Antibodies to lipids and liposomes: immunology and safety

Naturally occurring antibodies to phospholipids and cholesterol are widespread; they occur commonly during the course of acute infections; they are not causally related to the anti-phospholipid syndrome; they have been associated with other clinical entities only as an epiphenomenon; and they have not been implicated as causing any clinical syndrome or disease. There are theoretical and experimental reasons to believe that normal cells and tissues are protected from binding of antibodies to bilayer lipids by steric hindrance due to adjacent larger molecules, such as large or charged adjacent glycolipids or proteins on the cell surface. There are also reasons to believe that certain natural antibodies to lipids can even serve useful normal functions. Antibodies to liposomal lipids induced by liposomes containing lipid A appear to have characteristics that are similar or identical to naturally occurring antibodies to lipids, and it is therefore believed that such antibodies would not cause adverse clinical effects. Numerous Phase I and II human clinical trials of experimental vaccines containing liposomes and lipid A have shown a high level of safety.