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Overcoming the age-dependent SARS-CoV-2 vaccine response through hybrid immunity: analysis of humoral and cellular immunity with mass cytometry profiling

Authors
 Zayakhuu Gerelkhuu  ;  Sehee Park  ;  Kyoung Hwa Lee  ;  Yong Chan Kim  ;  Sook Jin Kwon  ;  Kyoung-Ho Song  ;  Eu Suk Kim  ;  Young Goo Song  ;  Yoon Soo Park  ;  Jin Young Ahn  ;  Jun Yong Choi  ;  Won Suk Choi  ;  Seongman Bae  ;  Sung-Han Kim  ;  Shin-Woo Kim  ;  Ki Tae Kwon  ;  Hye Won Jeong  ;  Kyong Ran Peck  ;  Eun-Suk Kang  ;  June-Young Koh  ;  Jae-Hoon Ko  ;  Tae Hyun Yoon 
Citation
 IMMUNITY & AGEING, Vol.21(1) : 51, 2024-07 
Journal Title
IMMUNITY & AGEING
Issue Date
2024-07
Keywords
Aging ; COVID-19 vaccines ; Immunity ; Mass cytometry
Abstract
Background: Age-dependent immune responses to coronavirus disease 2019 (COVID-19) vaccinations and breakthrough infections (BIs) in young and middle-aged individuals are unclear.

Methods: This nationwide multicenter prospective cohort study analyzed immune responses in participants of the ChAdOx1 (ChAd)-ChAd-mRNA vaccine group using cytometry by time-of-flight, anti-spike protein antibody (Sab) and anti-nucleocapsid antibody (Nab) titers, plaque reduction neutralzation tests (PRNTs), and interferon-gamma (IFN-γ) release assays at various time points.

Results: We evaluated 347 participants with an average age of 38.9 ± 9.4 years (range: 21-63). There was a significant inverse correlation between age and Sab levels after the second dose (slope - 14.96, P = 0.032), and this was more pronounced after the third dose (slope - 208.9, P < 0.001). After BIs, older participants showed significantly higher Sab titers (slope 398.8, P = 0.001), reversing the age-related decline observed post-vaccination. This reversal was also observed in PRNTs against wild-type SARS-CoV-2 and the BA.1 and BA.5 variants. IFN-γ responses increased markedly after the third dose and Bis, but showed a weak positive correlation with age, without statistical significance. Immune cell profiling revealed an age-dependent decrease in the proportions of B-cell lineage cells. The proportions of naive CD4+ and CD8+ T cells were inversely correlated with age, whereas the proportions of mature T cell subsets with memory function, including memory CD4+ T, CD8+ TEM, CD8+ TEMRA, and TFH cells, increased with age.

Conclusions: Age-dependent waning of the serologic response to COVID-19 vaccines occurred even in middle-aged individuals, but was reversed after BIs. IFN-γ responses were preserved, compensating for the decrease in naive T cell populations, with an increase in memory T cell populations.
Files in This Item:
T202405460.pdf Download
DOI
10.1186/s12979-024-00454-z
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Yong Chan(김용찬)
Park, Yoon Soo(박윤수)
Song, Young Goo(송영구) ORCID logo https://orcid.org/0000-0002-0733-4156
Ahn, Jin Young(안진영) ORCID logo https://orcid.org/0000-0002-3740-2826
Lee, Kyoung Hwa(이경화) ORCID logo https://orcid.org/0000-0003-0033-1398
Choi, Jun Yong(최준용) ORCID logo https://orcid.org/0000-0002-2775-3315
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/200521
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