ATHEROGRIPPE – Effect of two influenza vaccines on the development of atherosclerosis in ApoE−/− mice

Abstract

The scientific interest in influenza vaccine and its cardiovascular protection continues to grow. Clinical data are progressively reinforcing a vaccine-specific effect, an “infection-independent” action, underlined by an immunomodulatory effect. However, there is a lack of biological data to justify influenza vaccination as an athero-protective measure. We aimed to study the effect of Influenza vaccination on atherosclerotic plaque development in apoE(−/−) mice. Thirty-six apoE−/− mice, aged 6 months and fed nonatherogenic chow, were randomized into three groups ( n = 12, 6 males and 6 females). Mice were immunized subcutaneously and boosted once 3 weeks later with Influenza vaccine (60 μg/0.5 mL Vaxigrip®, Sanofi-Aventis) or a solution of 4 soluble recombinant hemagglutinins (HA)(60 μg/0.5 mL) or with phosphate buffered saline. After 3 weeks, mices were started on high fat diet for 12 weeks. Blood samples were collected from submandibular veins before and after each immunisation. At termination, animals were euthanized and aortic sinus, brachiocephalic trunk and thoraco-abdominal aorta were removed from each animal and preserved.Circulating autoantibodies IgG and IgM against native apoB-100 were quantified by an in-house ELISA in plasma samples. Animals vaccinated with 60 μg/0.5 mL Vaxigrip® and recombinant solution showed a better overall aging phenotype. ApoE−/−vaccinated mice showed macroscopically smaller plaques on large arteries (aorta and brachiocephalic trunk) (quantification in progress) compared to control mice (treated only with saline solution). Similarly, vaccinated mices were found to have lower levels of IgM native ApoB100 autoantibodies compared to control group. These results indicate that vaccination against Influenza may protect against the development of CVD by promoting smaller and stable atherosclerotic plaques and by inducing atheroprotective immune responses.