Influenza vaccination promotes stable atherosclerotic plaques in apoE knockout mice.

ABSTRACT

OBJECTIVE: Current evidence suggests a relationship between seasonal Influenza viral infection and cardiovascular disease (CVD). Experimental animals inoculated with Influenza A virus have shown to develop thrombotic complications similar to those seen in humans. Conversely, several epidemiological studies and clinical trials have suggested that Influenza vaccination may have a protective effect on CVD. However, the potential mechanisms behind this protective effect remain unstudied. We aimed to study the effect of Influenza vaccination on atherosclerotic plaque development in apoE(-/-) mice. METHODS AND RESULTS: The effect of immunization with increasing doses of Influenza vaccine (0.38, 1.8, 9 and 45 µg/0.5 mL Vaxigrip®, Sanofi-Aventis) on atherogenesis was compared with that of animals immunized with Pneumo23® (pneumococcus vaccine, Sanofi-Aventis) and control group inoculated with phosphate buffered saline (PBS). Animals vaccinated with 45 µg/0.5 mL Vaxigrip®, (the same dose used to immunize humans adults against Influenza) developed smaller atherosclerotic lesions with lower lipid content but richer in smooth muscle cells and collagen when compared with control animals. Concomitantly, they showed lower levels of interferon gamma (IFNγ), interleukin (IL)-2 and tumor necrosis factor alpha (TNFα) but higher levels of IL-4. Furthermore, we found increased levels of anti-Influenza immunoglobulin (Ig) G1 or anti-Pneumo23® IgM specific antibodies in a time and dose dependent fashion in animals immunized with these vaccines. CONCLUSIONS: 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.