Trained immunity is induced in humans after immunization with an adenoviral vector COVID-19 vaccine
Dearbhla M. Murphy, … , Joseph Keane, Sharee A. Basdeo
Dearbhla M. Murphy, … , Joseph Keane, Sharee A. Basdeo
Published October 25, 2022
Citation Information: J Clin Invest. 2023;133(2):e162581. https://doi.org/10.1172/JCI162581.
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Clinical Research and Public Health

Trained immunity is induced in humans after immunization with an adenoviral vector COVID-19 vaccine

Abstract

Background Heterologous effects of vaccines are mediated by “trained immunity,” whereby myeloid cells are metabolically and epigenetically reprogrammed, resulting in heightened responses to subsequent insults. Adenovirus vaccine vector has been reported to induce trained immunity in mice. Therefore, we sought to determine whether the ChAdOx1 nCoV-19 vaccine (AZD1222), which uses an adenoviral vector, could induce trained immunity in vivo in humans.Methods Ten healthy volunteers donated blood on the day before receiving the ChAdOx1 nCoV-19 vaccine and on days 14, 56, and 83 after vaccination. Monocytes were purified from PBMCs, cell phenotype was determined by flow cytometry, expression of metabolic enzymes was quantified by RT-qPCR, and production of cytokines and chemokines in response to stimulation ex vivo was analyzed by multiplex ELISA.Results Monocyte frequency and count were increased in peripheral blood up to 3 months after vaccination compared with their own prevaccine controls. Expression of HLA-DR, CD40, and CD80 was enhanced on monocytes for up to 3 months following vaccination. Moreover, monocytes had increased expression of glycolysis-associated enzymes 2 months after vaccination. Upon stimulation ex vivo with unrelated antigens, monocytes produced increased IL-1β, IL-6, IL-10, CXCL1, and MIP-1α and decreased TNF, compared with prevaccine controls. Resting monocytes produced more IFN-γ, IL-18, and MCP-1 up to 3 months after vaccination compared with prevaccine controls.Conclusion These data provide evidence for the induction of trained immunity following a single dose of the ChAdOx1 nCoV-19 vaccine.Funding This work was funded by the Health Research Board (EIA-2019-010) and Science Foundation Ireland Strategic Partnership Programme (proposal ID 20/SPP/3685).

Authors

Dearbhla M. Murphy, Donal J. Cox, Sarah A. Connolly, Eamon P. Breen, Aenea A.I. Brugman, James J. Phelan, Joseph Keane, Sharee A. Basdeo

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Figure 2

Long-term effects of vaccination on monocyte subsets in the blood.

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Long-term effects of vaccination on monocyte subsets in the blood. Monoc...
Monocytes were isolated from PBMCs from healthy donors on day –1 (prevaccine), day 14, day 56, and day 83 after vaccination (and prior to the second dose) using a hyperosmotic Percoll gradient. (A) Cells were Fc blocked and stained with fluorochrome-conjugated antibodies specific for CD14, CD68, and CD16. Total monocytes were identified as CD14+CD68–, and CD14+CD16+ monocytes were also examined. Numbers in the dot plots indicate the frequencies of cells (%) present inside the gate or quadrant. (B) The median fluorescent intensity of CD14 in the total ex vivo CD14+ population was assessed over time. (C) The absolute number of CD14+ cells was calculated by multiplying the total cell yield from the hyperosmotic Percoll enrichment by the percentage of CD14+ cells. (D) Monocyte frequency was calculated by dividing the total number of CD14+ cells by the total number of PBMCs. (E) The absolute number of CD14+CD16+ cells was calculated by multiplying the total cell yield from the hyperosmotic Percoll enrichment by the percentage of CD14+ CD16+ cells. (F) CD14+CD16+ monocyte frequency was calculated by dividing the total number of CD14+CD16+ cells by the total number of PBMCs. Each dot represents an individual donor (n = 10), with blue dots denoting male donors and pink dots denoting female donors. Data are graphed as the mean value ± SD. Statistically significant differences between the groups were determined by repeated measures 1-way ANOVA using Dunnett’s multiple comparisons test; *P < 0.05, **P < 0.01.