Atheroprotective effect of influenza vaccine in ApoE-/- mice

Abstract

Atherosclerosis is a chronic inflammatory disease defined by the deposition of plasma lipoproteins in the subendothelial space of large arteries, associated with peripheral inflammation. Recently, influenza vaccination has been shown to have atheroprotective effects and prevent atherosclerosis in clinical studies and animal models, but the underlying mechanisms remain unknown. Our objective was to evaluate the effect of influenza vaccination on the development of atherosclerosis in ApoE (-/-) mice. Considering the association between peripheral inflammation and neuroinflammation, we investigated whether neuroinflammation would be affected by vaccination. 36 ApoE-/- ice were treated with a conventional vaccination protocol with either the conventional influenza vaccine (60 μg/0.5 mL Vaxigrip®, Sanofi-Aventis) or a vaccine solution of 4 soluble recombinant hemagglutinins (60 μg/0.5 mL) compared with a control group treated with PBS solution. Animals immunized with both vaccine solutions showed an improved aging phenotype and survival compared with control mice. These mice developed macroscopically smaller atherosclerotic lesions, without influence on native ApoB100 IgM and IgG autoantibody levels. On neuroinflammation process, our results indicate that, in the hippocampus, the 2 vaccines tested induce a decrease in proinflammatory markers and an increase in antiinflammatory markers. Similar effects seem to be induced by the vaccines in the other brain regions analyzed. Influenza vaccination promotes protection against atherosclerosis and associated neuroinflammation in this model. These initial consistent results between the two vaccines suggest that hemagglutinin is necessary and sufficient to induce the observed beneficial effects.