[When will the new tuberculosis vaccine appear?].

The problem of tuberculosis prophylaxis remains actual for many countries of the world including Russia. The search of candidates for substitution of the only authorized BCG vaccine has been ongoing for some time, because it does not prevent reactivation of the causative agent in the latent stage and causes generalized BCG-infection in individuals with pronounced immune deficiency. In October 2013 in Lille at the European Congress "World Vaccine 2013" results of multi-year projects and trials of around 40 novel tuberculosis vaccine candidates were presented. The article contains a critical analysis of the materials presented at the congress. 12 vaccines have been developed or are being developed for priming. Among those a live VPM 1002 vaccine based on a genetically modified BCG Mycobacterium bovis (HLY+rBCG) strain and an attenuated vaccine based on Mycobacterium tuberculosis (att. MTB-MTBVAC) have passed phase II clinical trials. 17 candidates are being examined as booster vaccines, among those 6 vaccines have passed phase II clinical trials, and are presented by both modified M. bovis strains and partial proteins of M. tuberculosis. Characteristics of the 3 most perspective vaccines have been presented at the congress: VPM 1002, H &H56 and MVA85A. VPM 1002 is the vaccine closest to introduction. This is a live recombinant anti-tuberculosis vaccine based on the BCG strain, its DNA had genes partially deleted, that code synthesis of listeriolysin. The trials have shown that protective effectiveness of the vaccine is significantly higher than the parent BCG due to better induction of CD4+ and CD8+ cells, as well as IFN-γ, IL-18, 12 and other cytokines responsible for cell immunity function against M. tuberculosis.

[IgM, IgG and IgG subclass antibodies to herpes simplex virus in persons of different ages]. / antitela k virusu prostogo gerpesa, otnosiashchiesia k IgM, IgG i podklassam IgG, u lits raznogo vozrasta.

IgM, IgG antibodies to herpes simplex virus and their subclases were investigated in 565 subjects of different age tested at virological laboratories of St. Petersburg in 1996-1997. The majority of these subjects had a history of herpes infection and 21.5% had IgM antibodies to herpes simplex virus (HSV), marker of acute herpetic infection. Besides IgM, IgG1 antibodies can be referred to early antibodies appearing during the acute stage of herpetic infection. The predominant subclass was HSV IgG3 antibodies. As for IgG4, they were completely absent in infants aged under 1 year, were detected in 6.2% children aged under 14 years, and were present in 12.2-12.5% adults.

[Frequency of acute cytomegalovirus infections among people of differing age groups]. / Chastota ostroi tsitomegalovirusnoi infektsii sredi lits raznykh vozrastnykh grupp.

The incidence of cytomegalovirus (CMV) infection was assessed from the presence of anti-CMV IgM in the sera of 1312 children of different age and 250 adults by the Labsystems enzyme immunoassay kit. CMV-specific IgM are rare in newborns (1.3%), but their incidence increases to 5% during the first year of life. These antibodies occur in 5-6% preschool and schoolchildren. The incidence of acute CMV infection is the highest in adults: 15%.

[Development and application of immunoenzyme test-system for the diagnosis of acute cytomegalovirus infection]. / Razrabotka i primenenie immunofermentnoi test-sistemy dlia diagnostiki ostroi tsitomegalovirusnoi infektsii.

Enzyme immunoassay for the detection of IgM antibodies to human cytomegalovirus (CMV) has been developed. Use of horseradish peroxidase conjugated monoclonal antibodies to human IgM helped create a highly specific test system. The rheumatoid factor was removed from the serum by staphylococcal reagent containing protein A. The results of the newly developed assay are in good correlation with the clinical course of the disease and data of polymerase chain reaction and the test making use of the Labsystem. Cytomegalovirus IgM EIA Kit.

[A comparative study of the protective properties of live recombinant and inactivated influenza vaccines made from strain A/Philippines/2/82 (H3N2) in 8- to 15-year-old children]. / Sravnitel'noe izuchenie zashchitnykh svoistv zhivoi rekombinantnoi i inaktivirovannoi grippoznykh vaktsin iz shtamma A/Filippiny/2/82 (H3N2) u detei 8--15 let.

A limited controlled comparative study for the evaluation of the epidemiological efficacy of live recombinant and inactivated virion vaccines from A/Philippines/2/82-like strains of influenza A (H3N2) virus was carried out in schoolchildren of 8 to 15 years of age. During the influenza epidemic of 1987-1988 caused by influenza A/Sichuan/2/87 (H3N2)-like strains and by influenza B virus in 8.2-17% of cases, a statistically significant efficacy index for live influenza vaccine was 1.8 for the laboratory confirmed A (H3N2) cases. In the group vaccinated with the inactivated vaccine the number of serologically diagnosed A (H3N2) cases was 1.6 times lower than in the group receiving placebo, this difference being statistically significant. Thus, under the conditions of significant difference in the antigenic structure of the vaccine and epidemic A (H3N2) strains, both vaccines produced some diminished but statistically significant preventive effect in vaccinated children although its level was below the optimal. Revaccination of some children with a live influenza vaccine from a new A/Sichuan/2/87-like variant of A (H3N2) virus in the autumn of 1988 with reisolation of the vaccine strain also revealed the presence of some, though weak, resistance to this strain in the children vaccinated with both vaccines.

