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

Overview

Journal Interact J Med Res

Publisher JMIR Publications

Specialty Biomedical Engineering

Date 2017 Jul 7

PMID 28679488

Citations 4

Authors

Reginald Gorczynski

Geoffrey Hoffmann

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Toward a fractalomic idiotype/anti-idiotypic paradigm.

Chiappelli F, Penhaskashi J Bioinformation. 2023; 18(9):730-733.

PMID: 37426493 PMC: 10326330. DOI: 10.6026/97320630018730.

Immunomodulatory potential of anti-idiotypic antibodies for the treatment of autoimmune diseases.

Pan S, Chia Y, Yee H, Fang Cheng A, Anjum C, Kenisi Y Future Sci OA. 2021; 7(2):FSO648.

PMID: 33437514 PMC: 7787174. DOI: 10.2144/fsoa-2020-0142.

Combined IMIG and Immune Ig Attenuate Allergic Responses in Beagle Dogs.

Gorczynski R, Maqbool T, Hoffmann G J Immunol Res. 2020; 2020:2061609.

PMID: 32377529 PMC: 7191374. DOI: 10.1155/2020/2061609.

Mechanism(s) of prolonged attenuation of allergic responses after modulation of idiotypic regulatory network.

Gorczynski R, Maqbool T, Hoffmann G Allergy Asthma Clin Immunol. 2019; 15:79.

PMID: 31827543 PMC: 6892213. DOI: 10.1186/s13223-019-0393-7.

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