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Introduction to Vaccination
Published in Mesut Karahan, Synthetic Peptide Vaccine Models, 2021
Nezih Pişkinpaşa, Ömer Faruk Karasakal
If production is given, antibodies that bind to tumor-associated antigens (TAA) are isolated and injected into mice. To the mouse immune system, TAA antibodies are antigens. They cause an immunogenic reaction that can bind to the “TAA idiotype” and produce a mouse antibody called “anti-idiotypic”. The resulting mouse antibodies are inoculated into other mice. The antibodies that appear in the second group of mice have a three-dimensional binding site that mimics the original antibodies that bind to tumor-associated antigens. These antibodies are combined with an adjuvant and administered as a vaccine. Anti-idiotypic antibodies mimic the active antigen to make a copy of it. This method is used in high-risk cancer patients as well as in developing vaccines against pathogens (Büyüktanır 2010) (Figure 2.3).
AI and Immunology Considerations in Pandemics and SARS-CoV-2 COVID-19
Published in Louis J. Catania, AI for Immunology, 2021
Way back in Chapter 2 (page 21) and (page 46) we discussed the very complex system of idiotype antigen-specific B cells increasing through genetic cloning and creating their own immunogenic stimuli which induces anti-idiotype-specific antibodies (“antibodies 1, 2”). This produces an antibody idiotype-specific regulatory circuit also referred to as the “idiotype network theory” (INT). I mentioned that this “regulatory circuit” remains the center of much immunology research including its potential of it providing long-lasting immunity as a vaccine which it has demonstrated for cancer89. To date, there has been little reported on research into this technology’s use with SARS-CoV-2, but it is likely that such research is in its early stages and among the 190 plus worldwide investigations into COVID-19 vaccines.
Human Monoclonal Autoantibodies
Published in Thomas F. Kresina, Monoclonal Antibodies, Cytokines, and Arthritis, 2020
Susan Alpert Galel, Edward G. Engleman, Steven K. H. Foung
Because most of the monoclonal autoantibodies have been generated with the aid of in vitro polyclonal stimulation, it must be demonstrated that the antibodies generated in vitro have relevance to the autoantibodies detected in vivo. Clinical relevance may be demonstrated through a variety of techniques. First, as we have done, one can compare the binding specificity or functional effects of the monoclonal antibodies to those of patient sera. Second, one can look for competitive effects of the monoclonal antibody versus patient sera. Finally, one can generate an anti-idiotype antibody directed against the monoclonal and use this to demonstrate expression of the monoclonal idiotype in patient sera. Shoenfeld et al. used this third approach to identify an idiotype common to many monoclonal anti-DNA antibodies and have demonstrated the expression of this idiotype in a large percentage of patients with SLE both in their serum and at the site of tissue damage (8).
Enhanced immunogenic potential of cancer immunotherapy antibodies in human IgG1 transgenic mice
Published in mAbs, 2022
Jerome Egli, Stefan Heiler, Felix Weber, Guido Steiner, Timo Schwandt, Katharine Bray-French, Christian Klein, Sebastian Fenn, Gregor P. Lotz, Eugenia Opolka-Hoffmann, Thomas E. Kraft, Laetitia Petersen, Rebecca Moser, Jonathan DeGeer, Michel Siegel, Daniela Finke, Juliana Bessa, Antonio Iglesias
The assumption that ADA responses to CEA-mTCB and CEA-IL2v are stimulated by activation of T cells targeted by their mTCB or the IL2v moieties is further supported by immunization experiments with mixtures of scaffold CEA-IgG with purified IL2v or a one-arm variant of the mCD3ε-specific antibody (mCD3-OA). These immunization studies show an incremental difference in immunogenicity comparable to that found with the corresponding T cell engager antibodies (Supplementary Figure 5). From these results, we conclude that idiotype-specific B cell clones exist that are indirectly reactivated by the action of IL2v or CD3ε binder molecules. Given the T cell-activating nature of the IL2v and anti-CD3ε Fab, the question arises whether this reactivation is an antigen-cognate process, or the sole result of bystander responses mediated by nonspecific T cells.
Concerns about the safety of anti-TNF agents when treating rheumatic diseases
Published in Expert Opinion on Drug Safety, 2020
Fabiola Atzeni, Valeria Nucera, Elisabetta Gerratana, Mariateresa Cirillo, Francesca Marino, Gianfranco Miceli, Donatella Sangari, Laura Boccassini, Ignazio Francesco Masala
Anti-TNF ADA, INF and ETN can all induce the development of neutralizing and non-neutralizing anti-drug antibodies that reduce drug concentrations to below therapeutic levels [4]. The structure of monoclonal antibodies includes domains such as the complementarity determining regions, which increase the risk of immunogenicity by involving the idiotype/anti-idiotype network [4]. These immunological characteristics mean that there is a risk that anti-drug antibodies may cause antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity [87], although the latter is more likely in the case of ETN which, even though it has a fragment constant (Fc) domain, is more rigid nature and lacks a heavy chain 1 domain [4]. Furthermore, the new CTZ has a pegylated Fab’ fragment but lacks an Fc domain, and does not seem to induce ADCC or complement-dependent cytotoxicity.
Immune memory limits human longevity: the role of memory СD4+ T cells in age-related immune abnormalities
Published in Expert Review of Vaccines, 2020
Victor Ivanovich Seledtsov, Alexei A. von Delwig
We propose that theoretically, polyclonal immunization with autologous memory T cells could be an effective approach toward prevention of age-related expansion of pathological memory T cells. Concrete cell compositions in such autological memory T cell-based preparations could be determined by individual autoimmune T-cell reactivities on a case-to-case basis. Importantly, there is a large body of literature to suggest that the proposed T cell vaccination is safe and could be clinically effective in the treatment of different autoimmune diseases [59]. Theoretically, T-cells with higher auto-aggressive properties would receive correspondingly more growth preferences in the course of life. Therefore, their idiotypic determinants present in a polyclonal T-cell vaccine are more likely to reach threshold quantitative levels to induce idiotype-specific immune responses. It follows from this notion that the more memory T cells with a particular specificity are present in a particular TCV formulation, the higher the corresponding neutralizing anti-idiotypic immune response is going to develop. Finally, we emphasize that polyclonal autologous T-cell preparations can be readily obtained from any patient on more than one occasion, and such T-cell vaccines could be effective against new auto-aggressive T-cell clones that are likely to have expanded over time.