Preparation, Characterization and Preliminary in vivo Testing of Liposomated Antiidiotypic Antibodies Against Morphine Derivatives

Artificial membrane structures containing medicinal substances are highly promising for the development of new drugs. Liposomal preparations are actively used in medical practice due to their high efficacy and relatively low toxicity. Our aim was to encapsulate anti-idiotypic antibodies into a liposomal composition with the purpose of improving their immunogenic properties. Following the preparation of a liposomal composition by the dehydration/rehydration method using ultrasonic treatment, the size, zeta potential, and loading efficiency of liposomes were investigated. Preliminary in vivo studies were conducted to evaluate the adjuvant properties of liposomes of varying size. Loaded liposomes of the smallest diameter (about 110 nm) showed the potential of enhancing the immune response similar to that obtained using Freund’s adjuvant. These results justify further research into the properties of liposomes loaded with antibodies.

Towards a new kind of vaccine

We present new data showing that normal IgG immune responses comprise the production of two kinds of antibodies, namely anti-foreign and anti-anti-self antibodies. For example, immunization of C3H mice by two rounds of BL/6 skin grafting results in the production of anti-BL/6 antibodies plus antiidiotypic antibodies (C3H anti-anti-C3H) with the latter being detected using antibodies produced in a BL/6 anti-C3H immune response. Similarly, the IgG immune response of C3H mice to tetanus toxoid includes the production of C3H anti-anti-C3H antibodies. Antigen-specific antibodies produced in one alloimmunization plus antiidiotypic antibodies produced in the converse immunization can be used to synergistically induce specific tolerance. We show that infusions of anti-BL/6 antibodies together with BL/6 anti-anti-BL/6 antibodies specifically suppress an immune response to BL/6 lymphocytes in C3H mice. Specific tolerance was measured as suppression of the induction of BL/6-specific cytotoxic T cells. The two kinds of antibodies with complementary specificity are believed to stimulate two populations of T lymphocytes, and co-selection (mutual selection) of these two populations leads to a new stable steady state of the system that has specifically diminished reactivity to BL/6 tissue. Stimulation with a combination of anti-C3H and C3H anti-anti-C3H IgG antibodies furthermore down-regulates inflammation in a mouse model of inflammatory bowel disease. An analogous combination of C3H anti-BL/6 and BL/6 anti-anti-BL/6 antibodies significantly down-regulates tumour growth and metastases in BALB/c mice in the EMT6 transplantable breast cancer model. We conclude that a combination of certain antigen-specific and antiidiotypic antibodies has potential as a new class of vaccines based on the symmetrical immune network theory. This new kind of vaccine does not involve the production of antibodies. The prevention of two important degenerative diseases makes this a potential anti-aging technology.