[A comparative study of live and inactivated influenza vaccines: the organization of the observation and the results of a study of their reactogenicity and immunogenicity]. / Sravnitel'noe izuchenie zhivoi i inaktivirovannykh grippoznykh vaktsin: organizatsiia nabliudeniia i rezul'taty izucheniia reaktogennosti i immunogennosti.

Schoolchildren of 30 to 34 schools of Novgorod were vaccinated over a three-year period with Russian live cold-adapted attenuated vaccine for children and whole-virus inactivated vaccines and placebo for comparative field study of the vaccines properties and efficacy. In control trials both bi- and trivalent live attenuated vaccines were well tolerated and areactogenic. A whole-virus inactivated trivalent vaccine induced mild and moderate fever and local reactions in 2-4% of the vaccinees. Special observations are necessary to establish the possibility of use and to determine a dose of this inactivated vaccine for immunization of children, especially those of 7-10 years of age. All the vaccines induced HI antibody production in 50-80% and antineuraminidase in 50-70% of seronegative children. The pattern of the results was similar to that in revaccinated children with preexisting antibody at a level of 1:20, but much lower in children with the initial titre above 1:20. After the 3rd year of vaccination the immune response of the vaccinees was similar, most of the results depending on the initial antibody titre and also on the change of vaccine strains. This raises a question of the expediency of annual influenza revaccination of the same person after 2 years of successful immunization and of the necessity of vaccine strains replacement after 2-3 years of use.

Comparison of live attenuated and inactivated influenza vaccines in schoolchildren in Russia: I. Safety and efficacy in two Moscow schools, 1987/88.

The performance of two doses of cold-adapted live attenuated vaccine versus one dose of whole-virus inactivated vaccine was compared in 8-15-year-old schoolchildren in two schools in Moscow, Russia, during the winter of 1987/88. Both vaccines gave rise to low frequencies of associated febrile or systemic reactions, but the inactivated vaccine, delivered by jet injector, did cause small local reactions in about half of the children. Immunogenicity was higher for both vaccines in antibody-free children, and higher levels of serum antibody were detected following use of inactivated vaccine. During the winter, influenza A (H3N2) and influenza B viruses circulated in Moscow. A clear outbreak of (H3N2) virus occurred in both schools, and infections with type B virus also occurred in one school. The influenza A/Philippines/2/82 (H3N2) component of both vaccines exhibited protective efficacy of about 40% (p < 0.05) against serologically proven infection caused by the antigenically drifted A/Sichuan/2/87 (H3N2)-like epidemic viruses in one school. In another school where illnesses associated with antibody rise were documented, efficacy was seen for both vaccines in reduction of illnesses, and of illnesses with serological evidence of infection, but statistical significance was not achieved.

[The use of the lectin test for detecting antineuraminidase antibodies in the sera of vaccinated subjects]. / Ispol'zovanie lektin-testa dlia vyiavleniia antineiraminidaznykh antitel v syvorotkakh vaktsinirovannykh.

The lectin test (a microvariant) was used to study the immunogenicity of live attenuated and inactivated virion divaccines of influenza A (H1N1 + H3N2) and influenza B vaccines in children 3 to 15 years of age. A good correlation was found between the general level of seroconversion of antineuraminidase and antihemagglutinin antibodies in the sera examined. This method is simple and may be useful for titration of large numbers of sera in studies on the immunogenicity of influenza vaccines or peculiarities of anti-influenza humoral immunity.

[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.

[The protective action of arbidol during a rise in respiratory diseases in 1990]. / Izuchenie zashchitnogo deistviia arbidola vo vremia pod''ema respiratornykh zabolevanii v 1990 g.

Prophylactic properties of a new chemical drug, arbidol, against acute respiratory diseases (ARD) were studied. Arbidol given daily in a dose of 0.2 g for 19 days reduced the morbidity rate 2.3-fold in adults during an outbreak of ARD. Geometric mean titres of antibodies to respiratory viruses among healthy persons did not change after treatment with arbidol indicating the lack of immunosuppressive properties in the drug. The prophylactic effect of arbidol may be due to both specific effect of the drug on influenza and parainfluenza viruses, and its interferon-inducing and immunity-stimulating properties.

Evaluation in children of cold-adapted influenza B live attenuated intranasal vaccine prepared by reassortment between wild-type B/Ann Arbor/1/86 and cold-adapted B/Leningrad/14/55 viruses.