[A comparative study of the inoculation properties of live recombinant and inactivated influenza vaccines made from strain A/Philippines/2/82 (H3N2) in 8- to 15-year-old children]. / Sravnitel'noe izuchenie privivochnykh svoistv zhivoi rekombinantnoi i inaktivirovannoi grippoznykh vaktsin iz shtamma A/Filippiny/2/82 (H3N2) u detei 8--15 let.

This study was carried out to compare reactogenicity, immunogenicity, and efficacy of live attenuated and inactivated influenza vaccines prepared from influenza A/Philippines/2/82-like virus strains. Schoolchildren of a boarding school of Moscow were randomly divided into three groups: (1) vaccinated with a live attenuated vaccine, (2) vaccinated with inactivated influenza vaccine, and (3) given placebo. Both vaccines were well tolerated by the children, with practically no severe general or local reactions. The inactivated vaccine was found to be superior to the live one in its capacity to stimulate humoral immunity studied by HI, EIA, and microneutralization tests. In 69.7% of the children given the inactivated vaccine, seroconversion to the vaccine strain was detected by two or three methods of antibody titration used. Only 35.4% seroconversions were demonstrated in children immunized with the live influenza vaccine. Enzyme immunoassay was found to be a more sensitive but less specific method for antibody titration as compared with HI test whereas microneutralization proved to be more specific but less sensitive for titration of antibodies to influenza A (H3N2) viruses.

Studies on influenza-virus virulence in recombinants between epidemic and vaccine strains.

Influenza virus recombinants between epidemic strains A/Brazil/11/78 (H1N1), A/USSR/382/78 (H3N2) and vaccine strains A/Leningrad/9/46 (H1N1), A/Victoria/35/72/50 (H3N2) have been tested for virulence for humans and albino mice; their genome structure has also been determined. It has been shown that after the replacement of surface antigens of A/Leningrad/9/46 (H1N1) strain by surface antigens of A/Brazil/11/78 (H1N1) or A/USSR/382/78 (H3N2), strains, the virus becomes totally nonpathogenic for mice whereas its virulence for humans is enhanced. The combination in recombinant X/28 (H1N1) of haemagglutinin and neuraminidase of A/Brazil/11/78 (H1N1) virus and othercomponents of A/Leningrad/9/46 virus determines its high affinity to the epithelium of the upper respiratory tract of humans, as well as its marked virulence for seronegative volunteers. Genetic mechanisms of influenza virus virulence and the involvement of surface proteins in its specific manifestations are discussed. It has been shown that pathogenic properties and the affinity of the virus to particular tissues are determined by different genes and their reasortment can result in the appearance of essentially new properties in recombinants.

[Infectivity of influenza viruses for an organ culture of human embryonic trachea and the change in this trait in recombination]. / Infektsionnost' virusov grippa dlia organnoi kul'tury trakhei émbriona cheloveka i izmenenie dannogo priznaka pri rekombinatsii.

The infecting and reproduction activity of epidemic and vaccine strains of influenza virus as well as their recombinants was studied in human embryo trachea culture. At a certain combination of genes the recombinants showed new qualities: increased tropism to cells of the human upper respiratory tract and intensified virus reproduction in these cells. Of special interest was a recombinant containing the inner proteins of A/Leningrad/9/46 (H0N1) virus and external proteins of A/Brazil/11/78 (H1N1) virus. A possible association of the genes of the internal proteins of influenza A/Leningrad/9/46 virus with the intensity of reproduction, and of the genes of surface glycoproteins with the species specificity of this recombinant is discussed.

[Variability of the virulent properties of influenza A viruses in recombination]. / Izmenchivost' virulentnykh svoistv virusov grippa A pri rekombinatsii.

The pattern of redistribution of human virulence in epidemic strains of influenza viruses in recombination with human avirulent strains was studied. In the course of recombination of epidemic and attenuated influenza virus strains variants with different human virulence were obtained. Some recombinants manifested enforced reactogenic properties as compared with the epidemic strain (X/28, M/35, and 0/26--H1N1, and 2P--H3N2). At the same time, recombinants No 19 (H1N1) and 1P (H3N2) with a similar set of surface antigens were innocuous for man after intranasal administration. Using the observed differences in sensitivity to remantadine as a marker of recombination, we obtained several sets of recombinants which had the antigenic structure of surface proteins of epidemic viruses and remantadine sensitivity of the other parent.

[Biological properties and genome structure of recombinant strains of influenza A virus differing in their degree of human virulence]. / Izuchenie biologicheskikh svoistva i struktury genoma rekombinantnykh shtammov virusa grippa A, razlichaiushchikhsia po stepeni virulentnosti dlia liudei.

