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Article

Immunosuppressive Therapy Modifies Anti-Spike IgG Subclasses Distribution After Four Doses of mRNA Vaccination in a Cohort of Kidney Transplant Recipients

by
Ignacio Juarez
1,*,†,
Isabel Pérez-Flores
2,†,
Arianne S. Aiffil Meneses
2,
Ana Lopez-Gomez
1,
Natividad Calvo Romero
2,
Beatriz Rodríguez-Cubillo
2,
María Angeles Moreno de la Higuera
2,
Belén Peix-Jiménez
2,
Raquel Gonzalez-Garcia
1,
Beatriz Amorós-Pérez
1,
Benigno Rivas-Pardo
1,
Elvira Baos-Muñoz
3,
Ana Arribi Vilela
3,
Manuel Gómez Del Moral
4,
Ana Isabel Sánchez-Fructuoso
2,‡ and
Eduardo Martínez-Naves
1,‡
1
Immunology Department, Complutense University of Madrid, 28040 Madrid, Spain
2
Nephrology Department, Institute San Carlos for Medical Research (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC)), San Carlos Clinical University Hospital, 28040 Madrid, Spain
3
Microbiology Department, Institute San Carlos for Medical Research (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC)), San Carlos Clinical University Hospital, 28040 Madrid, Spain
4
Department of Cell Biology, Complutense University of Madrid, 28040 Madrid, Spain
*
Author to whom correspondence should be addressed.
I.P.-F. and I.J. share co-first authorship.
E.M.-N. and A.I.S.-F. share co-senior authorship.
Vaccines 2025, 13(2), 123; https://doi.org/10.3390/vaccines13020123
Submission received: 16 December 2024 / Revised: 20 January 2025 / Accepted: 22 January 2025 / Published: 25 January 2025
(This article belongs to the Special Issue Immunization of Immunosuppressed Patients)

Abstract

Background: IgG4 is the least immunogenic subclass of IgG. Immunization with mRNA vaccines against SARS-CoV-2, unlike other vaccines, induces an increase in IgG4 against the spike protein in healthy populations. This study investigated whether immunosuppressive therapy affects the immune response, focusing on IgG subclass changes, to four doses of mRNA vaccine in kidney transplant recipients (KTRs). Methods: This study includes 146 KTRs and 23 dialysis patients (DPs) who received three mRNA-1273 vaccine doses and a BNT162b2 booster. We evaluated anti-spike IgG titers and subclasses, T-CD4+ and T-CD8+ cellular responses, and serum neutralizing activity (SNA). Results: At the fourth dose, 75.8% of COVID-19 naïve KTRs developed humoral and cellular responses (vs. 95.7% in DPs). There was a correlation between anti-spike IgG titers/subclasses and SNA (p < 0.001). IgG subclass kinetics after the third/fourth dose differed between COVID-19 naïve KTRs and DPs. Immunosuppressive therapy influenced IgG subclasses: mTOR inhibitors (mTORi) positively influenced IgG1 and IgG3 (p < 0.05), while mycophenolic acid negatively affected IgG1, IgG3, and IgG4 (p < 0.05). SNA is correlated with breakthrough infections after four doses of vaccine in KTRs. mTORi was the only factor associated with SNA > 65% in naïve KTRs [4.29 (1.21–15.17), p = 0.024]. Conclusions: KTRs show weaker cellular and humoral immune responses to mRNA vaccines and a class shift towards non-inflammatory anti-S IgG4 upon booster doses. IgG subclasses show a positive correlation with SNA and are influenced by immunosuppression. Increased SNA after four doses of vaccine is protective against infection. mTORi may benefit non-responding KTRs.
Keywords: kidney transplant recipients; SARS-CoV-2 vaccine; serum neutralizing activity; IgG subclasses; COVID-19 kidney transplant recipients; SARS-CoV-2 vaccine; serum neutralizing activity; IgG subclasses; COVID-19

Share and Cite

MDPI and ACS Style

Juarez, I.; Pérez-Flores, I.; Aiffil Meneses, A.S.; Lopez-Gomez, A.; Calvo Romero, N.; Rodríguez-Cubillo, B.; Moreno de la Higuera, M.A.; Peix-Jiménez, B.; Gonzalez-Garcia, R.; Amorós-Pérez, B.; et al. Immunosuppressive Therapy Modifies Anti-Spike IgG Subclasses Distribution After Four Doses of mRNA Vaccination in a Cohort of Kidney Transplant Recipients. Vaccines 2025, 13, 123. https://doi.org/10.3390/vaccines13020123

AMA Style

Juarez I, Pérez-Flores I, Aiffil Meneses AS, Lopez-Gomez A, Calvo Romero N, Rodríguez-Cubillo B, Moreno de la Higuera MA, Peix-Jiménez B, Gonzalez-Garcia R, Amorós-Pérez B, et al. Immunosuppressive Therapy Modifies Anti-Spike IgG Subclasses Distribution After Four Doses of mRNA Vaccination in a Cohort of Kidney Transplant Recipients. Vaccines. 2025; 13(2):123. https://doi.org/10.3390/vaccines13020123

Chicago/Turabian Style

Juarez, Ignacio, Isabel Pérez-Flores, Arianne S. Aiffil Meneses, Ana Lopez-Gomez, Natividad Calvo Romero, Beatriz Rodríguez-Cubillo, María Angeles Moreno de la Higuera, Belén Peix-Jiménez, Raquel Gonzalez-Garcia, Beatriz Amorós-Pérez, and et al. 2025. "Immunosuppressive Therapy Modifies Anti-Spike IgG Subclasses Distribution After Four Doses of mRNA Vaccination in a Cohort of Kidney Transplant Recipients" Vaccines 13, no. 2: 123. https://doi.org/10.3390/vaccines13020123

APA Style

Juarez, I., Pérez-Flores, I., Aiffil Meneses, A. S., Lopez-Gomez, A., Calvo Romero, N., Rodríguez-Cubillo, B., Moreno de la Higuera, M. A., Peix-Jiménez, B., Gonzalez-Garcia, R., Amorós-Pérez, B., Rivas-Pardo, B., Baos-Muñoz, E., Arribi Vilela, A., Gómez Del Moral, M., Sánchez-Fructuoso, A. I., & Martínez-Naves, E. (2025). Immunosuppressive Therapy Modifies Anti-Spike IgG Subclasses Distribution After Four Doses of mRNA Vaccination in a Cohort of Kidney Transplant Recipients. Vaccines, 13(2), 123. https://doi.org/10.3390/vaccines13020123

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