Role of mTOR inhibitor in the cellular and humoral immune response to a booster dose of SARS-CoV-2 mRNA-1273 vaccine in kidney transplant recipients
Copyright © 2023 Pérez-Flores, Juarez, Aiffil Meneses, Lopez-Gomez, Romero, Rodriguez-Cubillo, Moreno de la Higuera, Peix-Jiménez, Gonzalez-Garcia, Baos-Muñoz, Vilela, Gómez Del Moral, Martínez-Naves and Sanchez-Fructuoso..
Background: Immunocompromised patients have an increased risk of developing severe COVID disease, as well as a tendency to suboptimal responses to vaccines. The objective of this study was to evaluate the specific cellular and humoral adaptive immune responses of a cohort of kidney transplant recipients (KTR) after 3 doses of mRNA-1273 vaccine and to determinate the main factors involved.
Methods: Prospective observational study in 221 KTR (149 non infected), 55 healthy volunteers (HV) and 23 dialysis patients (DP). We evaluated anti-spike (by quantitative chemiluminescence immunoassay) and anti-nucleocapsid IgG (ELISA), percentage of TCD4+ and TCD8+ lymphocytes producing IFNγ against S-protein by intracellular flow cytometry after Spike-specific 15-mer peptide stimulation and serum neutralizing activity (competitive ELISA) at baseline and after vaccination.
Results: Among COVID-19 naïve KTR, 54.2% developed cellular and humoral response after the third dose (vs 100% in DP and 91.7% in HV), 18% only showed cell-mediated response, 22.2% exclusively antibody response and 5.6% none. A correlation of neutralizing activity with both the IgG titer (r=0.485, p<0.001) and the percentage of S-protein-specific IFNγ-producing CD8-T cells (r=0.198, p=0.049) was observed. Factors related to the humoral response in naïve KTR were: lymphocytes count pre-vaccination >1000/mm3 [4.68 (1.72-12.73, p=0.003], eGFR>30 mL/min [7.34(2.72-19.84), p<0.001], mTOR inhibitors [6.40 (1.37-29.86), p=0.018]. Infected KTR developed a stronger serologic response than naïve patients (96.8 vs 75.2%, p<0.001).
Conclusions: KTR presented poor cellular and humoral immune responses following vaccination with mRNA-1273. The immunosuppression degree and kidney function of these patients play an important role, but the only modifiable factor with a high impact on humoral immunogenicity after a booster dose was an immunosuppressive therapy including a mTOR inhibitor. Clinical trials are required to confirm these results.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
|---|---|
| Enthalten in: |
Frontiers in immunology - 14(2023) vom: 13., Seite 1111569 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Pérez-Flores, Isabel [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 27.02.2023 Date Revised 27.03.2023 published: Electronic-eCollection Citation Status MEDLINE |
|---|
| doi: |
10.3389/fimmu.2023.1111569 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM353237469 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM353237469 | ||
| 003 | DE-627 | ||
| 005 | 20231226210012.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3389/fimmu.2023.1111569 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1177.xml |
| 035 | |a (DE-627)NLM353237469 | ||
| 035 | |a (NLM)36817489 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Pérez-Flores, Isabel |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Role of mTOR inhibitor in the cellular and humoral immune response to a booster dose of SARS-CoV-2 mRNA-1273 vaccine in kidney transplant recipients |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 27.02.2023 | ||
| 500 | |a Date Revised 27.03.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Pérez-Flores, Juarez, Aiffil Meneses, Lopez-Gomez, Romero, Rodriguez-Cubillo, Moreno de la Higuera, Peix-Jiménez, Gonzalez-Garcia, Baos-Muñoz, Vilela, Gómez Del Moral, Martínez-Naves and Sanchez-Fructuoso. | ||
