Justified is the possibility of application of fixed rabies virus Moscow 3253, reproduced on the cell culture Vero, as an antigen for heterologous anti-rabies immunoglobulin production. Application of the adjuvant - aluminium hydrate - is determined to be effective. Herein, by the day 73 post immunization, specific antibodies titer is ≥ 1:500 (wherein specific activity has been identified by means of neutralization test, carried out on white mice, and dot-blot immunoassay). The level of specific activity in experimental samples of anti-rabies immunoglobulin, isolated from rabbit immune serum, corresponds to 332 and 347 ME/ml. Physicochemical and biological properties of anti-rabies immunoglobulin, produced with the help of cultural antigen, fully comply with regulatory requirements specified for commercial preparation of heterologous anti-rabies immunoglobulin.

Presented is a comprehensive approach to utilization of the wastes that appear in the process of heterologous anti-rabies immunoglobulin production (packed red cells, fibrin, and alcohol-containing products). Specific immunoglobulin is extracted from the surface of red blood cells using desorption technique. Additional yields of immunoglobulin after exposure of erythrocytes to non-ionic detergent amount to 10-19 % of the output. Rich protein supplement feeding for horses-producers is obtained from spray-dried packed red cells. Solid nutritious substrate for microbiological media production is obtained from fibrin using enzymic hydrolysis method. The efficiency of the fibrin hydrolysate-based media is 1.5-2 times higher in comparison with that of the media based on the digest of meat and casein, as demonstrated by the results of Vibrio cholerae scaled cultivation. Furthermore, worked out is the technology of ethanol regeneration after the rivanol-ethanolic precipitation of gamma globulin, alcohol content by volume being (93±1) % after the regeneration. It is demonstrated that the regenerated alcohol can be used as a precipitator in the process of anti-rabies serum fractioning. All in all, the developed techniques make it possible to utilize the wastes of anti-rabies immunoglobulin production and provide for further use of derivatives while producing medical immunobiological preparations.

Presented are the comparative data of actual and regulated indicators of the qualitative characteristics of the heterologous anti-rabies immunoglobulin produced by the RARI Microbe for the five years of serial preparation manufacturing. Modern high-technology methods to control the baromembrane processes used in immunoglobulin purification are highlighted.

week after immunization (specific activity is identified using neutralization reaction on the model of white mice and dot-blot immunoassay). This level of activity is sufficient for the fractioning of immune serum and extraction of anti-rabies immunoglobulin. Physicochemical and biological properties of the anti-rabies immunoglobulin, obtained with the help of cultural antigen technique, meet the requirements stated in the normative documentation on anti-rabies immunoglobulins extracted from equine blood serum. Specific activity level of experimental batches of anti-rabies immunoglobulin, obtained with the help of cultural technologies, corresponds to 242 and 214 IU/ml.

Экспериментальное оБоснование внедрения культуральных технологий в производство антираБического иммуноглоБулина ФКУЗ «Российский научно-исследовательский противочумный институт «Микроб», Саратов, Российская Федерация В обзоре представлены основные итоги научно-исследовательской и опытно-конструкторской работы, выполненной при реализации федеральной целевой программы «Национальная система химической и биологической безопасности» (2009-2014) по разработке и внедрению культуральных технологий в производство антирабического иммуноглобулина. Освещены основные этапы разработки методологии масштабного культивирования фиксированного вируса бешенства, концентрирования культуральной жидкости, количественного обнаружения вируса бешенства с применением ПЦР, иммунизации продуцентов. Получение пилотных серий усовершенствованного антирабического иммуноглобулина, соответствующего нормативным требованиям на коммерческий препарат, свидетельствовало об эффективности разработанных биотехнологических, методологических приемов, а также разработанного проекта производственно-технологической документации.