Background: Atherosclerosis is an inflammatory vascular disease that originates in early life and its development is influenced by early life immune challenge (1). The effects of BCG vaccination in adult experimental animals are inconsistent, and the effects of neonatal vaccination are unknown.
Method: Neonatal mice (2 days of age) received a single subcutaneous injection (10 µl) of either BCG vaccine (0.5 x 104 colony forming units; n=19 from 3 pregnancies) or saline (controls; n=15 from 4 pregnancies). At 4 weeks mice were weaned onto a high fat (22%) diet; at 16 weeks plasma and tissues were collected for analysis. Atherosclerosis was assessed histologically. Plasma lipids were analysed by ELISA. Data (presented as mean+/-SEM) were compared between groups using analysis of covariance with sex and litter as covariates.
Results: Body and organ weights at 16 weeks were not different between BCG and control groups. Cross-sections of the aortic sinus wall of BCG-treated mice contained a greater proportion of lipid (20.2+/-4.2%) than control (15.8+/-2.6%; p=0.02) and a greater proportion of collagen (37.0+/-2.0% v. 29.3+/-2.3%; p=0.06). BCG-treated mice had a greater proportion of lipid in cross-sections of the brachiocephalic artery (16.7+/-2.0%) than controls (11.0+/-2.5%; p=0.08). Plasma cholesterol concentrations were higher in the BCG group (678+/-30 mg/dl) than controls (606+/-39 mg/dl; p=0.03).
Conclusion: Neonatal BCG vaccination increases atherosclerosis in ApoE knockout mice fed a high-fat diet.