 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.
– reference: 7) Bikdeli B, Madhavan MV, Jimenez D. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up. J Am Coll Cardiol 2020; 75 (23) : 2950-2973.
– reference: 15) Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; 181: 271-280.
– reference: 17) Walls AC, Park Y-J, Tortorici MA, et al. Structure, function, and antigenicity of the SARS-CoV-2 Spike glycoprotein. Cell 2020; 181: 281-292.
– reference: 26) Okba NMA, Raj VS, Widjaja I, et al. Sensitive and specific detection of low-level antibody responses in mild Middle East respiratory syndrome coronavirus infections. Emerg Infect Dis 2019; 25: 1868-1877.
– reference: 11) Kageyama T, Ikeda K, Tanaka S, et al. Antibody responses to BNT162b2 mRNA COVID-19 vaccine in 2,015 healthcare workers in a single tertiary referral hospital in Japan. medRxiv 2021.
– reference: 10) Glenn DA, Hegde A, Kotzen E, et al. Systematic review of safety and efficacy of COVID-19 vaccines in patients with kidney disease. Kidney Int Rep 2021; 6: 1407-1410.
– reference: 25) Grupper A, Rabinowich L, Schwartz D, et al. Reduced humoral response to mRNA SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients without prior exposure to the virus. Am J Transplant 2021; 21 (8) : 2719-2726.
– reference: 14) Bray RA, Lee J-H, Brescia P, et al. Development and validation of a multiplex, bead-based assay to detect antibodies directed against SARS-CoV-2 proteins. Transplantation 2021; 105 (1) : 79-89.
– reference: 13) Ng KW, Faulkner N, Cornish GH, et al. Preexisting and de novohumoral immunity to SARS-CoV-2 in humans. Science 2020; 370 (6522) : 1339-1343.
– reference: 18) Graham C, Seow J, Huettner I, et al. Neutralization potency of monoclonal antibodies recognizing dominant and subdominant epitopes on SARS-CoV-2 Spike is impacted by the B.1.1.7 variant. Immunity 2021; 54 (6) : 1276-1289.
– reference: 27) 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 (7) : 1205-1211.
– reference: 8) Azzi Y, Bartash R, Scalea J, et al. COVID-19 and solid organ transplantation: a review article. Transplantation 2021; 105 (1) : 37-55.
– reference: 22) Kamar N, Abravanel F, Marion O, et al. Three doses of an mRNA Covid-19 vaccine in solid-organ transplant recipients. N Engl J Med 2021; 385 (7) : 661-662.
– reference: 9) Kamar N, Abravanel F, Marion O, et al. Three doses of an mRNA Covid-19 vaccine in solid-organ transplant recipients. N Engl J Med 2021; 385 (7) : 661-662.
– reference: 24) Benotmane I, Gautier-Vargas G, Cognard N, et al. Low immunization rates among kidney transplant recipients who received 2 doses of the mRNA-1273 SARS-CoV-2 vaccine. Kidney Int 2021; 99: 1498-1500.
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Snippet Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease (COVID-19), which was declared a pandemic in March...
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SubjectTerms antibody titer
COVID-19
renal transplantation
SARS-CoV-2
vaccination
Title First report of antibody response to SARS-CoV-2 mRNA vaccine in kidney transplant recipients
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