Humoral and Cellular Response to SARS-CoV-2 MRNA Vaccine in Paediatric Heart Transplant Recipients

Overview

Journal Heliyon

Date 2025 Jan 27

PMID 39866443

Authors

Amanda Bermejo-Gomez

Laura Tarancon-Diez

Beatriz Lazaro-Martin

Begona Santiago-Garcia

Nuria Gil Villanueva

Roberto Alonso

MA Angeles Munoz-Fernandez

Manuela Camino Lopez

Alicia Hernanz-Lobo

Maria Luisa Navarro Gomez

Affiliations

Soon will be listed here.

Abstract

Objective: The aim of this prospective cohort study is to analyse the humoral and cellular vaccine responses in paediatric heart transplant recipients (HTR, n = 12), and compare it with the response in healthy controls (HC, n = 14). All participants were 5-18 years old and vaccinated with mRNA vaccine against SARS-CoV-2 between December 2021 and May 2022.

Methods: The humoral response was measured by quantifying antibody titers against SARS-CoV-2 spike protein (anti-S). The T-lymphocyte phenotype and SARS-CoV2-specific CD4 and CD8 T-cell response was studied by multiparametric flow cytometry through peripheral blood mononuclear cells by the quantification of degranulation markers (CD107a) and intracellular cytokines (IFN-γ, TNF-α and IL-2) after stimulation with SARS-CoV-2 peptides from structural proteins (S, M, N, E) and non-structural viral proteins.

Results: After vaccination, humoral response was found in all HTR, although they showed lower levels of anti-S IgG compared to HC ( = 0.003). However, in terms of cellular response, no significant differences were obtained in the prevalence of responders and magnitude of responses between groups. In addition, anti-S IgG levels directly correlated with a higher SARS-CoV-2 specific T-cell response (rho = 0.43; = 0.027 and rho = 0.45; = 0.02 for IFN-γ and TNF-α production of CD8 T-cells, respectively). Activated T-cell phenotype in HTR was associated with a lower humoral response to SARS-CoV-2 vaccine.

Conclusion: HTR had humoral response after vaccination, although they showed lower levels of specific anti-S antibodies compared to HC. There were no significant differences in the SARS-CoV2-specific cellular response between the two groups. Obtaining satisfactory data on this type of response could potentially challenge the current vaccine guideline recommendations.

References

Picchianti-Diamanti A, Aiello A, Lagana B, Agrati C, Castilletti C, Meschi S . ImmunosuppressiveTherapies Differently Modulate Humoral- and T-Cell-Specific Responses to COVID-19 mRNA Vaccine in Rheumatoid Arthritis Patients. Front Immunol. 2021; 12:740249. PMC: 8477040. DOI: 10.3389/fimmu.2021.740249. View

Chaudhry Z, Williams J, Vahia A, Fadel R, Acosta T, Prashar R . Clinical characteristics and outcomes of COVID-19 in solid organ transplant recipients: A cohort study. Am J Transplant. 2020; 20(11):3051-3060. PMC: 7405160. DOI: 10.1111/ajt.16188. View

Deepak P, Kim W, Paley M, Yang M, Carvidi A, Demissie E . Effect of Immunosuppression on the Immunogenicity of mRNA Vaccines to SARS-CoV-2 : A Prospective Cohort Study. Ann Intern Med. 2021; 174(11):1572-1585. PMC: 8407518. DOI: 10.7326/M21-1757. View

Schmidt T, Klemis V, Schub D, Schneitler S, Reichert M, Wilkens H . 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(12):3990-4002. PMC: 8652989. DOI: 10.1111/ajt.16818. View

Van Elslande J, Oyaert M, Ailliet S, Van Ranst M, Lorent N, Vande Weygaerde Y . Longitudinal follow-up of IgG anti-nucleocapsid antibodies in SARS-CoV-2 infected patients up to eight months after infection. J Clin Virol. 2021; 136:104765. PMC: 7891078. DOI: 10.1016/j.jcv.2021.104765. View

Mbaeyi S, Oliver S, Collins J, Godfrey M, Goswami N, Hadler S . The Advisory Committee on Immunization Practices' Interim Recommendations for Additional Primary and Booster Doses of COVID-19 Vaccines - United States, 2021. MMWR Morb Mortal Wkly Rep. 2021; 70(44):1545-1552. PMC: 8568093. DOI: 10.15585/mmwr.mm7044e2. View

