The reactogenicity and safety of a multicomponent vaccine (VP-4) in the prevention of acute respiratory diseases in preschoolers

The reactogenicity and safety of poly-component vaccine (VP-4), prepared from the antigens of opportunistic bacteria, in the prophylaxis of acute respiratory diseases (ARD) in children aged 2.6-6 years. The vaccine was administered intranasally in 3 administrations and orally in 6-8 administrations at intervals of 3-4 days for a period of 24 +/- 4 days. The prophylaxis of ARD with the use of VP-4 was carried out in 168 children in 4 children's preschool institutions. The control group was made up of 120 children, attending the same institutions. The study revealed that VP-4 had low reactogenicity and induced short-time systemic and local reactions (common cold, cough). The administration of VP-4 at a period of the epidemic rise on influenza and ARD morbidity did not lead to an increase in the frequency and duration of ARD in the vaccinees, as well as to the exacerbation of chronic infection and the allergization of the body.     

Immunoprophylaxis of acute respiratory diseases with bacterial multicomponent vaccine VP-4 in children at preschool institutions

The prophylactic action of polycomponent vaccine B[symbol: see text]-4, prepared from the antigens of opportunistic bacteria, on morbidity rate in acute respiratory diseases (ARD) of bacterial and mixed (bacterial and viral) etiology in 121 children aged 2-5 years, attending pre-school institutions was evaluated. For comparison, a group of 118 children of the same age from the same institutions was formed. The vaccine was introduced after the schedule consisting of 3 intranasal and 6-9 oral administrations made at intervals of 3-4 days. The duration of the course of immunization was 26 +/- 4 days. The prophylactic effect of B[symbol: see text]-4 on ARD morbidity was evaluated by the number of ARD cases and their duration per child. The prophylactic effect of B[symbol: see text]-4 on ARD morbidity lasted 14 months (the term of observation) after immunization and was manifested by a decrease in the number and duration of ARD cases after administration of the preparation, also in a group of highly susceptible children.     

Immunostimulating activity of polycomponent vaccine "Immunovac-VP-4" and grippol after their combined administration

The experimental study of the immunostimulating activity of therapeutic bacterial polycomponent vaccine VP-4 and prophylactic vaccine grippol, introduced both separately and in combination, on mice infected with Salmonella typhimurium, used as a model. Both preparations were found to produce an immunomodulating effect. The combined subcutaneous injection of VP-4 and grippol did not decrease their immunostimulating activity, but their separate administration at an interval of 14 days resulted in essential decrease in the protective activity of each of these two preparations. As shown on the model of Klebsiella infection in mice, challenged 4 weeks after immunization, VP-4 ensured the survival of 78.6% of mice, while after the injection of grippol their survival rate was not different from that of the group of intact animals. The evaluation of the immunostimulating activity of these preparations under the conditions of the prophylaxis of influenza and acute respiratory infections in organized groups of children revealed that the use of VP-4 alone or grippol in combination with VP-4 considerably decreased the number of secondary bacterial complications in children.     

Invasive pneumococcal disease in Portugal prior to and after the introduction of pneumococcal heptavalent conjugate vaccine

The rates of invasive pneumococcal disease (IPD), serotype distribution and antimicrobial susceptibility prior to and after the introduction of the heptavalent pneumococcal conjugate vaccine in Portuguese children were evaluated. The changes in incidence of IPD in children under 1 year old between the two periods of the study was not significant (P=0.53), despite the 21% decline. In children under 18 years old there was a 27.7% decrease in vaccine serotypes. All nonvaccine serotypes increased 71.4%. The decrease in vaccine serotypes was more impressive during the first year of life (-54.8%) than for children between 1 and 5 years of age (-19.1%). Among children under 1 year old, penicillin nonsusceptible isolates declined between the two periods of the study (47.2% vs. 25.0%) (P=0.03), as did those of cefotaxime and ceftriaxone nonsusceptible isolates. No changes were observed for isolates nonsusceptible to tetracycline and macrolides. The serotypes of these nonsusceptible isolates differed after the introduction of vaccine (P=0.01). Multiresistance increased 57.1% after the introduction of vaccine. Multiresistant isolates with vaccine serotype declined 42.9% (P<0.001), and nonvaccine serotypes appeared during the vaccination period (P<0.001). These findings suggest a replacement of vaccine serotypes by nonvaccine serotypes, mainly among nonsusceptible isolates.     

