Immunity & Ageing (Jul 2024)

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

  • 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

DOI
https://doi.org/10.1186/s12979-024-00454-z
Journal volume & issue
Vol. 21, no. 1
pp. 1 – 11

Abstract

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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+ 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.

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