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Experimental Models of Smallpox

#2339


Development of Experimental Models for Examination of the Efficacy of Medicinal Preparations and Vaccines for Variola Virus

Tech Area / Field

  • BIO-INF/Bioinformatics/Biotechnology
  • BIO-SFS/Biosafety and BioSecurity/Biotechnology

Status
3 Approved without Funding

Registration date
09.10.2001

Leading Institute
State Research Center of Virology and Biotechnology VECTOR, Russia, Novosibirsk reg., Koltsovo

Collaborators

  • Freie Universität Berlin / Benjamin Franklin Medical Center / Institute of Infection Medicine, Germany, Berlin\nFreie Universität Berlin / Benjamin Franklin Medical Center / International Consortium of Blood Safety, Germany, Berlin\nRobert-Koch-Institute, Germany, Berlin

Project summary

The Project was designed in accordance with the decisions of the WHO Advisory Committee on variola virus researches (Geneva, December 6-9, 1999 and February 15-16, 2001). Main goal of the proposed Project is to develop experimental models for examination of mechanisms of activity of the medicinal preparations against variola virus (VarV). The virus housed in the Russian National Collection will be used for the studies during the implementation of the Project.

Replication of VarV is characterized by presence of many steps. This fact determines presence of many points for impact of VarV replication by antiviral agents. Experimental model using cell culture for examination of mechanisms of antiviral activity will be developed. Parameters of VarV infection and propagation of cell culture, and parameters of analysis of mechanisms of antiviral action of preparation will be chosen. The model should allow (a) to detect antiviral activity, and (b) to identify stages of the virus replication affected by a preparation. The experimental model will be tested using one preparation having established activity against VarV.

Necessary step of the examination of antiviral activity is to study this one in animals, in order to be sure that a preparation keeps its antiviral properties inside an organism. For development of such experimental model characteristics of VarV infection in mice will be studied. Mice of different ages genetically resistant and genetically susceptible to mousepox virus (ectromelia virus) will be infected by VarV. A scheme of the testing of preparations against VarV, and a set of parameters for examination of mechanisms of antiviral activity in mice will be established. Antiviral activity of the preparation used for examinations in cell cultures will be studied using developed mouse experimental model in order to check the model applicability. Mechanisms of antiviral action in cell culture and mice will be compared.

Experimental model using non-human monkeys will be developed for examination of antiviral properties of preparations on ground of VarV infection in animals evolutionary close to human. Time course examination of the VarV infection will be performed in one monkey species. Visual signs of the disease, fever and rash evolution will be studied. Blood will be sampled for immunological, hematological and virological studies. Few monkeys will be euthanized during the infection. Visceral organs will be sampled for detection of the virus and for histological examinations in addition to listed studies. Based on the data obtained (a) parameters of the modeling of VarV infection in monkeys, and (b) parameters for analysis of the antiviral action of preparations against VarV on ground of infection in evolutionary close to human animals will be determined.


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