Technical specification for production of a live measles vaccine for oral administration.
Tech Area / Field
- BIO-IND/Industrial Biotechnology/Biotechnology
8 Project completed
Senior Project Manager
Kondratenkov Yu B
State Research Center of Virology and Biotechnology VECTOR / Institute of Molecular Biology, Russia, Novosibirsk reg., Koltsovo
- Département d'immunologie / Laboratoire National de Santé, Luxembourg, Luxembourg\nConnaught Laboratories, Inc., USA\nUniversiteit Rotterdam, The Netherlands, Rotterdam
Project summaryMeasles is dominating among the droplet infections in many countries. More than 60 million people in the world are annually suffering with measles, and over 1.5-2 million of children, mostly of early age, annually die of this disease. In several developing countries the lethality level of this infection reaches 10-32% in certain years. Measles is the vital problem not only for many countries of Africa, Asia, and Latin America, but for the highly developed countries too, since this disease undermines the child's health causing serious aftereffects and opening the way for the other infections.
The only radical measure in the struggle against measles is the immunization of all population sensitive to this infection.
Serious reactions to measles vaccine considerably more uncommon than the aftereffects and complications of the disease itself. Encephalitis occurs only in one case per l million doses of measles vaccine. On the other hand the acute encephalitis occurs in one case per 1000-5000 cases of natural measles. Subacute sclerosing panencefalitis develops considerably rarer after immunization comparing with the natural measles disease. The live measles vaccine is produced in 15 countries of the world. In Russia the Moscow Enterprise on Producing the Bacterial Preparations manufactures the monovaccine against measles on the basis of viral strain L-16, the primary embryonic cell culture of Japanese quails from the leucosisless farm in Estonia being used as the substrate. This enterprise, being the only one in the country, cannot provide the vaccine production according to the modern requirements. The lack of sufficient quantity of the expendable syringes makes the anti-measles vaccination rather dangerous.
We suggest to develop the work in two following directions: (i) changing of the substrate for virus growth in order to obtain the high-quality preparation with stable characteristics; (ii) elaboration of the technology for producing the tabletted form of the live measles vaccine for per os administration, which will increase the vaccination safety and lower its price.
Necessity of substrate substitution is connected with the fact that the only one farm which produces quail embryos free from leucosis virus is located in Estonia. Difficulties of winter transportation, inconvenience of work with the quail eggs, and unsatisfactory quality of the material obtained after trypsinization are the prerequisites for substitution of the substrate. The primarily trypsinazed culture of Japanese quail embryo fibroblasts is suggested to be substituted by cells of diploid strain of human embryo lung L-68, which are controlled according to WHO requirements and have the certificate of national control agency, L.A. Tarasevich State Institute of Standardization and Control (SISC). Such substitution will provide the stable production of vaccine of higher quality.
The main goal of the present project is the elaboration of production technology of the tabletted form of live measles vaccine, performance of the preclinical study of measles vaccine for per os administration, and trials of the preparation in volunteers.