The genome structure and some biological properties of parental and recombinant strains of influenza viruses differing by degrees of virulence for man were studied. The vaccine A/Leningrad/9/46 (H0N1) strain was shown to be markedly toxic and pathogenic for mice in contrast to influenza A/Brazil/11/78 and A/Victoria/35/72/50 viruses completely devoid of these properties. The recombinants deriving all 6 genes of the inner proteins of influenza A/Leningrad/9/46 strains and hemagglutinin and neuraminidase of the epidemic A/Brazil/11/78 strain have completely lost their pathogenicity for mice but acquired marked virulence for man. No such effect was observed in recombination of A/Brazil/11/78 with another vaccine strain, A/Victoria/35/72/50. It is suggested that the toxic properties of influenza virus are coded for in genes of internal proteins whereas their manifestation in one or another host species depends on the function of surface polypeptides.

[Parent and recombinant influenza virus A strains differing in the degree of remantadine sensitivity]. / Izuchenie roditel'skikh i rekombinantnykh shtammov virusa grippa A, razlichaiushchikhsia po stepeni chuvstvitel'nosti k remantidinu.

The pattern of inheritance in recombination of various degrees of sensitivity of influenza viruses to remantadine was studied and the genes responsible for the manifestation of this character with regard to the degree of the strain sensitivity to the inhibitor were determined. The results suggest that resistance to 10 microgram/ml remantadine in most cases was determined by the inheritance of the gene coding for the membrane protein, whereas the sensitivity to 10 microgram/ml remantadine most frequently correlated with inheritance of hemagglutinin of the strain sensitive to this inhibitor. The resistance to high remantadine concentration was shown to have features of a polygenic marker as indicated by the occurrence of intermediate forms among the recombinants. Influenza A (H1N1) viruses and strains with the antigenic structure of A (H3N2) isolated in 1979-1981 were more resistant to remantadine, in some cases even to subtoxic concentrations of it. Influenza A (H2N2) and A (H3N2) as a rule were sensitive even to low concentrations of inhibitor.

[Analysis of the RNA in different strains of the influenza A virus]. / Analiz RNK raznykh shtammov virusa grippa A.

The degree of affinity of influenza A/WSN/33 and A/Singapore/57 virus genomes was studied by the method of molecular hybridization which showed the presence in their genomes of 54--57% of analogous sequences. The electrophoretic analysis of RNA--RNA hybrids formed in hybridization of both homologous and heterologous virion and virus-induced RNAs of influenza viruses revealed significant differences in base sequences of the IV, V, and VIII fragments of influenza A/WSN/33 virus RNA and the corresponding fragments of influenza A/Singapore/57 virus RNA; the III and VII fragments of these strains have sites also differing in base sequences at the ends of molecules.

[Structure of the genomes of recombinant strains of influenza A viruses with various antigenic and biological properties]. / Struktura genomov rekombinantnykh shtammov virusov grippa A s razlichnymi antigennymi i biologicheskimi svoistvami.

Genomes of influenza A/WSN/33, A/Singapore/57 and recombinant X-7 and X-9 viruses were studied by the method of molecular hybridization followed by electrophoretic separation of RNA-duplexes in polyacrylamide gel. The genome of the recombinant X-7 influenza virus strain was found to contain fragments V and VII of RNA corresponding to fragments of A/Singapore/57 RNA, whereas fragments III, IV, and VIII were derived from influenza A/WSN/33 virus. Recombinant X-9 had fragments III, IV, and VII of RNA similar to those of A/Singapore/57, and fragments V,VIII of RNA derived from influenza A/WSN/33 virus. Resistance to rimantadine in influenza viruses correlated in X-7 and X-9 recombinants to the strain appurtenance of fragment VIII.

Comparative study of the electrophoretic mobility of the RNA of influenza parent and recombinant strains.

The electrophoretic mobility of the RNA of Influenza viruses A/WSN, A/Singapore and their antigenic recombinants X-7 and X-9 was investigated. The genome of each virus studied consisted of seven pieces of RNA. The electrophoretic profile of the influenza virus A/WSN RNA differed from that of A/Singapore but resumbled that of the recombinant X-9 genome. The essential differences were connected with the properties of the fifth fragment of the RNA. The molecular weight of this RNA species of influenza virus A/WSN and X-9 was 5.4 X 10(5) AND 5.3 X 10(5) daltons (d) respectively. The molecular weight of the corresponding component of the influenza viruses A/Sinapore and X-7 RNA was 6.2 X 10(5) and 6.3 X 10(5)d respectively.

[Electrophoretic motility of RNA of recombinant influenza virus strains X-7 and X-9]. / Elektroforeticheskaia podvizhnost' RNK rekombinantnykh shtammov virusa grippa X-7 i X-9

The electrophoretic motilitiy of RNA of recombinant influenza virus strains X-7 and X-9 differing in the antigenic structure of hemagglutinin and neuraminidase was studied. The genome of these viruses was found to be fragmentary and to consist of 7 RNA molecules. Significant differences in the electrophoretic motility of the middle-molecular RNA compounds of influenza X-7 and X-9 virus were demonstrated, particularly of the V fragment the molecular weight of which was lower in influenza X-9 virus.