Vaccination with prevenar (R) boosts the production of anti-phosphorylcholine antibodies and protects apoe knockout mice from atherosclerosis

Even, G.; Kiss, M.; Laschet, J.; Ozvar Kozma, M.; Simon, T.; Wigren, M.; ... ; Caligiuri, G. (2018)

Article / Letter to editor

Phosphorylcholine (PC) is an oxidation-specific epitope present on oxidized LDL and apoptotic cells, as well as the capsular polysaccharide of Streptococcus pneumoniae. PC is bound by naturally occurring IgM antibodies and low levels of anti-PC IgM are a risk factor for atherosclerosis. Active immunization of atherosclerosis-prone mice with oxidized LDL, S. pneumoniae or PC conjugated to keyhole lympet hemocyanin (PC-KLH) induces high titers of anti-PC Abs and protects from atherosclerosis. However, it is unknown if existing vaccine preparations can be exploited as preventive vaccine in atherosclerosis. Our aim was to evaluate the potential atheroprotective effect of Prevenar®, a clinical-grade pneumococcal vaccine.

Male apolipoprotein E-/-,mice (n=10 per group) were injected subcutaneously with 50μl Prevenar® (diluted 1:10 in PBS) at 8 and 12 weeks of age. PC-KLH and PBS were used as positive and negative controls, respectively. Mice were fed regular chow for the entire study. Serum anti-PC Abs were analyzed at baseline and 15 days after the second injection. After 20 weeks serum lipid levels were measured and atherosclerotic lesion size was quantified in the aortic root.

Both vaccination with Prevenar® and PC-KLH induced high titers of anti-PC IgM and IgG Abs and resulted in reduced atherosclerosis compared to PBS injected mice (figure) despite similar serum cholesterol levels.

The amount of residual PC in Prevenar® is sufficient to elicit atheroprotective anti-PC responses in apoE-/- mice. Since Prevenar® is already used in humans, its potential to prevent atherosclerosis and/or slow down atherosclerosis progression could readily be tested in clinical trials.

• Oxidized LDL
• Polysaccharide
• Streptococcus pneumonia
• Atherosclerosis
• Pneumonia
• Hemocyanin
• Apolipoprotein
• Aortic root
• Vaccination.

• All authors: Even, G.; Kiss, M.; Laschet, J.; Ozvar Kozma, M.; Simon, T.; Wigren, M.; Gaston, A.; Procopio, E.; Le Borgne-Moynnier, M.; Nilsson, J.; Kuiper, J.; Nicoletti, A.; Binder, C.; Caligiuri, G.
• Date: 2018-08-31
• Volume: 275
• Pages: E6 - E7
• DOI: doi:10.1016/j.atherosclerosis.2018.06.903