Assessment of effect of vaccination against pneumococcal infection in children with chronic renal failure and glomerulonephritis

Clinical effect and immune response to vaccination with PNEUMO 23 vaccine was assessed in 18 children with chronic renal failure (CRF) and 40 children with different forms of glomerulonephritis (GN) aged 2 - 15 years. Control group was comprised by nonvaccinated patients (16 patients with CRF; 20 -with GN). Children from two groups were comparable on age and severity of disease's course. Local adverse reactions with duration not longer than 2 days were registered in 22% of vaccinees with CRF, and in 20% of vaccinees with GN. Mild and moderate systemic reactions were registered in 11% and 7.5% of recipients respectively. 1 month after vaccination significant 2.5 - 3.2-fold increase of antibodies concentration was detected in all groups irrespective from nosology and previous treatment. Two-fold increase of concentration of antibodies was observed in 64% and 61% of children with GN and CRF respectively. Clinical effect of vaccination appeared as 2.9-fold decrease of acute respiratory disease (ARD) incidence. Demand in antibacterial therapy decreased by 6.4-fold. Duration of ARD and course of antibacterial treatment decreased by 2.2 and 3 times respectively. Proportion of GN exacerbations related to infecvion decreased from 39% before vaccination to 8% after vaccination. In the control group this proportion did not change (50% and 45% respectively). Vaccine efficacy index was 2.13, coefficient of efficacy - 53.1%.     

Humoral imunity to pertussis in children with diabetes of type 1

To determine the state of humoral immunity to pertussis in children with insulin-dependent diabetes, IgG antibodies to pertussis toxin (PT) were determined in blood serum samples by means of EIA. In a group of children aged up to 6 years the highest percentage (100%) received the complete course of vaccination against pertussis with Russian adsorbed DPT vaccine, containing whole-cell pertussis monovaccine, while in a group over 6 years the complete vaccination course (3 vaccinations and 1 revaccination) had 53.4% of children. Pertussis morbidity was considerably higher in nonvaccinated subjects than in children with 4-fold vaccination (p < 0.001). The coefficient of association (Q) was 0.84. Children of all age groups were found to have low and average titers of antibodies to PT. The regressive analysis showed a decrease in antibodies in persons completely immunized against pertussis by the age of 6 years old. The presence of antibodies in nonimmunized persons showed that cases of pertussis or carrier state took place among the population. High titers of antibodies, indicative of recent cases of pertussis, were registered in all age groups, but high titers of antibodies were registered mostly in the group of children over 13 years old (p < 0.05), which confirmed an increase in pertussis morbidity in adolescents. Thus, vaccination against pertussis effectively protected children with diabetes of type 1, aged up to 6 years. For more prolonged protection the vaccination and revaccination of children aged over 4 years old is necessary.     

Epidemic process of pertussis in Moscow

Materials reflecting the dynamics of pertussis morbidity during the period of 1958 - 2003 under the conditions of prolonged mass immunization of the child population with adsorbed DPT vaccine are presented. The planned vaccination of children led to the decrease of pertussis morbidity during the first 10 years, but groundless abstentions from vaccination during the 1980s - 1990s contributed to a sharp rise in morbidity among children of younger age groups. During the recent four years a rise in pertussis morbidity was registered in 2000 (71.79 per 100,000 of the population), followed by the most significant for the last 20 years drop in morbidity in 2002--down to 9.89. But in 2003 the growth of morbidity was again registered (38.67). Recently periodic rises and drops in morbidity occurred simultaneously with the increased coverage of children of younger age groups with vaccination. In recent years changes in the age structure of patients were observed: the specific proportion of school children increased (in 2003 morbidity rates in children aged 6 - 10 years were 288.6 - 270.7), simultaneously high morbidity among children aged up to one year (274.9) was registered. The specific proportion of pertussis-affected children aged above 7 years reached 65%. From the late 1990s until present in 87.1% of cases strains of serotype 1.0.3 prevailed in the population of B. pertussis strains. But in recent years the circulation of strains 1.2.3, spread in the prevaccination period and having toxicity similar to that of strains of serotype 1.0.3, while exceeding them in virulence, in sufficiently high proportion (7.0% in 2002) was noted. This was indicative of the possibility of the unfavorable development of the epidemic process of pertussis infection.     

