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. 2025 Jul 1;10(1):132.
doi: 10.1038/s41541-025-01196-9.

Age-associated defect in ADCC response to COVID-19 vaccine

Benjamin L Sievers  1   2   3 , Mazharul Altaf  1   3 , Mark T K Cheng  1   3   4 , Kimia Kamelian  1   3 , Claire Cormie  1   3 ; CITIID-NIHR BioResource COVID-19 Collaboration; Rainer Doffinger  5 , Ravindra K Gupta  6   7   8
Collaborators, Affiliations

Age-associated defect in ADCC response to COVID-19 vaccine

Benjamin L Sievers et al. NPJ Vaccines. .

Abstract

We investigated age-associated effects of SARS-CoV-2 vaccination in elderly individuals (n = 50, mean age 79) after six SARS-CoV-2 vaccine doses. While neutralization titers remained comparable across age groups, Fc-mediated effector functions declined with age. Individuals >80 demonstrated reduced antibody-dependent cellular cytotoxicity (ADCC), via a surrogate ADCC-signaling assay, correlating with diminished IgG1 binding. These findings highlight age-related impairments in Fc-mediated responses, with implications for immune protection and vaccine strategies in older populations.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Serum neutralising antibody titres to SARS-CoV-2 variants of concern following dose 6 of COVID-19 vaccine.
A Top, Study design. Schematic of vaccine timeline highlighting the sixth dose. Fifty-one individuals vaccinated against SARS-CoV-2 with mRNA-based vaccines and/or AZD1222 and/or sub-unit vaccine. B Schematic design of pseudovirus neutralization assay. C Neutralization titers (pNT50) stratified by age against Wu-1 D614G WT, BA.1, BA.2, XBB1.5, BA.2.86, and JN.1. D pNT50 stratified by vaccine-type at dose 6. E pNT50 stratified by sex. Multiple Mann-Whitney compare rank tests with Holm-Šídák corrections were performed to determine significance. *p < 0.05, **p < 0.005, ***p < 0.0005. NS, not significant.
Fig. 2
Fig. 2. Binding serum antibody titres following dose 6 of COVID-19 vaccine.
A Total anti-spike IgG binding antibody responses (multiple Mann-Whitney compare rank test with Holm-Šídák corrections: ***p < 0.0005). B Anti-spike IgG1 binding stratified by age. C Correlation coefficient between IgG1 S correlated with age. D Correlation coefficient between IgG2 S and age, non-significant. E Correlation IgG3 S and age, non-significant. F Correlation coefficient between IgG4 S and age, non-significant. Scatter plots show linear correlation line, and statistical significance was assessed by Pearson’s Correlation.
Fig. 3
Fig. 3. Serum antibody dependent cellular cytotoxicity activity against SARS-CoV-2 spike expressing cells following dose 6 of COVID-19 vaccine.
A Schematic of the antibody-dependent cellular cytotoxicity (ADCC) assay. B Antibody-dependent cellular cytotoxicity assay stratified by age. Mann-Whitney test was used. ***p < 0.0005. C log(ADCC signaling units) correlated with age. **p < 0.005 . D Correlation coefficients between log(ADCC signaling units) and anti-spike IgG1. **p < 0.005. Scatter plots show linear correlation line, and statistical significance was assessed by Pearson’s Correlation.
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