| 520 | |a Background: Immunocompromised patients have an increased risk of developing severe COVID disease, as well as a tendency to suboptimal responses to vaccines. The objective of this study was to evaluate the specific cellular and humoral adaptive immune responses of a cohort of kidney transplant recipients (KTR) after 3 doses of mRNA-1273 vaccine and to determinate the main factors involved | ||
| 520 | |a Methods: Prospective observational study in 221 KTR (149 non infected), 55 healthy volunteers (HV) and 23 dialysis patients (DP). We evaluated anti-spike (by quantitative chemiluminescence immunoassay) and anti-nucleocapsid IgG (ELISA), percentage of TCD4+ and TCD8+ lymphocytes producing IFNγ against S-protein by intracellular flow cytometry after Spike-specific 15-mer peptide stimulation and serum neutralizing activity (competitive ELISA) at baseline and after vaccination | ||
| 520 | |a Results: Among COVID-19 naïve KTR, 54.2% developed cellular and humoral response after the third dose (vs 100% in DP and 91.7% in HV), 18% only showed cell-mediated response, 22.2% exclusively antibody response and 5.6% none. A correlation of neutralizing activity with both the IgG titer (r=0.485, p<0.001) and the percentage of S-protein-specific IFNγ-producing CD8-T cells (r=0.198, p=0.049) was observed. Factors related to the humoral response in naïve KTR were: lymphocytes count pre-vaccination >1000/mm3 [4.68 (1.72-12.73, p=0.003], eGFR>30 mL/min [7.34(2.72-19.84), p<0.001], mTOR inhibitors [6.40 (1.37-29.86), p=0.018]. Infected KTR developed a stronger serologic response than naïve patients (96.8 vs 75.2%, p<0.001) | ||
| 520 | |a Conclusions: KTR presented poor cellular and humoral immune responses following vaccination with mRNA-1273. The immunosuppression degree and kidney function of these patients play an important role, but the only modifiable factor with a high impact on humoral immunogenicity after a booster dose was an immunosuppressive therapy including a mTOR inhibitor. Clinical trials are required to confirm these results | ||
| 650 | 4 | |a Observational Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a SARS-CoV-2 vaccine | |
| 650 | 4 | |a immune response | |
| 650 | 4 | |a kidney transplantation | |
| 650 | 4 | |a mTOR | |
| 650 | 7 | |a 2019-nCoV Vaccine mRNA-1273 |2 NLM | |
| 650 | 7 | |a EPK39PL4R4 |2 NLM | |
| 650 | 7 | |a MTOR Inhibitors |2 NLM | |
| 650 | 7 | |a Immunoglobulin G |2 NLM | |
| 650 | 7 | |a MTOR protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.1.1 |2 NLM | |
| 650 | 7 | |a TOR Serine-Threonine Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 700 | 1 | |a Juarez, Ignacio |e verfasserin |4 aut | |
| 700 | 1 | |a Aiffil Meneses, Arianne S |e verfasserin |4 aut | |
| 700 | 1 | |a Lopez-Gomez, Ana |e verfasserin |4 aut | |
| 700 | 1 | |a Romero, Natividad Calvo |e verfasserin |4 aut | |
| 700 | 1 | |a Rodriguez-Cubillo, Beatriz |e verfasserin |4 aut | |
| 700 | 1 | |a Moreno de la Higuera, María Angeles |e verfasserin |4 aut | |
| 700 | 1 | |a Peix-Jiménez, Belen |e verfasserin |4 aut | |
| 700 | 1 | |a Gonzalez-Garcia, Raquel |e verfasserin |4 aut | |
| 700 | 1 | |a Baos-Muñoz, Elvira |e verfasserin |4 aut | |
| 700 | 1 | |a Vilela, Ana Arribi |e verfasserin |4 aut | |
| 700 | 1 | |a Gómez Del Moral, Manuel |e verfasserin |4 aut | |
| 700 | 1 | |a Martínez-Naves, Eduardo |e verfasserin |4 aut | |
| 700 | 1 | |a Sanchez-Fructuoso, Ana Isabel |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Frontiers in immunology |d 2010 |g 14(2023) vom: 13., Seite 1111569 |w (DE-627)NLM215811453 |x 1664-3224 |7 nnns |
| 773 | 1 | 8 | |g volume:14 |g year:2023 |g day:13 |g pages:1111569 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3389/fimmu.2023.1111569 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 14 |j 2023 |b 13 |h 1111569 | ||