Naso-subcutaneous application of the polycomponent vaccine VP-4 for the treatment of patients with bronchial asthma and chronic obstructive bronchitis

Bacterial polycomponent vaccine (VP-4) earlier developed at the Mechnikov Research Institute for Vaccines and Sera on the basis of antigenic complexes of Klebsiella pneumoniae, Proteus vulgaris, Escherichia coli, Staphylococcus aureus was used within the program of clinical trials, for the treatment of 30 patients aged 16-59 years with the atopic and mixed form of bronchial asthma and chronic obstructive bronchitis by the combined naso-subcutaneous application. A good therapeutic effect produced by the vaccine was registered in 83.3% of the patients. It was manifested by a lower frequency of acute respiratory diseases and bronchopulmonary diseases as well as decreased need in antibiotic therapy. In the group of comparison a good effect was noted in 40% of the patients during 6 months of observation (statistically significant difference). Side effects caused by the administration of the vaccine were transitory, had mainly local character and disappeared without any treatment. In 1 patient the development of anaphylactic shock was observed. The positive effect of vaccine VP-4 could be attributed to the improved indices of cell-mediated immunity, an increased synthesis of alpha- and gamma-interferon, a droped level of IgE and specific IgG antibodies to Staphylococcus sp., Klebsiella sp., Proteus sp., Escherichia coli.     

Approaches to prevention and treatment of latex allergy

Data on sensitization to latex as well as measures aimed at prevention and treatment of latex allergy, are presented. The intensity of the symptoms manifestation of latex allergy was shown to depend on the duration of contact with latex. To prevent the development of latex allergy, the following preparations were used: the antihistaminic preparation Claritine, the immunocorrecting preparations Ruzam and polycomponent vaccine VP-4. The use of Claritine was shown to lead to the alleviation of the symptoms of latex allergy, but after treatment with Claritine was stopped the symptoms of latex allergy reappeared. The clinical effect lasted for as long as 2 months after treatment with Ruzam, while in case of polycomponent vaccine VP-4 use remission was registered even 3 months later. The data presented thus confirm topicality of the latex allergy problem and practical importance of using the immunocorrecting preparations Ruzam and polycomponent vaccine VP-4 for its prevention and treatment.     

Measles morbidity among children inoculated against this infection

In the serological survey of 2009 children immunized against measles 285 children (14.2%) were found to be seronegative to this infection in the hemagglutination inhibition test with 4 hemagglutinating units of the antigen. Among 1724 immunized children showing positive response to vaccination and placed under dynamic observation for 11 years, 2 cases of measles were registered. At the same time, in the dynamic observation of 111 seronegative children 66 measles cases (59.5%) were registered during the above period, while among 169 children, also seronegative, but receiving booster immunization against measles, morbidity rate was only 1.2%. In some vaccinees the decrease of postvaccinal immunity to seronegative values was observed, but such decrease had no essential influence on the morbidity level among the vaccines. The increase of measles morbidity among schoolchildren immunized against this infection was due not to the decrease of their postvaccinal immunity, but to their concentration in schools and to their more intensive contacts with the sources of infection in comparison with children of preschool age.     

