[A live vaccine against tick-borne encephalitis: the principles of selecting the vaccinal strains]. / Zivaia vaktsina protiv kleshchevogo éntsefalita: printsipy otbora vaktsinnykh shtammov.

The comparative, semiquantitative, pathomorphological study of the neurovirulence of clones of Elantsev virus and Langat virus TP-21 for intracerebrally infected monkeys has been carried out. The study has revealed that the viruses may be differentiated by their neurovirulence for primates according to the average statistical data on the degree of pathomorphological changes in the central nervous system, but not to maximum lesions in cerebral structures. The level of neurovirulence of yellow fever virus 17D was formerly considered to be the highest admissible limit of residual neurovirulence of encephalitogenic viruses (flaviviruses). According to our data, Elantsev virus, used for the immunization of humans and known to have caused some cases of encephalitis, is similar to yellow fever virus with respect to its neurovirulence for primates: therefore, a candidate strain intended for the preparation of tick-borne encephalitis (TBE) vaccine must be significantly less neurovirulent. The neurovirulence of clones isolated from Langat virus TP-21 has proved to be essentially lower than that of Elantsev virus clones. Langat virus TP-21 is a promising source of clones suitable for use as candidates for live TBE vaccine. Search for vaccine strains by testing their neurovirulence in experiments on several strains of mice and their hybrids, on hamsters and on immunosuppressed animals is methodologically groundless. The adequate evaluation of the level of residual neurovirulence of viruses to be used as candidates for live TBE vaccine can be made only on monkeys.

[The molecular mechanism of the action of antiviral preparations in the adamantane series]. / Molekuliarnyi mekhanizm deistviia antivirusnykh preparatov adamantanovogo riada.

Regions of possible interaction between remantadine and transmembrane M2 protein are revealed by analysis of amino acid substitutions in remantadine- and deutiforin-resistant influenza viruses. The major region includes 5-6 amino acid residues at position 25-31, partially involving the premembrane region and the first position of a hydrophobic membrane-associated domain. The proposed model action of remantadine and its derivatives suggests that remantadine is included into the cell membrane lipid bimolecular layer by its adamantane share and its positively charged NH2-group is exposed to the cell surface. This allows remantadine and its analog to be regarded as molecular "hindrances" for viral particle decapsidation and budding.

[The antiviral activity of deitiforin in experimental para-influenza infection]. / Protivovirusnaia aktivnost' deitiforina pri éksperimental'noi paragrippoznoi infektsii.

Deitiforin in HEp-2 cell culture was shown to inhibit replication of the reference PIV-3 strain when administered 1 hour before virus inoculation. The most marked effect of the drug was observed in the first 4 days of observation. In experimental newborn mice infected with parainfluenza virus 3 deitiforin protected the animals from developing the infection. In humans given deitiforin reaction to vaccination was found to develop 5-6 times more rarely than in the control group, PIV-3 could be isolated twice as rarely, and a diagnostically significant rise of specific antibody levels was observed less frequently.

[Effect of remantadine on the immunodepressive action of influenza virus]. / Vliianie remantadina na immunodepressivnoe deistvie virusa grippa.

Inoculation of mice with strains of influenza virus toxigenic or pathogenic for these animals resulted in significant inhibition of formation of the antibody-producing cells in response to inoculation with sheep erythrocytes. Inoculation of mice with influenza virus strains having no toxicity or pathogenicity for mice did not lead to the development of immunosuppression. The treatment of mice with remantadine prevented inhibition of formation of antibody-producing cells.

[Effect of viral respiratory infections on the development and course of bacterial sepsis]. / O vliianii virusnykh respiratornykh infektsii na vozniknovenie i techenie bakterial'nogo sepsisa.

Sepsis was diagnosed in 9.5%-14.1% of fatalities in children. It was more frequently umbilical and caused by staphylococci, although of late mixed bacterial microflora was not infrequently detected. In 39 observations studied in detail sepsis was combined with acute respiratory infections (ARI) among which most important were viral respiratory infections (AVRI) as well as mycoplasmosis. The most important was the fact that AVRI not only were conducive to the generation of sepsis but caused its exacerbation. In the latter cases the development of fresh septic metastases was observed. This was associated with local (vascular damage) and general (disorders in the immunological status) changes in the patients arising as a result of AVRI.

[Experimental model of associated influenza-para-influenza infection]. / Eksperimental'naia model'assotsirovannoi grippozno-paragrippoznoi infektsii.

An experimental model of associated influenza-parainfluenza infection has been developed. Simultaneous inoculation of mice with influenza A2/21/65 and parainfluenza type 3 or inoculation with these viruses at an interval of 24 hours was shown to produce a considerably more severe disease as manifested by the development of severe confluent pneumonias involving both lungs and death of the inoculated animals. The animals with the associated infection showed no significant difference in antibody titers or the intensity of immunity as compared with control groups (influenza or parainfluenza monoinfection). The development of the mixed infection was accompanied by the inhibition of neutrophilic and macrophage phagocytosis and inhibition of interferon production.

