[Group enterovirus infection due to coxsackievirus A16 in Northwestern Russia].

AIM: Study features of epidemic process and etiology of oral cavity and limb enterovirus exanthema group diseases in a number of territories of Northwestern Russia. MATERIALS AND METHODS: Isolation and identification of non-poliomyelitis enteroviruses from material of patients was carried out according to WHO recommendations. Phenotyping and phylogenetic analysis of enteroviruses was carried out. RESULTS: In 3 territories of Northwestern Russia oral cavity and limb enterovirus group diseases were registered. Children aged less than 14 years, predominately aged less than 3 years, were shown to be involved in the epidemic process. Coxsackie A16 enteroviruses from 27 samples of patients were isolated in cell cultures and identified by using specific sera. Coxsackie A16 enteroviruses from 16 samples were identified by using partial sequencing of VP1 genome area. Phylogenetic analysis has shown that the identified Coxsackie A16 viruses distributed among 2 phylogenetic groups. CONCLUSION: Coxsackie A16 enteroviruses that had never been detected in the region previously were established to be the etiologic factor of oral cavity and limb enterovirus exanthema group disease in the 3 territories of Northwestern Russia. The data obtained give evidence on the necessity of epidemiologic and virological control for enterovirus infection with the aim of obtaining novel information on the circulation of non-poliomyelitis enteroviruses in the population and the establishment of development patterns for epidemic process of this infection.

[Immunity to polioviruses in children population of various territories of the Russian Federation].

AIM: Analyze the state of population immunity to polioviruses in children population of 14 administrative territories of the Russian Federation. MATERIALS AND METHODS: Antibody titers against reference vaccine poliovirus serotypes 1, 2 and 3 were determined by using neutralization reaction in cell culture Hep-2. RESULTS: Several years after the termination of conduction of National immunizations days the percent of seronegative children was shown to increase, especially to poliovirus serotype 3, in most of the territories. Possible reasons for fluctuation of geometric mean antibody titers against polioviruses in children in various territories as well as in various years in the same territory were established. CONCLUSION: Quality vaccine prophylaxis and control of population immunity state among children population play an important role in the maintenance of Russian Federation status as a country is free from poliomyelitis.

[The role of epidemiologic surveillance of migrants in the system of poliomyelitis control].

AIM: Analysis of results of virological study of material from children of migrants and evaluation of intensity of immunity against polioviruses in these children. MATERIALS AND METHODS: 1668 feces samples from patients with acute flaccid paralysis and contact individuals and 479 feces samples from healthy children from families of migrants, as well as 1012 blood sera of children aged 3 - 4 and 14 - 15 years living in the same territory of Russia, and 169 blood sera of children of migrants were studied. Polioviruses and non-polio enteroviruses were isolated by standard procedures recommended by WHO in 3 cell cultures - RD, L20B and Hep-2. Virus identification was carried out by microneutralization test with rabbit antisera against poliomyelitisvirus, RIVM (Bilthoven, Netherlands). For intra-type differentiation EIA and PCRwere used. Antibody titers were determined in microneutralization reaction with reference poliovirus vaccines strains in Hep-2 cell culture. RESULTS: The frequency of detection of polioviruses in children of migrants was significantly higher than in patients with acute flaccid paralysis. In a larger percent of cases children of migrants did not have protective antibody titers against polioviruses of all the 3 serotypes. CONCLUSION: Migrants as a significant source of poliovirus detection may be an indicator group for detection of signs of unfavorable epidemic situation. Based on the results of epidemiologic surveillance of migrants the fact of import of wild poliovirus into North-West of Russia with the absence of poliomyelitis was proven, which confirms an important role of this form of monitoring in the system of poliomyelitis control.

[Characterization of vaccine polioviruses isolated in the closed pediatric collective bodies (children's homes)].

Examination of 281 healthy vaccinees from 6 children's homes could isolate 37 vaccine polioviruses. The detection rate for polioviruses in the children's homes, in which there were children born to HIV-positive mothers, was significantly higher than that in other children's homes. These children's homes showed the longest poliovirus excretion after vaccination. The RFLP analysis showed that 40% of the strains being examined were intertypic recombinant strains. The sequence analysis demonstrated that about 30% of the strains under study had a small number of nucleotide substitutions in the VP3-VP1 genomic region. The study revealed a correlation between the dynamics of poliovirus excretion after oral vaccination and the kinetics of formation of recombinant poliovirus strains.

Spread of vaccine-derived poliovirus from a paralytic case in an immunodeficient child: an insight into the natural evolution of oral polio vaccine.

Sabin strains used in the manufacture of oral polio vaccine (OPV) replicate in the human organism and can give rise to vaccine-derived polioviruses. The increased neurovirulence of vaccine derivatives has been known since the beginning of OPV use, but their ability to establish circulation in communities has been recognized only recently during the latest stages of the polio eradication campaign. This important observation called for studies of their emergence and evolution as well as extensive surveillance to determine the scope of this phenomenon. Here, we present the results of a study of vaccine-derived isolates from an immunocompromised poliomyelitis patient, the contacts, and the local sewage. All isolates were identified as closely related and slightly evolved vaccine derivatives with a recombinant type 2/type 1 genome. The strains also shared several amino acid substitutions including a mutation in the VP1 protein that was previously shown to be associated with the loss of attenuation. Another mutation in the VP3 protein resulted in altered immunological properties of the isolates, possibly facilitating virus spread in immunized populations. The patterns and rates of the accumulation of synonymous mutations in isolates collected from the patient over the extended period of excretion suggest either a substantially nonuniform rate of mutagenesis throughout the genome, or, more likely, the strains may have been intratypic recombinants between coevolving derivatives with different degrees of divergence from the vaccine parent. This study provides insight into the early stages of the establishment of circulation by runaway vaccine strains.