A reassortant cold-adapted (ca) influenza B experimental live attenuated intranasal vaccine was evaluated for safety and immunogenicity in children by means of a blind, placebo controlled study. The vaccine contained the haemagglutinin and neuraminidase genes, and the gene for its non-structural proteins from wild-type (wt) B/Ann Arbor/1/86 virus, the contemporary strain at the time of the study. Other genes were derived from ca B/Leningrad/14/55 virus. No increase in illness rates was seen in the children from ages 3-15 years given vaccine at maximum potency (a one in two dilution of infectious allantoic fluid, having a titre of 10(7.0) EID50) compared to children given placebo. About 60% of seronegative children, ages 3-7 years, exhibited a detectible antibody response following one dose of intranasal vaccine, with the seroresponse rate rising to greater than 70% after two doses of vaccine. Immunogenicity was lowest in seropositive children age 8-15 years, reaching a maximum of 36% after two doses. Results indicated that the vaccine was highly attenuated, and probably of adequate immunogenicity for kindergarten age children. The lower immunogenicity in older children suggests the vaccine might be overly attenuated for use in school-age children who are more likely to have a history of prior natural infection with influenza B virus. Further clinical and epidemiological studies of protection are needed to fully assess this.

[Attenuated recombinant influenza type B virus obtained during crossing of virus B/Ann Arbor/2/86 with the cold-adapted strain B/Leningrad/14/17/55]. / Attenuirovannyi rekombinant virusa grippa tipa B, poluchennyi pri skreshchivanii virusa B/énn arbor/2/86 s kholodoadaptirovannym shtammom B/Leningrad/14/17/55.

Crossing the cold-adapted B/Leningrad/14/17/55 strain with the temperature-sensitive virulent B/Ann Arbor/2/86 strain yielded a recombinant B/14/5/1 which, by the antigenic specificity of hemagglutinin and neuraminidase, corresponded to the B/Ann Arbor/2/86 strain but, like the attenuated donor, had the cold-adapter characteristics. The B/14/5/1 recombinant inherited the genes coding for proteins PB2, PB1, PA, NP, and M from the attenuated master strain and the genes coding for hemagglutinin, neuraminidase, and proteins NS from the virulent master strain. This strain was nonreactive for adults and for children with the initial anti-hemagglutinin antibody titre less than or equal to 1:20 (the reactogenic index being 1 and 0.9% respectively) and was moderately antigenic inducing a 4-fold or more rise of anti-hemagglutinins in the blood of 48.8% of seronegative adults and in 46.6% of seronegative children of 3 to 15 years of age. The highest indices of seroconversions (60%) were recorded in a group of preschool children.

Class-specific antibody responses in school children vaccinated with an A/Brazil/11/78 (H1N1)-like recombinant influenza virus prepared from the A/Leningrad/134/57 paediatric cold-adapted donor strain.

Forty-three school children from 8 to 11 years old were vaccinated intranasally with two doses of a paediatric attenuated influenza vaccine developed by reassortment between cold-adapted A/Leningrad/134/57(H2N2) and an A/Brazil/11/78(H1N1)-like strain. Two vaccine doses were administered 1 month apart in a randomized, blind, placebo-controlled study. Although the first vaccine dose had a low infectivity titre, overall 65% of children who received two doses of vaccine showed serological evidence of infection by HI tests. Serum IgA antibody responses against the vaccine strain were detected in nearly 50% of the vaccines and serum IgG antibody responses were detected in approximately equal to 40% by an enzyme immunoassay.

[Effectiveness of annual booster inoculations against various influenza serotypes and the procedure for mass vaccination]. / Izuchenie éffektivnosti ezhegodnykh, povtornykh privivok protiv grippa raznykh serotipov i taktika massovoi vaktsinatsii.

The epidemiological observation during an outbreak of A (H3N2) influenza in February-March, 1983, showed that the third annual vaccination with killed influenza vaccine did not enhance the effectiveness of vaccinations in the populations under study. It was observed that 14 months after immunization, 55.9% of the subjects examined had antibody titres of 1:40 or higher to the A/Bangkok/1/79 strain antigenically related to the vaccine strain, and 41% of the subjects of this group had antibodies to the subsequent drift variant of influenza A (H3N2) virus. These values were significantly higher than those in the group of subjects given no influenza vaccine. It is suggested that after 2 years of vaccination with killed influenza vaccines with the maximum coverage of the entire population, vaccinations be given alternately to half of previously vaccinated subjects with a 2-year interval up to the emergence of a new shift variant of influenza A virus, when again vaccination of the entire population for two successive years will be required.

[Immunity of the populations of the USSR and East Germany to reference strains of influenza viruses and the characteristics of a new antigenic variant of the virus]. / Izuchenie immuniteta u naseleniia SSSR i GDR k étalonnym shtammam virusov grippa i kharakteristika novogo antigennogo varianta virusa.

In 1985, a new epidemic variant of influenza virus, A/Berlin/6/85 (H3N2) was isolated which differed antigenically from the reference A/Philippines/2/82 virus. The results of the study of population immunity in adults and children of the USSR and GDR to these virus variants confirm the data on the continuing drift of virus A (H3N2).

[Immunomodulating action of levamisole in its combined use with influenza vaccines]. / Immunomoduliruiushchee deistvie levamizola pri ego sochetannom primenenii s grippoznymi vaktsinami.

