Neonatal Subcutaneous BCG Vaccination Decreases Atherosclerotic Plaque Number and Plaque Macrophage Content in ApoE−/− Mice
by
, , , , and
Siroon Bekkering
1,2,†,
Krishan Singh
3,†,
Hui Lu
4,
Albert P. Limawan
4,5,6,
Claudia A. Nold-Petry
4,7,
Megan J. Wallace
4,6,
Nigel Curtis
1,8,
Salvatore Pepe
1,8,
Michael Cheung
1,8,
David P. Burgner
1,7,8,*,‡ and
Timothy Moss
4,6,‡ 1
Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, VIC 3052, Australia
2
Department of Internal Medicine, Radboud University Medical Centre, 6525 Nijmegen, The Netherlands
3
School of Public Health and Preventive Medicine, Monash University, Clayton, VIC 3800, Australia
4
The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia
5
Fakultas Kedokteran, Universitas Indonesia, Jakarta 16424, Indonesia
6
Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC 3800, Australia
7
Department of Paediatrics, Monash University, Clayton, VIC 3800, Australia
8
Department of Paediatrics, University of Melbourne, Parkville, VIC 3010, Australia
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
‡
These authors contributed equally to this work.
Biology 2022, 11(10), 1511; https://doi.org/10.3390/biology11101511
Submission received: 5 September 2022
/
Revised: 5 October 2022
/
Accepted: 11 October 2022
/
Published: 15 October 2022
(This article belongs to the Special Issue Immunology and Immunotherapy in Cardiovascular Disease)
Simple Summary
Bacille-Calmette Guérin (BCG), the vaccine against tuberculosis, is the most widely used vaccine in the world, given to almost two-thirds of newborns. BCG also has non-specific effects, which affect immune responses more broadly and impact mortality from unrelated infections. It is also important to understand the effects of BCG on other immune-related diseases, such as the development of cardiovascular disease. This has previously been studied in numerous animal studies, but not with an equivalent protocol and BCG dosage to human newborn vaccination. In this study, we vaccinated newborn mice with BCG using a dose, timing and administration route similar to human newborn vaccination. We show that BCG decreases atherosclerosis, both the number of atherosclerotic plaques as well as inflammation within the plaque. Translating our findings to humans, these potentially beneficial effects might be enhanced, as BCG vaccination decreases all infections, and infections are also associated with cardiovascular disease, so BCG could further lower the risk of developing cardiovascular diseases.
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.
Keywords:
atherosclerosis; neonatal vaccination; BCG; inflammation; ApoE−/−