[Comparative study of the antiviral activity of rimantadine and bonafton]. / Sravnitel'noe izuchenie protivovirusnoi aktivnosti rimantadina i bonaftona.

The results of the study on toxicity and the antiviral activity of bonaphthone and rimantadine are presented. A high toxicity of bonaphthone for developing chick embryos was demonstrated, the maximum non-toxic dose of bonaphthone being about 10 microgram/embryo, while for rimantadine it was above 1000 microgram/embryo. In white mice, however, the toxicity of these two drugs was approximately similar. The minimal single lethal dose for mice by the oral route was 400-500 mg/kg for rimantadine and bonaphthone, by the intraperitoneal route 65 mg/kg for bonaphthone and 125 mg/kg for rimantadine. Bonaphthone had a slight prophylactic activity protecting mice inoculated with A2/Bethesda/63 influenza virus. The index of effectiveness of bonaphthone was about 40%, that of rimantadine under similar experimental conditions over 90%. Bonaphthone had no therapeutic effect. It inhibited multiplication of A2/Hong Kong/68 influenza virus in the lungs of mice inoculated with minimal doses of the virus, but was inactive in case of infection of mice with A/Port Chalmers/73 virus. Thus, the comparative study of bonaphthone and rimantadine revealed no superiority of bonaphthone.

[Pathogenetic mechanisms of tick-borne encephalitis]. / Nekotorye patogeneticheskie mekhanizmy progredientnykh form kleshchevogo éntsefalita

The main cause of progressive forms of tickborne encephalitis is a prolonged persistence of certain viral strains in the brain. Although there are no virals with a selective capability to lead only to an acute or chronic encephalitis, nevertheless in the epidemiological process there is a selection of virals capable of bringing on chronic forms of the disease. In cases of an incapacity of immunological factors bor a defence during the initial phase of the infectious process there may be prerequisites to a fixation of the virals in the brain and a chronic development of the neuroinfections. It is necessary to differentiate active neuroinfectious processes due to persistent virals and postencephalitic reparative-dystrophical syndromes. This permits to avoid a hyperdiagnosis and more reasonably select therapeutical measures in the evaluation of their effectivity.

[Study of formation of amantidine and rimantidine resistant variants of influenza A2 subtype virus]. / Izuchenie formirovaniia rezistentnykh k amantadinu i rimantadinu variantov virusa podtipa A2

Passages of influenza A2/Hong Kong/68 in developing chick embryos in the presence of amantadine and rimantadine were carried out and demonstrated rapid development of a resistant virus line under these conditions. Changes in the sensitivity of the virus to the drug were due to selection of resistant particles from genetically inhomogenous original virus strain. The rate of formation of the resistant population was shown to be clearly dependent upon the amount of amantadine inoculated into embryos. The resulting resistant lines retained this property throughout multiple virus passages in embryos without the drug. These biological and antigenic properties of the resulting variants did not differ from those of the initial A2/Hong Kong/68 strain.

Material for the study ofvariation in the Malayan Langat virus (TP-21 strain).

The lack of genetic uniformity of the Malayan Langat virus, TP-21 strain isolated from Ixodes granulatus ticks in Malaya, was demonstrated.Increased pathogenicity of the virus for white mice and rhesus monkeys after passage through chick-embryo fibroblast cultures at temperatures of 36 degrees C and 40 degrees C is due to the selection of the pathogenic virus particles which are always present in the initial brain-tissue suspension of the TP-21 Langat strain.The frequency of the occurrence of pathogenic clones and their selection rate was studied in relation to the conditions of cultivation. A study was also made of the genetic stability and basic biological properties of pathogenic and non-pathogenic clones of the Langat virus.

Experience in the study of a live vaccine made from the TP-21 strain of Malayan Langat virus.

The reaction-causing properties and immunogenicity of 2 cloned variants of the Malayan tick virus, Langat TP-21 strain, were studied. One clone, which was not pathogenic for rhesus monkeys when inoculated intracerebrally, caused the formation of antibody in moderate titre against tick-borne encephalitis virus in over 70% of persons given 2 inoculations of a live vaccine prepared from it. The other variant, which was pathogenic for rhesus monkeys, was characterized by greater immunogenicity but when given as a live vaccine caused acutely febrile reactions and other side-effects in 10% of inoculated persons 6 to 8 days after administration.In persons vaccinated with the avirulent vaccine, the antibodies were maintained for over 3 years compared with only 1 year after administration of a killed vaccine. The live vaccine made from the non-pathogenic clone of the Langat virus proved to be suitable for revaccinating patients inoculated with the killed vaccine. The vaccine prepared from the non-pathogenic clone could be more extensively employed for the prophylaxis of tick-borne encephalitis.