With the control of infectious diseases,ATHEROSCLEROSIS, that is, deposition of lipids in the arterial wall and its resultant damage and complications, through Heart attack and stroke has become one of the major cause of mortality and morbidity.
With the understanding of the immune-mediated inflammatory mechanism of development of atherosclerosis, it is very exciting to think about that this disease can also be controlled by induction of antigen specific immune responses against atherosclerosis by vaccination.
When we think about the vaccination, we first need to understand the mechanism of inflammation and its role in atherosclerosis.
Both innate immunity which does not require an antigenic stimulation and antigenic specific or adaptive immunity plays a major role in development of the atherosclerosis.
Many researchers have dedicated themselves to study the immune mechanism in Atherosclerosis and the possibility of identifying a stimulus for creating a vaccine. Some of these are as follows:-
- One study found, that in mice, who had high lipids, but were deficient in a specific gene known as macrophage colony-stimulating factor gene, which is essential for macrophage survival and proliferation, have markedly reduced atherosclerosis despite severe hypercholesterolemia (1).
- Similarly another group of studies found that the mice which were having high lipids but were deficient in mast cells had reduced inflammation and lesion formation (2–4). Interestingly, 2 of these studies reported lower circulating cholesterol levels in mast cell– deficient mice, suggesting a link between innate mast cell signaling and cholesterol homeostasis (3,4).
Given that immune-mediated inflammation is a cardinal feature of atherosclerosis, it is tempting to consider specific strategies to target immune or inflammatory components whereby we can develop a vaccine for atherosclerosis. Some go the studies have focused on this only.
EXOGENOUS SOURCES OF REACTIVE ANTIGENS
- A reasonable approach to searching for antigens would be to focus on the disease itself: the atherosclerotic plaque. Many foreign antigens, including bacteria such as Mycoplasma pneumoniae, Chlamydia pneumoniae, and Porphyromonasgingivalis and viruses such as hepatitis C virus, enteroviruses, human immunodeficiency virus, and cytomegalovirus, have been identified in atherosclerotic plaques (5). Its possible to focus on these to create the vaccine
- Periodontal pathogens have recently gained attention in the research community, as many are found in human atherosclerotic lesions (5) and have been linked to atherosclerosis (6–9). Exposure of experimental animals to P. gingivalis accelerates atherosclerosis formation (10–12), whereas immunization against P. gingivalis attenuates such pathogeninduced atherosclerosis (13).
- Clinical trial has shown that LDL has got a causative relationship to atherosclerosis which makes LDL and apoB-100 a logical targets for the vaccination therapy.Because LDL is a large, heterogeneous molecule containing a diverse cargo of apolipoproteins, cholesteryl esters, triglycerides, and phospholipids, it would be impractical to use whole homologous LDL as an antigen in a clinically-usable vaccine.
- Subsequent testing revealed that several immunoreactive peptides, including p2, p143, and p210, resulted in a 40% to 70% decrease in atherosclerosis and reduction in plaque inflammation when used in a vaccine formulation in hypercholesterolemic mice (14,15).
The consistent reduction of atherosclerosis after p210 immunization, regardless of how and which form was delivered, strongly suggests that p210 is a promising candidate antigen for potential vaccine formulation for possible future human application.
- Investigators are now using an innovative approach by identifying a potentially pathogenic CD4þ T cell population and used antigen-specific humoral immunity, determined by the specific signature of these CD4þ T cells to block a pro-atherogenic cellular immune response.
- Dendritic cell vaccines is also been investigated because DCs are the most efficient antigen-presenting cells, antigen delivery by DCs into the host should provoke an efficient response.
The heart attack and stroke which are the major killer and are the manifestation of atherosclerosis is going to be controlled by vaccination is going to be the major development of the 21st century and like that of the development of antibiotic in past.
Given the potential of atherosclerosis as a Giant Killer today, it will be most logical to peruse the atherosclerosis vaccine at the fastest pace. Hoping it comes soon.