Humoral and cellular response to SARS-CoV-2 mRNA vaccine in paediatric heart transplant recipients

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 in vitro 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 (p = 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; p = 0.027 and rho = 0.45; p = 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.

Keywords: COVID-19; Cell-mediated immunity; Heart transplant recipients; Humoral immunity; Immunocompromised; Paediatric; SARS-CoV-2; Vaccines.

Graphical abstract

Fig. 1

Humoral and cellular specific SARS-CoV-2 response after vaccination. Bar graphs representing anti-S IgG levels after vaccination in paediatric and adolescent heart transplant recipients (red; n = 12) and healthy controls (green; n = 14) (A). Dot plots representing the percentage of SARS-CoV-2 specific T-cell response (left) and rate of responders (right) within total and memory (CD45RA⁻) CD4⁺ and CD8⁺ T-cell comparing heart transplant recipients and healthy controls after vaccination (B). Bar graphs representing anti-S IgG levels after vaccination in paediatric and adolescent participants with previous SARS-CoV-2 infection (purple; n = 16) and without previous infection (orange; n = 10) (C). Dot plots representing the percentage of SARS-CoV-2 specific T-cell response (left) and rate of responders (right) within total and memory (CD45RA⁻) CD4⁺ and CD8⁺ T-cell comparing participants with previous SARS-CoV-2 infection and without previous infection (D). For C and D HTR and HC have been represented by squares and triangles, respectively. Abbreviation: HTR, heart transplant recipients; HC, healthy controls. Continuous variables were compared using Mann-Whitney U test and rate of responders using X² test. #0.05≤p-value<0.1; ∗p-value<0.05; ∗∗p-value<0.01. Only statistical p-value <0.1 is shown.

Fig. 2

Association of SARS-CoV-2–specific anti-S IgG levels with T-cell response after vaccination. Correlation matrix presenting associations of anti-IgG levels with SARS-CoV-2-specific total and CD45RA⁻ CD4⁺ and CD8⁺ T-cells expressing CD107a⁺ and producing the cytokines IFN-γ⁺, TNF-α⁺ and IL-2⁺ in all paediatric and adolescent participants (n = 26), heart transplant recipients (n = 12) and healthy controls (n = 14) (A). Dots plots representing correlations between anti-IgG levels and SARS-CoV-2-specific CD8⁺ T-cells producing IFN-γ⁺ (B) and TNF-α⁺ (C) in all participants. Abbreviations: HTR, heart transplant recipients; HC, healthy controls. The Spearman rho correlation coefficient test was used. #0.05≤p-value<0.1; ∗p-value<0.05; ∗∗p-value<0.01.

Fig. 3

Association of SARS-CoV-2–specific anti-S IgG levels and SARS-CoV-2-specific T-cell degranulation with phenotype expression markers on T-cells after vaccination. Dot plots representing correlations between anti-IgG levels and CD25⁺ expression on total CD4⁺ T-cells (A) and HLA-DR⁺CD38⁺ co-expression on CD45RA⁻ CD4⁺ T-cells (B). Dot plots representing correlation between SARS-CoV-2 specific degranulation marker CD107a⁺ on CD45RA⁻ CD4⁺ T-cells and CD25⁺ expression on CD45RA⁻ CD4⁺ T-cells (C) (n = 26). Correlations remained after excluding the outlier value (∗in blue) in each case (A–B). Heart transplant recipients are indicated in red and healthy controls in green. The Spearman rho correlation coefficient test was used.