Evaluating the effect of the antiPCSK9 vaccine on systemic inflammation and oxidative stress in an experimental mouse model.

BACKGROUND

To investigate whether the antiPCSK9 vaccine can affect the CRP and oxidative stress (OS) during acute systemic inflammation.

METHODS

Male albino mice were randomly divided into three groups: non-treated mice (the sham group), treated with a nonspecific stimulator of the immune response - Freund's complete adjuvant (CFA; the CFA group), and vaccinated mice treated with CFA (the vaccine group). The vaccine group was subcutaneously immunized with the antiPCSK9 formulation, 4 × in bi-weekly intervals. To induce inflammation, all mice were subjected to the CFA challenge after the vaccination plan. The hsCRP level and OS status were evaluated by a mouse CRP ELISA kit and the pro-oxidant antioxidant balance (PAB) assay, respectively.

RESULTS

The vaccine induced a high-titter IgG antiPCSK9 antibody, which was accompanied with a significant PCSK9 reduction (-24.7% and -28.5% compared with the sham and CFA group, respectively), and the inhibition of PCSK9/LDLR interaction (-27.8% and -29.4%, respectively). hsCRP was significantly increased in the vaccine and CFA groups by 225% and 274% respectively, when compared with the sham group; however, it was non-significantly decreased (-18%; p = 0.520) in the vaccine group in comparison with the CFA group. The PAB values indicated that OS was significantly increased in the CFA group (by 72.7%) and the vaccine group (by 76%) when compared to the sham group; however, there was no significant difference in the PAB values between the vaccine and CFA groups.

CONCLUSION

The antiPCSK9 vaccine failed to significantly reduce the serum hs-CRP and OS induced in the CFA-challenged albino mice.