[The induction of an immune response to influenza virus antigens by anti-idiotypic antibodies]. / Induktsiia immunnogo otveta k antigenam virusa grippa antiidiotipicheskimi antitelami.

The present investigation indicate that homologous polyclonal anti-idiotypic antibodies induce both humoral and cell-mediated immune response. Experiments on the exhaustion of immune sera with vaccine have revealed that anti-idiotypic antibodies induce not only specific antibodies to influenza virus antigens, but also antibodies to other epitopes of the globulin molecule of the anti-idiotype. Anti-idiotypic antibodies, when reintroduced into animals, induce the production of anti-influenza antibodies of the anamnestic type, but do not induce the formation of antihemagglutinins. The injection of influenza vaccine to animals, previously immunized with anti-idiotypic antibodies, induces the production of antihemagglutinins; an increase in the level of immune complexes and antibodies to anti-idiotype, i.e. anti-idiotypic antibodies, induces the development of immunological memory with respect to influenza virus antigens, including antihemagglutinins.

[Anti-influenzal antibodies inducing an immune response to the influenza virus]. / Protivogrippoznye antitela, indutsiruiushchie immunnyi otvet k virusu grippa.

The injection of anti-influenza antibodies into rabbits induces a specific immune response, including the production of anti-idiotypic antibodies and then the production of immune complexes and anti-influenza antibodies. The injection of antibodies induces the development of immunological memory; as a result, the animals are primed to respond to the injection of influenza vaccine.

[The anti-idiotypic response to the experimental administration of the inactivated or live influenza virus]. / Antiidiotipicheskii otvet na vvedenie inaktivirovannogo ili zhivogo virusa grippa v éksperimente.

The injection of inactivated and live influenza virus into rabbits induces the formation of anti-idiotypic antibodies, appearing after anti-influenza hemagglutinins, in the blood. The presence of immune complexes antibody--anti-idiotypic antibody in the blood of the animals has been established. The booster immunization of the animals with influenza virus antigens produces a rise in the levels of both idiotypic and anti-idiotypic antibodies. The injection of autologous anti-idiotypic globulin into the primed animals ensures the induction of idiotypic and anti-idiotypic revaccinal reactions.

[Immunobiological characteristics of impurities in corpuscular influenza vaccines]. / Immunobiologicheskaia kharakteristika primesnykh komponentov korpuskuliarnykh grippoznykh vaktsin.

Admixtures of free antigens have been shown to play the main role in the anaphylactogenic danger of vaccines. The immunogenic and anaphylactogenic action of such antigenic admixtures in corpuscular influenza vaccine can be observed after the immunization of animals in 2 or 3 injections. Host antigens incorporated into viral particles induce no anaphylactic reaction in guinea pigs after their immunization in 3 injections.

[Analysis of the immunochemical purity of modern influenza vaccines]. / Analiz immunokhimicheskoi chistoty sovremennykh grippoznykh vaktsin.

Corpuscular influenza vaccines have been found to contain chick embryo antigens differing from ovalbumin in their antigenic, immunogenic, and allergenic properties. The study has revealed that host antigens are present in vaccines in the form of free contaminants and as substances incorporated into viruses. The vaccine prepared by the method of sorption-elution on red blood cells with subsequent gel chromatography is characterized by the highest antigenic purity.

[Sensitizing action of nonvirion admixtures in inactivated influenza vaccines in an experiment]. / Izuchenie sensibiliziruiushchego deistviia nevirionnykh primesei v inaktivirovannykh grippoznykh vaktsinakh v éksperimente.

The side-effect of nonvirion admixtures in inactivated influenza vaccines has been experimentally studied. The minimal sensitizing dose of allantoic admixtures other than ovalbumin has been experimentally determined in vivo. This dose has proved to be 4 times higher than the sensitizing dose of ovalbumin. The presence of sharply defined correlations between the concentration of the admixtures contained in inactivated influenza vaccines, the titers of antibodies to these admixtures and the severity of anaphylactic reactions has been established in guinea pigs after their multiple immunization.

[Safety and effectiveness study of the aerosol method of administering inactivated influenza chromatographic vaccine in an experiment]. / Izuchenie bezvrednosti i éffektivnosti aérozol'nogo metoda vvedeniia inaktivirovannoi grippoznoi khromatograficheskoi vaktsiny v éksperimente.

Experiments in laboratory animals demonstrated safety, areactogenicity, and low allergenic potential of inactivated influenza chromatographic vaccine (IICV) administered by aerosol method. Aerosol immunization of white rats resulted in the development of the same level of secretory antibody as after intraperitoneal inoculation of IICV but the immunizing aspirational dose was 10-20 times as low as parenteral. Marked protection of mice was achieved after triple aerosol immunization of immunologically experienced animals.

[Cellular immune reactions to the multiple administration of a chromatographic inactivated influenza vaccine in an experiment]. / Kletochnye immunnye reaktsii na mnogokratnoe vvedenie inaktivirovannoi grippoznoi khromatograficheskoi vaktsimy v éksperimente.

The administration of inactivated chromatographic influenza vaccine to mice in three injections induced the formation of the pronounced clone of antigen-reactive lymphocytes, detected in the leukocyte blast transformation test. Slight fluctuations in the phytohemagglutinin level and lipopolysaccharide response in mice subjected to multiple immunization with the inactivated vaccine indicated that this preparation produced no damaging effect on the T- and B-lymphocyte populations.