Journal Article

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

Bae, Seongman, Kim, Shin-Woo, Kim, Eu Suk, Choi, Won Suk, Jeong, Hye Won, Lee, Kyoung Hwa, Choi, Jun Yong, Park, Sehee, Kwon, Sook Jin, Koh, June-Young, Ahn, Jin Young, Song, Young Goo, Peck, Kyong Ran, Kang, Eun-Suk, Gerelkhuu, Zayakhuu, Ko, Jae-Hoon, Kim, Yong Chan, Song, Kyoung-Ho, Yoon, Tae Hyun, Kim, Sung-Han, Kwon, Ki Tae, Park, Yoon Soo

2024

Overview

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 + T EM , CD8 + T EMRA , and T FH 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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Age groups / Aging / Analysis / Antibodies / B cells / Biological response modifiers / Biomedical and Life Sciences / Biomedicine / Body mass index / CD4 antigen / CD8 antigen / Cell lineage / Cell-mediated immunity / Clinical Nutrition / Coronaviruses / COVID-19 vaccines / Cytometry / Ethylenediaminetetraacetic acid / Geriatrics/Gerontology / Health aspects / Health care / Humoral immunity / Immune response / Immune response (humoral) / Immunity / Immunological memory / Immunology / Infection / Interferon / Lymphocytes B / Lymphocytes T / Mass cytometry / Memory cells / Middle age / mRNA / mRNA vaccines / Nucleocapsids / Older people / Pandemics / Public Health / Regression analysis / RNA / Severe acute respiratory syndrome coronavirus 2 / Software / Spike protein / T cells / Vaccination / γ-Interferon