Dept. of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands.
Thromb Haemost. 2011 Nov;106(5):796-803. doi: 10.1160/TH11-05-0369. Epub 2011 Oct 20.
The treatment of atherosclerosis is currently based on lipid lowering in combination with anti-inflammatory therapies that slow the progression of atherosclerosis. Still, we are not able to fully inhibit the formation or progression of atherosclerotic lesions. A very effective strategy in other disease pathologies is vaccination, in which the body is challenged with the culprit protein or micro-organism in order to create a highly specific humoral immune-response. Immunisation can typically be divided into active or passive immunisation. Active immunisation occurs naturally when the body is exposed to certain microbes or antigens, but also artificially in the case of vaccination. Exposure to a microbe or antigen will result in the production of (antigen specific) antibodies. Passive immunisation is defined as the transfer of humoral immunity (as a result of antibody transfer). Another mechanism to ensure immune-protection is tolerance induction. Immune tolerance occurs naturally to prevent immune responses to 'self-antigens', but can also be induced to non-self antigens. Acquired tolerance to foreign antigens is accompanied by suppression of cellular and/or humoral immune response to the introduced antigen. In its most effective way, vaccination can result in a lifelong protection against the targeted pathology, and therefore the development of an atherosclerosis-specific vaccination is of high importance in the future prevention of atherosclerosis. One of the difficulties in developing effective vaccination strategies for atherosclerosis is the selection of a specific antigen to target. So far vaccination strategies have been based on targeting of lipid-antigens, inflammation-derived antigens, and recently cell-based vaccination strategies have been employed; but also the cardiovascular 'side-effects' of infection-based vaccines are worthy of our attention. This review describes the current status-quo on classical antibody associated vaccination strategies but also includes promising immune-modulation approaches that may lead to a clinical application.
动脉粥样硬化的治疗目前基于降脂治疗联合抗炎治疗，以减缓动脉粥样硬化的进展。尽管如此，我们仍不能完全抑制动脉粥样硬化病变的形成或进展。在其他疾病病理中，一种非常有效的策略是接种疫苗，即通过向体内引入致病蛋白或微生物来激发高度特异性的体液免疫反应。免疫接种通常可分为主动免疫和被动免疫。当身体接触某些微生物或抗原时，主动免疫会自然发生，但在接种疫苗的情况下也会人为地发生。接触微生物或抗原会导致（抗原特异性）抗体的产生。被动免疫是指通过抗体转移来转移体液免疫。确保免疫保护的另一种机制是诱导耐受。免疫耐受会自然发生以防止对“自身抗原”的免疫反应，但也可以诱导对非自身抗原的免疫耐受。对异源抗原的获得性耐受伴随着对引入抗原的细胞和/或体液免疫反应的抑制。在最有效的情况下，疫苗接种可以提供针对目标病理学的终身保护，因此开发针对动脉粥样硬化的特异性疫苗对于未来预防动脉粥样硬化具有重要意义。在为动脉粥样硬化开发有效疫苗接种策略方面存在的一个困难是选择特定的抗原进行靶向。到目前为止，疫苗接种策略一直基于针对脂质抗原、炎症衍生抗原的策略，最近还采用了基于细胞的疫苗接种策略；但是，我们也应该关注感染疫苗引起的心血管“副作用”。这篇综述描述了经典抗体相关疫苗接种策略的现状，还包括有希望的免疫调节方法，这些方法可能会导致临床应用。
