Neonatal Subcutaneous BCG Vaccination Decreases Atherosclerotic Plaque Number and Plaque Macrophage Content in ApoE−/− Mice

Abstract

Bacille-Calmette Guérin (BCG) modulates atherosclerosis development in experimental animals, but it remains unclear whether neonatal BCG vaccination is pro- or anti-atherogenic. Many animal models differ fundamentally from BCG administration to human infants in terms of age, vaccine preparation, dosing schedule, and route of administration. We aimed to elucidate the effect of neonatal subcutaneous BCG vaccination—analogous to human BCG vaccination—on atherosclerosis development in ApoE−/− mice. At 2 days of age, a total of 40 ApoE−/− mice received either a weight-equivalent human dose of BCG, or saline, subcutaneously. From 4 weeks onwards, the mice were fed a Western-type diet containing 22% fat. At 16 weeks of age, mice were sacrificed for the assessment of atherosclerosis. Body weight, plasma lipids, atherosclerosis lesion size and collagen content were similar in both groups. Atherosclerosis lesion number was lower in mice that received BCG. Macrophage content was 20% lower in the BCG-vaccinated mice (p < 0.05), whereas plaque lipid content was increased by 25% (p < 0.01). In conclusion, neonatal BCG vaccination reduces atherosclerosis plaque number and macrophage content but increases lipid content in a murine model of atherosclerosis. Human epidemiological and mechanistic studies are warranted to investigate whether neonatal BCG vaccination is potentially atheroprotective.

Research progress on specific and non-specific immune effects of BCG and the possibility of BCG protection against COVID-19

“…For example, one study evaluated the effect of subcutaneous BCG vaccination on the development of atherosclerosis in ApoE −/− mice. It was found that BCG vaccination reduced plaque number and macrophage content but increased lipid content in a mouse model of atherosclerosis ( 97 ). Similarly, in another animal study, the treatment of BCG killed by extended freeze-drying significantly reduced the size of atherosclerotic lesions, upregulated IL-10 production, and downregulated the expression of pro-inflammatory cytokines (IL-6, IL-13, and TNF-α) in mice ( 98 ).…”