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Anti-Rubella Vaccines and Diagnostics

#2439


Diagnostic and Vaccine Preparations on the Base of Virus-Like Particles of Rubella Virus

Tech Area / Field

  • MED-VAC/Vaccines/Medicine
  • MED-DID/Diagnostics & Devices/Medicine
  • BIO-INF/Bioinformatics/Biotechnology
  • BIO-CGM/Cytology, Genetics and Molecular Biology/Biotechnology
  • BIO-CHM/Biochemistry/Biotechnology

Status
8 Project completed

Registration date
04.03.2002

Completion date
19.01.2007

Senior Project Manager
Weaver L M

Leading Institute
Research Center of Molecular Diagnostics and Theraphy, Russia, Moscow

Supporting institutes

  • State Moscow Plant for Bacterial Preparations, Russia, Moscow

Collaborators

  • Columbia University / Mailman School of Public Health, USA, New York\nCenter for Biologics Evaluation and Research/US Food and Drug Administration, USA, MD, Rockville

Project summary

Description.

Along with the evident effect of vaccine prophylactic of rubella disease with the use of attenuated strains, there have been revealed quite serious counter-indications. Among detected counter-indications in vaccinated people most often occurring ones are post-vaccine arthritis and arthralgies, that manifest themselves within 1 - 6 weeks after vaccination. Attenuated vaccine virus is a cause of a sub-clinical infection and may persist for quite a long time in the organism of vaccinated people, that can, in its term, lead to unpredicted outcome. In general live vaccine against rubella disease, just like many other viral vaccines, can cause side effects, the reason for which in particular, is the injection of hostile RNA into the human organism. All this activates researchers to look for alternative genetically engineered vaccines. Such perspective directions are the development of vaccines, constructed on the base of virus-like particles (VLP). VLP can be used as an antigen while constructing highly specific diagnostic preparations and at production of polyclonal and monoclonal antibodies, the use of which will widen the embrace of immunoassay. Immunoassay development tendencies at the present moment are directed to the simultaneous use of a big variety of antibodies with different affinity aiming at the increase of specificity for antigen and multicomponent mixture analysis.

The scientific level achieved.

The applicant Institution for the suggested project has performed experimental approbation of laboratory eukaryotic strain, producing VLP. Purified VLP may be used for obtaining of recombinant vaccine and highly specific diagnostic preparations. This conclusion is based on the following experimental data: in the reaction of haemagglutination inhibition and immunoassay VLP bind antibodies in a similar way to a native virus. Injection of mice by VLP induced the antibodies formation. It was proved by a method of electron microscopy that according to the outlook and size VLP do not differ from the native virus. The investigation by the method of immunoblotting also proved the presence of all the 3 structural proteins in VLP. This is vital for getting a profound immune response of VLP as a vaccine preparation.

Nevertheless the laboratory VLP producing strain does not correspond to the manufacturing requirements, first due to a low productivity of VLP and, second- because of elimination of the plasmid from producing cells in the course of their reproduction. It is required to launch a complex investigation for construction of new genetic- engineering vector systems for the development of a sound VLP producing strain and wide immuno-biological trials of diagnostic and vaccine preparations on the base of VLP.

To this end the object of the present project is a creation of new genetically engineered vector constructions, that allow to obtain highly expressed VLP producing strain and a profound immuno-biological testing for the development of diagnostic and vaccine preparations on the base of VLP.

The implementation of the project.

To achieve the goal of the project it is suggested to transfer a previously obtained cDNA, coding a block of rubella virus structural genes, into an expression vector on the base of a retrovirus. This will permit to reach the cDNA integration into a genome of a host-cell after the vector transfection into eukaryotic cells. This approach allows excluding the abortion of a hostile genetic material from potential VLP producing cells. In addition, modern vector constructions on the base of retroviruses make it possible to multi-copy the incorporation of hostile DNA fragments into the genome of the host-cell (from 100 up to 1000 copies), which may increase the expression capacity of the producing strain 10-fold and more. In the course of the project implementation it is suggested to develop an industrial technology of VLP isolation and purification. The antigen obtained is suggested to use for the obtaining of experimental vaccine batches for immunisation of most adequate laboratory animals, including pole cats and green monkeys.

Unique approach to the solution research problems.

The suggested complex technical and scientific solution of the problem of production of recombinant vaccine and diagnostic preparations on the base of VLP has no analogies in the world. There are a number of investigations in this field but of a rather persified and fragmental nature.

Intermediate results:

– development of highly expressive eukaryotic VLP producing cells;


– development of industrial technology of VLP isolation and purification;
– development and certification of monoclonal antibodies to different epitopes of rubella virus structural proteins;
– production of experimental batches of vaccine preparations;
– testing of the vaccine obtained on the models of laboratory animals (ferrets and marmosets);
– development of immuno-biological diagnostic preparations.

In the course of the project fulfilment all the necessary information for the application of the In the course of the project implementation all necessary information for the application of the recombinant vaccine against rubella virus into the medical practice will be provided.

In addition, there will be developed and applied in the health care system new generation of immunodiagnostic preparations.

A bank of monoclonal antibodies, that allows to perform serotyping of different rubella virus strains, circulating in endemic regions will be created. The investigation of specificity of humoral immune response in humans towards the agent - rubella virus will be performed.

Possible outcome of the project.

The developed vaccine and diagnostic preparations could be used for epidemiological situation assessment in cities and rural regions as well as for mass vaccination.

Co-operation potential after the project implementation.

A joint development and technical specification of production of commercial preparations on the base of rubella virus VLP.


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