Fogolari M, Leoni B, De Cesaris M, Italiano R, Davini F, Miccoli G . Neutralizing Antibodies against SARS-CoV-2 Beta and Omicron Variants Inhibition Comparison after BNT162b2 mRNA Booster Doses with a New PETIA sVNT Assay. Diagnostics (Basel). 2023; 13(5). PMC: 10000738. DOI: 10.3390/diagnostics13050889. View

Klenerman P . The (gradual) rise of memory inflation. Immunol Rev. 2018; 283(1):99-112. PMC: 5947157. DOI: 10.1111/imr.12653. View

Feingold B, Berman P, Moninger A, Huston A, Stinner B, West S . Responsiveness to second and third dose of mRNA COVID-19 vaccination in adolescent and young adult heart transplant recipients. Pediatr Transplant. 2022; 26(6):e14272. PMC: 9115437. DOI: 10.1111/petr.14272. View

10.

Chambers E, Cai W, Vivaldi G, Jolliffe D, Perdek N, Li W . Influence of individuals' determinants including vaccine type on cellular and humoral responses to SARS-CoV-2 vaccination. NPJ Vaccines. 2024; 9(1):87. PMC: 11111746. DOI: 10.1038/s41541-024-00878-0. View

11.

Goss M, Galvan N, Ruan W, Munoz F, Brewer E, OMahony C . The pediatric solid organ transplant experience with COVID-19: An initial multi-center, multi-organ case series. Pediatr Transplant. 2020; 25(3):e13868. PMC: 7537006. DOI: 10.1111/petr.13868. View

12.

Boyarsky B, Werbel W, Avery R, Tobian A, Massie A, Segev D . Antibody Response to 2-Dose SARS-CoV-2 mRNA Vaccine Series in Solid Organ Transplant Recipients. JAMA. 2021; 325(21):2204-2206. PMC: 8100911. DOI: 10.1001/jama.2021.7489. View

13.

Ruether D, Schaub G, Duengelhoef P, Haag F, Brehm T, Fathi A . SARS-CoV2-specific Humoral and T-cell Immune Response After Second Vaccination in Liver Cirrhosis and Transplant Patients. Clin Gastroenterol Hepatol. 2021; 20(1):162-172.e9. PMC: 8427908. DOI: 10.1016/j.cgh.2021.09.003. View

14.

Frenck Jr R, Klein N, Kitchin N, Gurtman A, Absalon J, Lockhart S . Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents. N Engl J Med. 2021; 385(3):239-250. PMC: 8174030. DOI: 10.1056/NEJMoa2107456. View

15.

Haskin O, Ashkenazi-Hoffnung L, Ziv N, Borovitz Y, Dagan A, Levi S . Serological Response to the BNT162b2 COVID-19 mRNA Vaccine in Adolescent and Young Adult Kidney Transplant Recipients. Transplantation. 2021; 105(11):e226-e233. PMC: 8549126. DOI: 10.1097/TP.0000000000003922. View

16.

Dulek D, Ardura M, Green M, Michaels M, Chaudhuri A, Vasquez L . Update on COVID-19 vaccination in pediatric solid organ transplant recipients. Pediatr Transplant. 2022; 26(5):e14235. DOI: 10.1111/petr.14235. View

17.

Pernas M, Tarancon-Diez L, Rodriguez-Gallego E, Gomez J, G Prado J, Casado C . Factors Leading to the Loss of Natural Elite Control of HIV-1 Infection. J Virol. 2017; 92(5). PMC: 5809746. DOI: 10.1128/JVI.01805-17. View

18.

Hause A, Baggs J, Marquez P, Myers T, Gee J, Su J . COVID-19 Vaccine Safety in Children Aged 5-11 Years - United States, November 3-December 19, 2021. MMWR Morb Mortal Wkly Rep. 2021; 70(5152):1755-1760. PMC: 8736274. DOI: 10.15585/mmwr.mm705152a1. View

19.

Bahrs C, Harrison N . Vaccine Response in the Immunocompromised Patient with Focus on Cellular Immunity. Vaccines (Basel). 2022; 10(6). PMC: 9230619. DOI: 10.3390/vaccines10060882. View

20.

Vafadari R, Kraaijeveld R, Weimar W, Baan C . Tacrolimus inhibits NF-κB activation in peripheral human T cells. PLoS One. 2013; 8(4):e60784. PMC: 3613409. DOI: 10.1371/journal.pone.0060784. View