ПАТОГЕННОСТЬ И ИММУНОГЕННОСТЬ ВАРИАНТОВ ВИРУСА ОСПОВАКЦИНЫ ПРИ РАЗНЫХ СПОСОБАХ ИХ ВВЕДЕНИЯ МЫШАМ

Vaccinia virus had been played a key role in the global smallpox eradication. But in the course of mass vaccination using several vaccinia virus strains were revealed hard side effects with lethal outcomes in some cases, especially in humans with immunodeficiency. Therefore after declaration in 1980 about smallpox eradication World Health Organization recommended to stop smallpox vaccination. After last 40 years the most part of Earth human population does not have immunity not only against smallpox, but also against any other zoonotic orthopoxvirus infections, such as monkeypox, cowpox, buffalopox, and camelpox. All of these represent increasing danger for human health and heighten risk of emergence of highly contagious virus caused by natural evolution of existed zoonotic orthopoxviruses. In order to prevent development of small outbreaks into spreading epidemics and, thus, to decrease a risk of emergence due to natural evolution of highly pathogenic for humans orthopoxviruses, researchers’ efforts should be applied to development of safe live vaccines of new generation based on vaccinia virus with target virulence genes inactivation. These strains should be studied in laboratory animal models using different routes of virus inoculation. Vfccinia virus attenuation now usually is achieved in the course of live recombinant vaccines creation as specific DNA sequences insertion into virus virulence genes and their inactivation. The subjects of this research were vaccinia virus strain LIVP, used in the Russian Federation as smallpox vaccine, and attenuated variant LIVP-GFP created on its basis by genetic engineering methods with inactivation of thymidine kinase gene. These viruses were intracerebrally inoculated into suckling mice in doses 10 1 or 10 2 PFU/animal for neurovirulence assessment. Adult mice were infected intranasally, subcutaneously or intradermally in doses 10 7 or 10 8 PFU/animal and clinical manifestations were analyzed during 14 days. On 28 day of the experiment samples of blood sera were collected from mice individually and ELISA technique was used for analyses of virus specific antibodies levels. It was shown that recombinant vaccinia virus strain LIVP-GFP caused very low neurovirulence and pathogenicity for mice in comparison with parental LIVP. The most safe and effective route of immunization by studied vaccinia virus strains is intradermal inoculation.