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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

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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 5

An impaired DC homing and functional capacity are associated with a lower T cell response to the SARS-CoV-2 vaccine in aged people.

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An impaired DC homing and functional capacity are associated with a lowe...
(A) Dot plots showing IFN-α production through CpG-A stimulation for 18 hours 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) (left). Correlation analysis of IFN-α production with anti–RBD IgG levels 3 weeks after the first dose of vaccination (right). (B and C) Bar graphs representing the percentage of CD1c+ and IDO+CD1c+ mDCs in > 60-year-old (red) and < 60-year-old (blue) participants at the 3 follow-up time points. (D) Correlation matrix showing associations between the percentages of CD1c+ mDCs and IDO+CD1c+ mDCs before vaccination with SARS-CoV-2 S–specific T cells expressing cytokines or cytotoxicity markers 2 months after the second dose. (E–G) Dot plots showing the percentage of CD1c+ mDCs expressing CD86 (E), PD-L1 (F), and CD4 (G) in > 60-year-old (red) and < 60-year-old (blue) participants at the 3 time points. (H) Dot plots showing the percentage of CD141+ mDCs expressing CD86 (left) in > 60-year-old (red) and < 60-year-old (blue) participants at the 3 time points. Correlation plot between the percentage of CD86+CD141+ mDCs before vaccination and the percentage of S-specific PRF+ TEMRA CD4+ and CD8+ T cells 2 months after the second dose (right). (I) Correlation matrix showing associations between the percentage of CD141+ mDCs expressing activation markers after TLR-3 stimulation for 24 hours with SARS-CoV-2 S–specific CD4+ and CD8+ T cells expressing cytotoxicity markers. (J) Dot plots showing the percentage of CCR7+ mDCs in > 60-year-old (red) and < 60-year-old (blue) participants in the 3 follow-up time points (left and middle panels), and a correlation matrix representing associations of the percentage of mDCs expressing CCR7 with SARS-CoV-2 S–specific CD4+ and CD8+ T cells expressing cytokines or cytotoxicity markers 2 months after the second dose (right panel). Mann-Whitney U (A, B, C, E, F, G, H, and J), Wilcoxon (A, B, C, E, F, G, H, and J), and Spearman (A, D, H, I, and J) tests were used (n = 32). Friedman test was applied in A (> 60-year-old, P = 0.801; < 60-year-old, P = 0.717), B (> 60-year-old, P = 0.169; < 60-year-old, P = <0.0001), C (> 60-year-old, P = 0.147; < 60-year-old, P = 0.027), E (> 60-year-old, P = 0.018; < 60-year-old, P = 0.086), F (> 60-year-old, P = 0.381; < 60-year-old, P = 0.013), G (> 60-year-old, P = 0.042; < 60-year-old, P = 0.034), H (> 60-year-old, P = 0.223; < 60-year-old, P = 0.234), and J (CD1c mDCs: > 60-year-old, P = 0.121; < 60-year-old, P = 0.001 and CD141 mDCs: > 60-year-old, P = 0.459; < 60-year-old, P = 0.001).

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