2008 James B. Herrick Award and Lecture—Vaccine for Atherosclerosis: Chasing the Holy Grail
Eradication of many infectious diseases is a testament to the powerful impact of vaccines on human health. Atherosclerotic cardiovascular disease remains a leading equal-opportunity global killer, with a considerable toll of human lives and drain on resources. Adoption of a healthy life-style and judicious use of medications and invasive interventions have clearly made a significant difference, but considerable residual risk and burden of disease remain a challenge. New preventive and therapeutic paradigms deserve to be explored if we are to make heart attacks, strokes, and ischemic sudden cardiac death a thing of the past. In that spirit, our laboratory at Cedars Sinai in Los Angeles, in collaboration with Prof Jan Nilsson’s laboratory in Sweden, has been exploring immunomodulation as a new strategy against atherothrombotic cardiovascular disease. Experimental observations have demonstrated a pro-atherogenic as well as athero-protective role of both innate as well as the adaptive immunity. Among various auto-antigens implicated in atherogenesis, we have focused on oxidized low-density lipoprotein. In the late 1990s, our laboratory and that of Dr Witztum at University of California at San Diego independently first reported the athero-protective effects of oxidized low-density lipoprotein immunization in hyperlipidemic rabbits; these findings have since been corroborated by other investigators in murine models. Recently, we have identified numerous antigenic sequences in human Apo B 100, and some of these sequences, when incorporated into a vaccine formulation, have produced substantial athero-protective and vascular anti-inflammatory effects in mice. These observations, coupled with the demonstrated athero-regressive effects of monoclonal antibodies against some of the Apo B 100 epitopes, have raised the tantalizing possibility that a vaccination strategy against atherosclerosis may not be just a pipe dream, but a potentially novel way to keep the pipes clean.