Development of Technology of Extracorporeal Virus-Specific Immunohemosorbents' Preparation and Study of Their Effectiveness in Complex Therapy with Lymphokines for Treatment of Severe Forms of Hepatitis B and Tick-Bone Encephalitis
Tech Area / Field
- BIO-CGM/Cytology, Genetics and Molecular Biology/Biotechnology
3 Approved without Funding
State Research Center of Virology and Biotechnology VECTOR, Russia, Novosibirsk reg., Koltsovo
- Novosibirsk Scientific Technological Park / JSC "Vector-Best", Russia, Novosibirsk reg., Koltsovo
Project summaryGlobal spreading and grave consequences of virus parenteral infections, such as hepatitis В, С, HIV infection, etc., threaten seriously health of the planet's population. This alarming state is due, to a great extent, to the lack of necessary medications and corresponding clinical procedures of therapy for these diseases at the present time.
In the case of hepatitis B, portal-systemic encephalopathy and hemorrhage syndrome - main signs of development of a grave infection - are due, to a large extent, to intoxication and emergence of immunopathogenic allergic reactions of infectious genesis. Complications of the infection result from serious disorders in the formation of antiviral immunity. In this connection, authors of the project consider extracorporal immunohemosorption in combination with lymphokine therapy a promising method of immunotherapy for severe forms of this and a number of other parenteral infections.
The essence of the new approach lies in the simultaneous removal of infection endotoxins, the infecting agent, allergenic antigens and immunopathogenic complexes from the organism of a patient with the use of hemosorbent for elimination of toxins bearing immobilized antiviral antibodies. During the procedure, immunohemosorbent outside the organism is connected to a patient's blood circulation and serves as a sort of an additional artificial organ of elimination of toxins and antigens. The rapid clinical removal of main infection pathogens from a patient's blood, cells and organs of the immune system improves functional activity of immunocompetent cells. Use of immunohemosorption results in the increase of the organism's receptiveness to the combined immunocorrective therapeutic action of lymphokines-natural modifiers and correctors of the protective immunity during viral infections.
Thus, in scientific and methodological aspects, the work on the project will realize the basic idea of immunotherapy for infectious diseases: overcoming severe infection and leading the patient to the convalescence stage by way of efficient, intensive formation or reconstruction of cellular and humoral links of the infection-injured antiviral immunity with the use of lymphokines. Extracorporal immunohemosorption is used for the efficient elimination of toxins, of the infecting agent and infection-generated allergens, for sanitation of an organism, and thus for potentiating of immunomodulating and immunocorrective properties of lymphokines in the complex therapy. Employment of virus-specific hemosorption and lymphokine therapy is indicated, first of all, for patients in a serious state when advanced acute infection or aggravation of a chronic infection is complicated by a toxicosis and immunopathology. The combined procedure of immunocorrection is also intended for preventing chronization of infection in patients with the corresponding clinical prognosis.
Traditional methods of treatment using administering medicines to the organism often aggravate toxicosis and allergic complications of the infection. Absence of virus-specific sorbents in the medicines market and insufficient study of the new method of treatment to date prevent the broad use of extracorporal immunohemosorption in practice.
The aim of the present project is to develop a production technology of ready-to-use dosage forms of immunohemosorbents using antibodies against hepatitis В and tick-borne encephalitis viruses and a new extracorporal procedure of intensive therapy of severe forms of the diseases by means of immunohemosorption in combination with lymphokine therapy, and to study therapeutic efficiency of the proposed method of treatment for viral infections by clinicolaboratory and clinical methods. Interferon, commonly prescribed for treatment of these infections, is not enough effective, its use being significantly limited in cases when infection is complicated by allergy, high activity of autoimmune reactions; besides, chronic infections require a rather prolonged course of interferon treatment.
In the course of work over the project, the authors plan to prepare specific polyclonal antibodies against hepatitis В and tick-borne encephalitis viruses, monoclonal antibodies against tick-borne encephalitis virus; to develop methods of irreversible immobilization of antibodies on hemosorbents ensuring retention of their immunochemical activity and the sorbents' compatibility with blood; to develop ready-to-use sterile dosage forms of immuno-hemosorbent preparations, and to conduct preclinical and clinical study of their use in combination with natural immuno stimulants and immunomodifiers-lymphokines-for the intensive therapy of hepatitis В and tick-borne encephalitis. A new clinicolaboratory method of a patient's blood incubation in the CO2-incubator under the conditions of regulated exposure to immunohemosorbent and lymphokines will be developed, which is necessary for making prognosis of the development and outcome of an infectious disease, for studying of functional activity of immunocompetent cells and for testing effectiveness of the complex method of immunotherapy for severe infections. Clinical tests of the preparations for complex therapy, laboratory-clinical examinations will be performed using contemporary clinical, biochemical, morphological, immunology and molecular-virological (PCR assay of viral nucleic acids) research methods.
As a result of carrying out the project, technologies for production of ready-to-use dosage forms of virus-specific immunohemosorbent preparations for treatment of hepatitis В and tick-borne encephalitis will be developed. Pilot lots of the preparations will be produced; scientific and technical documents on their production, quality control and on the extracorporal procedure of their use will be prepared and certified. Necessary clinical tests will be carried out, and authorization of the Ministry of Public Health of the Russian Federation will be received for the use of the preparations in clinical practice. The authors of the project will draw up the final scientific report regarding the study of therapeutic effectiveness of the combined use of virus-specific immunohemosorption and lymphokine therapy for intensive treatment of severe forms of hepatitis В and tick-borne encephalitis.
The methodological and technological approach we propose can be used for the creation of a new class of medicines on the base of cellular and genetic engineering preparations bound to a carrier, and for the elaboration of high-efficiency extracorporal immunotherapeutic procedures for treatment of other infections. Thus, realization of this project is expected to expand considerably the market of vitally important medicines and new clinical services for treating widespread severe infectious diseases.
The project was drawn up with the participation of a large group of research workers from various scientific institutions-developers of modern IEA and PCR techniques for medical diagnosis, antiviral vaccines; molecular virologists, genetic and cellular engineers, developers of the new technique for hemosorbent preparation; medical specialists in various fields using in their work up-to-date therapeutic techniques (experts in infectious diseases, immunology, neuropathology, resuscitation, etc.) from specialized departments of hospitals.
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