The immunomodulatory effect of levamisole used in combination with influenza vaccines was studied in young and senile subjects. Levamisole activated antibody production in young subjects in response to administration of a live influenza A (H3N2) vaccine and enhanced the protective effect of vaccinations. The senile subjects vaccinated with inactivated influenza A vaccine (H3N2 and H1N1) had a good immune response and the use of levamisole was not reflected in antibody rises. At the same time, levamisole alone stimulated antibody production to influenza A and B viruses which might be due to irritation of immunocompetent cells carrying "immunological memory".

[Genetic variability of the human influenza virus during adaptation in mice]. / Geneticheskaia izmenchivost' virusa grippa cheloveka v protsesse adaptatsii k mysham.

After 12 passages of a mouse-nonpathogenic influenza A/USSR/90/77 virus in mouse lungs a pathogenic virus was obtained causing death of the animals at 4-7 days after intranasal inoculation. The genetic and structural analysis of the initial and pathogenic viruses performed by oligonucleotide mapping of individual virus genes demonstrated that in the course of adaptation to mice structural changes had occurred at least in 5 out of 8 genes of virus with the exception of the genes coding for matrix and nonstructural proteins. The greatest differences were found in the genes coding for surface glycoproteins: hemagglutinin and neuraminidase. The experimental results indicate an important functional role of surface glycoproteins of influenza virus, particularly hemagglutinin, in the process of adaptation and formation of the pathogenic properties of virus.

Results of a two-year study of humoral immunity to influenza A and B viruses in children under the age of 14 years in Moscow and its suburbs.

A serological survey of antibodies to influenza A(H1N1), A(H2N2), A(H3N2) and B viruses was done with sera collected in Moscow in October 1980 and November 1981 from 542 children under 14 years of age. The results of the study showed convincingly that influenza A(H2N2) viruses were not circulating in Moscow in 1980-81. Low titres found in the sera from four young children were due to cross-reactions which were eliminated from the sera by absorption with A/USSR/174/79(H3N2) virus. Low-level HI titres with A(H0N1) virus in 11 sera were not confirmed by single radial haemolysis (SRH).Serological data showed that A(H3N2) viruses were the main cause of acute respiratory disease in children in July-September 1980 and July-September 1981. These illnesses occurred at the end of the influenza A(H3N2) epidemic of 1979-80 in the third quarter of 1980. The influenza A(H3N2) virus circulated in Moscow during December 1981 and January 1982, but influenza did not reach epidemic levels. A low proportion (10%) of children with antibodies to influenza B virus at titres of 1:40 or higher in 1980 indicated the possibility of an epidemic due to this virus in Moscow in 1980-81. Such an epidemic did occur in December 1980 and January 1981.

[Humoral immunity to influenza A and B viruses in the blood sera of children younger than 14 in 1981]. / Gumoral'nyi immunitet k virusam grippa A i B v syvorotakh krovi detei molozhe 14 let v 1981 g.

Blood sera from 317 children with the history of noninfectious diseases or normal children pretreated with RDE were collected and examined for antihemagglutinins to 7 influenza virus strains in order to check the results of studies of 1980 and to study the immunity status to influenza A (H1N1), A (H2N2), A (H3N2) and B in the preepidemic period of 1981. Negative results of antihemagglutinin detection to influenza A/Iksha/1/57 (H2N2) in sera of all the children have confirmed the conclusion made in the previous paper (1) that influenza A (H1N2) viruses have not circulated in recent years among the population of Moscow City and suburban areas. Fourteen sera positive in HI tests with A/Shklyawer/49 virus similar to A/PR/8/34 (H1N1) in titres from 1:20 to 1:40 did not produce hemolysis zones with A/PR/8/34 virus in RHT, but most of these sera gave similar results of both tests with A/Brazil/11/79 and A/Khabarovsk/1/77 viruses. This attests to cross, nonspecific nature of hemagglutination-inhibition with A/Shklyawer/49 virus which evidently does not circulate now in the population of Moscow City and suburbs. An increase in the level of immunity to influenza B and A (H1N1)/1977 viruses reflected the epidemic situation of the previous year.

[Trial of polyguacyl safety and tolerance]. / Ispytanie bezvrednosti i perenosimosti poliguatsila.

The results of studies of the antiviral and interferon-inducing activity of the synthetic interferon inducer polyguacyl in white mice as well as the results of the study of safety and tolerance of this drug given to human subjects as aerosol and intranasally are presented. Both modes of administration to mice induced production of endogenous interferon, although after intranasal inoculation high interferon titres in the blood serum of the animals were observed for longer periods of time, whereas after aerosol administration interferon disappeared more rapidly. Significant antiviral protection was achieved only by the intranasal administration of the inducer resulting in 84.0% survival of the animals challenged with the mouse-adapted influenza A/Aichi virus. Clinical trials of polyguacyl in human volunteers demonstrated the safety and good tolerance of this drug given both as aerosol and intranasally.