Poster Presentation & Flash Talk 46th Annual Meeting of the Fetal and Neonatal Physiological Society 2019

Neonatal immunisation against tuberculosis with Bacillus Calmette–Guérin vaccine affects the development of atherosclerosis in Apoliporotein E knockout mice fed a high fat diet. (#159)

Tim Moss 1 , Krish Singh 2 , Albert Limwan 3 , Siroon Bekkering 4 , Warwick Britton 5 6 , Michael Cheung 4 , David Burgner 4
  1. The Ritchie Centre; Department of Obstetrics and Gynaecology, Hudson Institute of Medical Research; Monash University, Clayton, Victoria, Australia
  2. The Ritchie Centre, Hudson Institute of Medical Resaerch, Clayton, Victoria, Australia
  3. Fakultas Kedokteran, Universitas Indonesia, Depok, West Java, Indonesia
  4. Murdoch Children's Research Institute, Melbourne, Victoria, Australia
  5. Centenary Institute; University of Sydney, Sydney, New South Wales, Australia
  6. Centenary Institute; University of Sydney, Sydney, New South Wales, Australia

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. 

  1. Bekkering S, Limawan AP, Nguyen MU, Widiasmoko LK, Lu H, Pepe S, Cheung MM, Menheniott TR, Wallace MJ, Burgner DP, and Moss TJ. Postnatal inflammation following intrauterine inflammation exacerbates the development of atherosclerosis in ApoE(-/-) mice. Clin Sci (Lond) 133: 1185-1196, 2019.