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.
View: Text | PDF
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

×

Figure 4

Monocytes were metabolically reprogrammed after vaccination.

Options: View larger image (or click on image) Download as PowerPoint
Monocytes were metabolically reprogrammed after vaccination. (A) A diagr...
(A) A diagram showing the breakdown of glucose to pyruvate via the glycolytic pathway. Pathway intermediates are shown in black, enzymes are shown in green, and the enzymes analyzed in this study are shown in red. Monocytes were enriched from healthy donor PBMCs on the day before (day –1) and days 14, 56, and 83 after vaccination using a hyperosmotic Percoll gradient. (B–E) Relative expression of transcript levels of (B) GPI, (C) PFKFB3, (D) GAPDH, and (E) PKM2 are shown. (F and G) Isolated monocytes were stimulated ex vivo with (F) medium or (G) irradiated M. tuberculosis (10 μg/mL iH37Rv), and the concentration of IL-1β in the supernatant was measured by multiplex ELISA. (H) Relative expression of transcript levels of ATP5B, a gene marker of oxidative phosphorylation, was also determined. Gene expression was determined using RT-qPCR. Each dot represents an individual donor (n = 6–8), with blue dots denoting male donors and pink dots denoting female donors. Statistically significant differences between the groups were determined by (B–E and H) a mixed-effects model (REML) ANOVA, with Šídák’s multiple comparisons test and (G) a repeated measures 1-way ANOVA using Dunnett’s multiple comparisons test; *P < 0.05, **P < 0.01.