ABSTRACT
INTRODUCTION: Hemorrhagic fever with renal syndrome (HFRS) holds a leading place among natural focal human diseases in Russian Federation. There is no etiotropic therapy for the disease now. The vaccine prophylaxis is the most effective method to control this infection. The main criteria for inactivated vaccines evaluation are its immunogenicity and specific activity.The study purposes were to develop a sensitive and specific real-time PCR method for viral RNA quantification in the inactivated vaccine and to study the correlation between the viral RNA amount and vaccine immunogenicity. MATERIAL AND METHODS: L-segment fragments of the Puumala, Hantaan, and Sochi vaccine strains were selected as diagnostic targets for oligonucleotides and fluorescent probes. The immunogenicity of experimental vaccines was determined by the induction of neutralizing antibodies in BALB/c mice. RESULTS: A highly specific, sensitive and reproducible real-time PCR method has been developed. The analytical sensitivity was 1.24 ± 1.5 x 102 copies/ml for Puumala virus; 1.16 ± 1.4 * 102 copies/ml for Hantaan; 1.32 ± 1.8 * 102 copies/ ml for Sochi, with a virus content of 1.5 ± 0.5 lg FFU/ml; 1.8 ± 0.5 lg FFU/ml and 2.2 ± 0.5 lg FFU/ml, respectively. The viral RNA amount in experimental vaccine preparations inactivated with ß-propiolactone was proportional to the neutralizing antibodies titer observed in mice following the immunization. DISCUSSION: It was found that different virus inactivators differently affects the detected viral RNA amount, but not the vaccine immunogenicity, which indicates the same degree of the immunogenic proteins damage. The direct relationship between the viral RNA copy number and vaccine immunogenicity makes it possible to use this criterion for vaccine dosage preparation. CONCLUSION: The developed method for viral RNA quantification is a promising tool for the specific activity control of the HFRS vaccine.
Subject(s)
Hemorrhagic Fever with Renal Syndrome , Viral Vaccines , Animals , Antibodies, Neutralizing , Antibodies, Viral , Hemorrhagic Fever with Renal Syndrome/prevention & control , Mice , Mice, Inbred BALB C , RNA, Viral/genetics , Real-Time Polymerase Chain Reaction , Vaccines, InactivatedABSTRACT
The roles of genetic and environmental factors in regulating parameters of intelligence and cognitive style were studied. Monozygotic and dizygotic twins were tested three times, at the ages of 6, 7, and 10 years. The Wechsler Intelligence Test, Embedded Figures Test, and Matched Figures Fitting Test were used. Interrelations between the Intelligence Quotient and cognitive style appeared to be Independent of the shared regulatory mechanisms. Genetic correlations between IQ and cognitive style indicate that they are influenced in part by shared and nonshared genetic factors. It is proposed that qualitative changes in psychological features associated with the dynamic features of cognitive activity occur at the age of 7 years.