Background Angiotensin Converting Enzyme Inhibitors (ACEi) and Angiotensin Receptor Blockers (ARB) have anti-inflammatory properties via decreasing AT1R binding/levels, reducing Reactive Oxygen Species (ROS) and cytokine activation. This study investigated whether these medications can negatively impact hemagglutination inhibition (HAI) responses to influenza vaccination.

Methods Participants, over the age of 18, were consented and enrolled in the study to receive an influenza vaccine during the 2024-2025 influenza season. Participants were classified into individuals on either ACEi or ARB. Healthy controls were selected based on age-sex-body mass index (BMI) matching and a second control group of participants were diagnosed with hypertension (HTN). but on taking these medications. Analysis focused on relative risk ratios (RR) for seroconversion to the influenza vaccine, in addition to day 28 geometric mean titers (GMT), number of seroprotected participants, and fold change was carried out.

Results We observed a lower trend of seroconversion amongst participants taking either medication compared to the HTN controls and did not observe any differences compared to the healthy controls. There were no differences in day 28 GMT, although the HTN controls had statistically significant higher fold changes in HAI titers compared to the healthy controls. Compared to the treatment groups, the HTN controls had a non-significant higher fold change against all three strains included in the influenza vaccine.

Conclusions Overall, the use of medications did not impact seroconversion when compared to healthy controls, but participants did have a lower trend for seroconversion compared to the HTN controls. This could be due to reduced inflammatory markers in people taking these medications, but this reduction in titer is similar to that in healthy participants. More studies comparing inflammatory markers related to medications in people are needed. In addition, determining the impact of the use of ACEi and ARB on lymphocyte responses is critical for effective influenza vaccination strategies.

The authors have declared no competing interest.

This project has been funded by the National Institute of Allergy and Infectious Diseases, a component of the NIH, Department of Health and Human Services, under contract 75N93019C00052.

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WIRB-Copernicus Group Institutional Review Board (WCG IRB #20224877)

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