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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 2

Aged people show a lower and less polyfunctional SARS-CoV-2 S–specific CD4+ and CD8+ T cell response after the vaccination.

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Aged people show a lower and less polyfunctional SARS-CoV-2 S–specific C...
(A and B) Dot plots presenting the percentage of IFN-γ+, CD107a+, and PRF+ cells within memory, CM, EM, and TEMRA CD4+ (A) and CD8+ (B) T cells after S-specific SARS-CoV-2 stimulation, comparing participants > 60 years old (red) and < 60 years old (blue) 3 weeks after the first dose (1D) and 2 months after the second dose (2D) of SARS-CoV-2 vaccine (right). Pseudocolor dot plot graphs show a representative data of memory CD4+ T cells from a > 60-year-old and a < 60-year-old donor 2 months after vaccination (left). (C) Pie charts representing SARS-CoV-2 S–specific memory CD4+ T cell polyfunctionality. Each sector represents the proportion of S-specific CD4+ T cells producing 2 (green) or 1 (blue) functions. Arcs represent the type of function (CD107a, IFN-γ, IL-2, PRF, and TNF-α) expressed in each sector. (D) Bar graphs showing the percentage of EM and CM CD4+ T cells expressing different combinations of studied functions (CD107a, IFN-γ, IL-2, PRF, and TNF-α) comparing > 60-year-old (red) and < 60-year-old (blue) participants after the first (1D) and the second (2D) dose. Mann-Whitney U (A, B, and D), Wilcoxon (A, B, and D), and Permutation (C) tests were used (n = 41). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.

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