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Immun Ageing . Overcoming the age-dependent SARS-CoV-2 vaccine response through hybrid immunity: analysis of humoral and cellular immunity with mas

tetano

Editor, Senior Moderator
Immun Ageing


. 2024 Jul 30;21(1):51.
doi: 10.1186/s12979-024-00454-z. Overcoming the age-dependent SARS-CoV-2 vaccine response through hybrid immunity: analysis of humoral and cellular immunity with mass cytometry profiling

Zayakhuu Gerelkhuu[SUP] #[/SUP][SUP] 1 2 [/SUP], Sehee Park[SUP] #[/SUP][SUP] 3 [/SUP], Kyoung Hwa Lee[SUP] #[/SUP][SUP] 4 [/SUP], Yong Chan Kim[SUP] #[/SUP][SUP] 5 [/SUP], Sook Jin Kwon[SUP] 6 [/SUP], Kyoung-Ho Song[SUP] 7 [/SUP], Eu Suk Kim[SUP] 7 [/SUP], Young Goo Song[SUP] 4 [/SUP], Yoon Soo Park[SUP] 5 [/SUP], Jin Young Ahn[SUP] 8 [/SUP], Jun Yong Choi[SUP] 8 [/SUP], Won Suk Choi[SUP] 9 [/SUP], Seongman Bae[SUP] 10 [/SUP], Sung-Han Kim[SUP] 10 [/SUP], Shin-Woo Kim[SUP] 11 [/SUP], Ki Tae Kwon[SUP] 12 [/SUP], Hye Won Jeong[SUP] 13 [/SUP], Kyong Ran Peck[SUP] 14 [/SUP], Eun-Suk Kang[SUP] 15 [/SUP], June-Young Koh[SUP] #[/SUP][SUP] 16 [/SUP], Jae-Hoon Ko[SUP] #[/SUP][SUP] 17 [/SUP], Tae Hyun Yoon[SUP] #[/SUP][SUP] 18 19 20 21 22 [/SUP]



Affiliations
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 neutralization 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[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cells were inversely correlated with age, whereas the proportions of mature T cell subsets with memory function, including memory CD4[SUP]+[/SUP] T, CD8[SUP]+[/SUP] T[SUB]EM[/SUB], CD8[SUP]+[/SUP] T[SUB]EMRA[/SUB], and T[SUB]FH[/SUB] 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.

Keywords: Aging; COVID-19 vaccines; Immunity; Mass cytometry.

 
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