Toward a New Kind of Vaccine: A Logical Extension of the Symmetrical Immune Network Theory

BACKGROUND: The symmetrical immune network theory, developed in 1975, is based on the existence of specific T cell factors and hypothesizes that normal IgG immune responses comprise the production of 2 kinds of antibodies, namely antigen-specific antibodies and anti-idiotypic antibodies. OBJECTIVE: The aim of this study was to confirm the existence of specific T cells factors and to show that immunization of C3H mice with BL/6 skin or using nominal antigen for immunization (Tetanus Toxoid) induced production of antigen-specific (anti-BL/6 or antitetanus) antibodies plus anti-idiotypic antibodies (C3H anti-anti-C3H). Subsequently, we investigated the role of combinations of antigen-specific and anti-idiotype antibodies in a variety of animal models of clinical diseases. METHODS: Antigen-specific antibodies were produced by conventional immunization of mice (eg, with tetanus toxoid or by skin allografting). Subsequent anti-idiotypic antibodies were derived by exhaustive absorption of antigen-specific antibody, with confirmation of anti-idiotypic specificity by binding to relevant target antigen-specific antibodies in an enzyme-linked immunosorbent assay (ELISA). Antigen-specific plus anti-idiotypic antibodies were then used to modulate skin allograft survival, dextran sulfate sodium (DSS)-induced colitis, ovalbumin (OVA)-induced IgE production, and breast cancer growth in mice. RESULTS: Infusions of anti-BL/6 antibodies together with BL/6 anti-anti-BL/6 antibodies specifically suppressed (>85%) an immune response to BL/6 lymphocytes in C3H mice. The two kinds of antibodies with complementary specificity are hypothesized to stimulate 2 populations of T lymphocytes. Coselection of these 2 populations leads to a new stable steady state of the system with diminished reactivity to BL/6 tissue. A combination of anti-C3H and C3H anti‑anti-C3H IgG antibodies down-regulated inflammation in a mouse model of inflammatory bowel disease (>75%) and attenuated anti-IgE production and sensitization to produce IL4 cytokines (>70%) in an OVA-allergy model. Combination of C3H anti‑BL/6 and BL/6 anti-anti-BL/6 antibodies decreased tumor growth and metastases (>705) in an EMT6 transplantable breast cancer model. CONCLUSIONS: Use of a combination of antigen-specific and anti-idiotypic antibodies has potential as a new class of vaccines.