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Phago-immunotherapy of plague

#3055


Emergency Therapy and Prophylaxis of Plague with Specific Bacteriophages and Monoclonal Antibodies

Tech Area / Field

  • BIO-MIB/Microbiology/Biotechnology
  • BIO-CGM/Cytology, Genetics and Molecular Biology/Biotechnology
  • MED-OTH/Other/Medicine

Status
3 Approved without Funding

Registration date
01.06.2004

Leading Institute
Institute of Immunological Engineering, Russia, Moscow reg., Lyubuchany

Supporting institutes

  • State Research Center for Applied Microbiology, Russia, Moscow reg., Obolensk

Project summary

The Aim of the Project.
To validate experimentally the efficacy of a complex application of bacteriophages and highly purified specific antibodies in plague prophylaxis and treatment.

Plague is one of the most dangerous for human infectious disease induced by gram-negative Yersinia pestis bacteria. After events of the 11th September 2001 in New York, the fact that high virulence of Y. pestis at the contemporary level of genetics and biotechnologies creates an actual danger of using this agent as a bioterroristic weapon must be considered. At the time, the protection against plague could be realized via vaccination or antibiotic therapy. Antibiotics can be used both for the treatment and prophylaxis of plague, thus controlling the disease spreading. Finding in natural foci of Mongolia, Madagascar and South Vietnam of antibiotic-resistant Y.pestis strains cause misgivings in respect of the safety of yersinioses antibiotic therapy. Present anti-plague full-cell vaccines are not widely applied in practice and a number of countries do not use them for the reason of their safety. The main drawbacks of anti-plague vaccines are a short-term and low level of induced by them specific protection, the presence of unfavourable side effects and the necessity of regular immunizations. The existent vaccines are considered to be inefficient against pneumonic plague and do not protect against infection with Y. pestis F– strains. New molecular anti-plague vaccines are in the stage of development. After authorization of the new vaccine application, the immunization strategy with such vaccines should essentially lessen the time needed for the development of plague resistance, but it is unlikely that one-time vaccination could provide fast protection in a patient in case of plague post-infection.

That is why the demand in alternative potent treatment means providing fast protection especially in the case of antibiotic-resistant strains of Y. pestis is a topical task. One of the most perspective approaches to the solving of this problem is the development of a phage preparation including virulent bacterial viruses with a lythic effect in respect to Y.pestis. Single bacteriophages can lyse large populations of pathogens including antibiotic-resistant strains. Phages unlike antibiotics do not induce negative side effects in animals and humans. Drawing attention to the prospects of the phagotherapy, the efficacy of plague protection (including its pneumonic form) with monoclonal antibodies specific to F1 (Caf1) and V antigens of Y.pestis should be emphasized, too. Nowadays, when multiple strategies of obtaining antibodies with assigned specificity suited for clinical use is in the process of improvement, there are solid grounds for performing the studies on construction of potent means for anti-plague therapy.

The Project proposed plans the study on the efficacy of combined application of bacteriophages and specific monoclonal antibodies in the solving the problem of plague urgent prophylaxis and therapy. The participant team has a solid experience in construction of similar phage preparations successfully used in medicine and veterinary, is armed with a collection of lysing phages, possesses a technology for obtaining recombinant protective antigens (LcrV, Caf1, Pla, Psn) of Y.pestis and a collection of hybridomas producing monoclonal antibodies against these antigens.

The aims of the Project provide that the phage preparation would comprise some species of bacterial viruses substantially different from each other in particularity of interaction with Y.pestis cell. That means that the phages will have different receptor specificity and different mechanisms of inhibition of cellular synthetic processes via kill-proteins. Application of such combinations of bacterial viruses in the plague treatment will significantly lessen the expectancy of generation of phage –resistant forms in pathogen populations.

Monoclonal antibodies will be evaluated according to their protective properties and then used for a complex application combined with bacteriophages for the plague treatment.


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