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 7

Diminished monocyte activation and homing found in aged people are related to a lower SARS-CoV-2 vaccine response.

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Diminished monocyte activation and homing found in aged people are relat...
(A) Dot plots representing the percentage of classical monocytes expressing CD40 (top) and TLR-4 (bottom) 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) of vaccination (left). A correlation matrix representing the percentage of monocytes expressing CD40 and TLR-4 prior to vaccination with SARS-CoV-2 S–specific CD4+ and CD8+ T cells expressing cytokines or cytotoxicity markers 2 months after the second dose (right). (B and C) Dot plots representing the percentage of classical monocytes expressing CCR5 before vaccination (B, left), the fold of decrease in the percentage of CCR5+ cells after the first dose (B, right), and correlation analysis of the percentage of CCR5+ classical monocytes prior to vaccination with SARS-CoV-2 S–specific CD4+ and CD8+ T cells expressing IFN-γ 2 months after the second dose (C). (D and E) Dot plots showing the percentages of nonclassical monocytes expressing CX3CR1 in > 60-year-old (red) and < 60-year-old (blue) participants at the 3 follow-up time points (D). Correlations of the percentage of nonclassical monocytes expressing CX3CR1 2 months after the second dose (E, left) and prior vaccination (E, right) with SARS-CoV-2 S–specific IFN-γ+ CD4+ T cells after the second dose. (F and G) Dot plots showing the percentages of monocytes expressing CD11b in > 60-year-old (red) and < 60-year-old (blue) participants at the 3 follow-up time points (F). Correlation plots between the percentage of CD11b+ classical monocytes with SARS-CoV-2 S–specific IFN-γ+ CD4+ T cells (G, left) and anti–RBD IgG levels (G, right) 2 months after the second dose. Mann-Whitney U (A, B, D, and F), Wilcoxon (A, B, D, and F), and Spearman (A, C, E, and G) tests were used (n = 28). Friedman test was applied in A (CD40: > 60-year-old, P = 0.006, and < 60-year-old, P = 0.050; TLR4: > 60-year-old, P = 0.042, and < 60-year-old, P = 0.779), D (> 60-year-old, P = 0.002; < 60-year-old, P = 0.717) and F (> 60-year-old, P = 0.607; < 60-year-old, P = 0.368).