Immune defects associated with lower SARS-CoV-2 BNT162b2 mRNA vaccine response in aged people
Joana Vitallé, … , Mohammed Rafii-El-Idrissi Benhnia, Ezequiel Ruiz-Mateos
Joana Vitallé, … , Mohammed Rafii-El-Idrissi Benhnia, Ezequiel Ruiz-Mateos
Published August 9, 2022
Citation Information: JCI Insight. 2022;7(17):e161045. https://doi.org/10.1172/jci.insight.161045.
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Research Article Immunology Vaccines

Immune defects associated with lower SARS-CoV-2 BNT162b2 mRNA vaccine response in aged people

Abstract

The immune factors associated with impaired SARS-CoV-2 vaccine response in elderly people are mostly unknown. We studied individuals older than 60 and younger than 60 years, who had been vaccinated with SARS-CoV-2 BNT162b2 mRNA, before and after the first and second dose. Aging was associated with a lower anti–RBD IgG levels and a decreased magnitude and polyfunctionality of SARS-CoV-2–specific T cell response. The dramatic decrease in thymic function in people > 60 years, which fueled alteration in T cell homeostasis, and their lower CD161+ T cell levels were associated with decreased T cell response 2 months after vaccination. Additionally, deficient DC homing, activation, and TLR-mediated function, along with a proinflammatory functional profile in monocytes, were observed in the > 60-year-old group, which was also related to lower specific T cell response after vaccination. These findings might be relevant for the improvement of the current vaccination strategies and for the development of new vaccine prototypes.

Authors

Joana Vitallé, Alberto Pérez-Gómez, Francisco José Ostos, Carmen Gasca-Capote, María Reyes Jiménez-León, Sara Bachiller, Inmaculada Rivas-Jeremías, Maria del Mar Silva-Sánchez, Anabel M. Ruiz-Mateos, María Ángeles Martín-Sánchez, Luis Fernando López-Cortes, Mohammed Rafii-El-Idrissi Benhnia, Ezequiel Ruiz-Mateos

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Figure 3

Lower thymic function and altered T cell homeostasis found in aged people are associated with a lower T cell response to the SARS-CoV-2 vaccine.

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Lower thymic function and altered T cell homeostasis found in aged peopl...
(A and B) Bar graphs showing TREC/1 × 106 cells as a measure of thymic function in > 60-year-old and < 60-year-old participants prior to vaccination (A, left) and the correlation of the TREC/1 × 106 cells with age (A, right), naive CD4+ T cells (B, left), naive CD8+ T cells (B, middle), and naive CD4+/CD8+ T cell ratio (B, right). (C) Bar graphs representing the percentage of naive and memory CD4+ and CD8+ T cells in > 60-year-old (red) and < 60-year-old (blue) participants before SARS-CoV-2 vaccination (PRE), 3 weeks after the first dose (1D), and 2 months after the second dose (2D). (D and E) Dot plots representing the percentage of memory and CM CD4+ T cells expressing HLA-DR (D) and Ki67 (E) > 60-year-old (red) and < 60-year-old (blue) participants at the 3 time points (right). Pseudocolor dot plot graphs show representative data of memory CD4+ T cells from a > 60-year-old (red) and < 60-year-old (blue) donor expressing HLA-DR (D) and Ki67 (E) before vaccination (left). (F and G) Correlation matrixes representing associations of SARS-CoV-2 S–specific CD4+ and CD8+ T cells expressing IFN-γ or cytotoxicity markers 2 months after the second dose of vaccination with TREC/1 × 106 cells and naive T cells (F) and with the percentage of HLA-DR+ and Ki67+ CD4+ T cells (G) before vaccination in all participants. (H) Correlation plots of anti–RBD IgG levels after the first dose of vaccination with the percentage of HLA-DR+ and Ki67+ CD4+ T cells before vaccination. (I) Bar graphs representing the percentage of SARS-CoV-2–specific CD4+ T cells expressing LAG-3 in > 60-year-old (red) and < 60-year-old (blue) participants at the 3 follow-up time points. Mann-Whitney U (A, C, D, E, and I), Wilcoxon (A, C, D, E, and I), and Spearman (A, B, F, G, and H) tests were used (n = 32). Friedman test was applied in C (Naive CD4+ T cells: > 60-year-old, P = 0.06, and < 60-year-old, P = 0.074; Memory CD4+ T cells: > 60-year-old, P = 0.071, and < 60-year-old, P = 0.074; Naive CD8+ T cells: > 60-year-old, P = 0.307, and < 60-year-old, P = 0.015; Memory CD8+ T cells: > 60-year-old, P = 0.035, and < 60-year-old, P = 0.091), D (Memory CD4+ T cells: > 60-year-old, P = 0.441, and < 60-year-old, P = 0.022; CM CD4+ T cells: > 60-year-old, P = 0.529, and < 60-year-old, P = 0.022), and E (Memory CD4+ T cells: > 60-year-old, P = 0.273, and < 60-year-old, P = 0.074; CM CD4+ T cells: > 60-year-old, P = 0.657, and < 60-year-old, P = 0.091). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.