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Vol. 23, Art. 52 (pp. 856-901)    |    2022       

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Hapten-carrier conjugates with haptens-analogues of psychoactive substances and toxicants: general principles of modeling the specificity of haptene epitopes

Kozlov V.K.1,2*, Bespalov A.Ya.1, Kashuro V.A. 2,3,4

1 Scientific and clinical center of toxicology named after academician S.N. Golikov FMBA of Russia
2 St. Petersburg State University
3 St. Petersburg State Pediatric Medical University of the Ministry of Health of Russia
4 Federal State Budgetary Educational Institution of Higher Education Russian State Pedagogical University. A.I. Herzen u

Brief summary

Based on the analysis of the available literature data and the author's own experience in the field of constructing conjugated antigens with haptens of psychoactive and toxic compounds, the principles of giving hapten epitopes the property of being immunodominant in the composition of antigens (immunogens) are summarized. The main algorithms for ensuring the immunodominance and target specificity of hapten analogs, and, accordingly, the specificity of antibodies obtained in the humoral immune response to such conjugated antigens, are described. It is argued that conjugated antigens with hapten analogues of psychoactive substances and toxicants, being molecular vaccines of a special type, exhibit various biological information in their composition, namely: 1) antigenic determinants of immunochemical specificity, including hapten epitopes and epitopes of a macromolecular carrier; 2) antigenic sites that activate cooperative interactions of immunocompetent cells in the process of antigen recognition and initiation of an adaptive immune response; 3) antigenic sites capable of triggering the process of polyclonal activation of lymphocytes (probably, this statement is not true for all conjugated antigens); 4) antigenic sites identified as PAMP, which are responsible for the manifestation of the property of "internal adjuvant" by the antigen and activate constitutional immunoreactivity (not present on all conjugated antigens); 5) pharmacophore (toxophoric) groups of the hapten-analogue that retained their activity upon chemical conjugation with a carrier. The conjugated antigen (immunogen) exhibiting the listed biological information during active immunization-vaccination triggers the processes of of organism's immunoreactivity. Activation of constitutional immunity system is a preparatory phase of the adaptive immune response, including its humoral component. In the course of the immune response, antibodies specific to the antigen (immunogen) are produced and immunocompetent cells proliferate - numerous clones of lymphocytes with specificity for each specific epitope of the antigen. Having recognized an antigen, the immune system embodies the strategy of response to an antigen and organizes a set of manifestations and mechanisms of immunoreactivity - an immune response that is always specific in its adaptive component, since it is implemented with the involvement of immune factors of individual and strictly specific recognition of immunochemical determinants of antigenic specificity - antigen epitopes, including hapten epitopes of conjugated antigens. In fact, the structure of conjugated antigen (immunogen) programs the organism's response. At the same time, the biological activity of the immunogen, exposed in its structure, predetermines the strategy and choice of immunoreactivity algorithms, the specificity and intensity of the immune response, including antibody production. These characteristics of the organism's immunoreactivity can be controlled by optimizing the quality of the antigen and modeling its structure. A methodology for optimizing the characteristics of conjugated antigens used to obtain reagents for immunochemical analysis, in particular, polyclonal and monoclonal antibodies, is outlined. These antibodies are intended for use in sensitive and specific methods for the quantitative determination of many biologically active low molecular weight compounds - drugs of various pharmacological groups, ecotoxicants and highly toxic poisons. Conjugated antigens with haptens-analogs of psychoactive substances, in particular with haptens-analogs of drugs, are trying to be used as vaccines used to vaccinate drug addicts with the aim of secondary prevention of drug addiction. Studies are also being conducted on the effectiveness of the use of Fab fragments of monoclonal antibodies as therapeutic biotechnological preparations for lethal intoxications with certain drugs and narcotic substances.


Key words

psychoactive substances; narcotic substances; organophosphates; conjugated antigens (hapten-carrier conjugates); design principles; immunochemical specificity; hapten determinants (epitopes); epitope density on the carrier; haptens-analogues of psych

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