Protective efficacy of combined administration of the multicomponent vaccine and the immunomodulator myelopid in experimental infections in mice

The influence of myelopid (MP) on the protective activity of polycomponent vaccine VP-4 prepared from the antigens of opportunistic bacteria was studied on experimental infections of mice, caused by Klebsiella pneumoniae, Salmonella typhimurium and Staphylococcus aureus. In staphylococcal and Klebsiella infections the joint administration of vaccine VP-4 and MP produced more pronounced protective effect than each of these preparations, introduced alone. The protective action of vaccine VP-4 was specially enforced by MP in cases of local staphylococcal infection. Recommendations on the joint use of two or more immunomodulating agents are possible only on the basis of the experimental substantiation of their effect in definite infections.     

Dynamics of autoantibodies in elderly persons in the process of vaccination with Grippol and multicomponent vaccine VP-4

The dynamics of antibodies to organ specific and organ nonspecific antigens in the process of combined immunization with Grippol, an influenza polymer subunit vaccine and polycomponent vaccine VP-4 used for prophylaxis of acute respiratory infections, was under study. Persons aged 65 years and older were vaccinated. Grippol alone was introduced in a single subcutaneous injection into 92 persons and Grippol in combination with vaccine VP-4--to 103 persons. B[symbol: see text]-4 Vaccine was introduced intranasally and orally (6-8 doses). The administration of vaccine VP-4 was started simultaneously with vaccination with Grippol. Prior to immunization and 1 and 5 months later autoantibodies to the following antigens were detected: DNA (native and denaturated), collagen, elastin, myelin basic protein, microsomal fractions of kidneys, lungs, heart, liver, intestine, pituitary body, thyroid gland, pancreas, adrenal glands, ovaries, mucous and muscular layers of stomach. The number of persons with the level of antibodies at least to one of the antigens under study exceeding the normal values prior to vaccination varied from 19.4 +/- 8.6% to 41.5 +/- 7.7%, the average values of positive sera being 0.26 +/- 0.05 to 0.32 +/- 0.08 delta OD. One and 5 months after vaccination both values varied within the same limits in both groups. Immunization with Grippol as well as with its combination with vaccine VP-4 was found to increased spectrum of antibodies to tissue antigens and their increased content. The data give evidence that Grippol and vaccine Vp-4, introduced according to the immunization schedule used in these experiments, do not induce development of autoimmune processes.     

Effect of Pneumococcal Conjugate Vaccination in Uruguay,a Middle-Income Country

Background

In 2008, a 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the routine childhood immunization program in Uruguay, with a 2+1 schedule. In 2010, PCV13 replaced PCV7, and the same 2+1 schedule was used. The effect of these pneumococcal vaccines on the incidence of invasive pneumococcal infections (IPD) and on serotype distribution was analyzed retrospectively, based on passive national laboratory surveillance.

Methods

Data from 1,887 IPD isolates from 5 years before and 5 years after PCV7 introduction (7 before and 3 after PCV13 introduction) was examined to assess the incidence rate per 100,000 age-specific population of all IPD, PCV7-serotypes, and PCV13-serotypes associated IPD among children <2 years and 2 to 4 years old, and patients ≥5 years old. Trends of frequency for each serotype were also analyzed.

Results

Comparison of pre-vaccination (2003–2007) and post-vaccination (2008–2012) periods showed a significant decrease in IPD incidence among children <2 years old (IR 68.7 to IR 29.6, p<0.001) and children 2 to 4 years (p<0.04). IPD caused by serotypes in PCV7 was reduced by 95.6% and IPD caused by 6 serotypes added in PCV13 was reduced by 83.9% in children <5 years old. Indirect effects of both conjugate vaccines were observed among patients ≥5 years old one year after the introduction of each vaccine, in 2010 for PCV7 and in 2012 for PCV13. Nevertheless, for reasons that still need to be explained, perhaps due to ascertainment bias, total IPD in this group increased after 2007. In 2012, the relative frequency of vaccine serotypes among vaccinated and unvaccinated population declined, except for serotype 3. Non vaccine serotypes with increasing frequency were identified, in rank order: 12F, 8, 24F, 22F, 24A, 15C, 9N, 10A and 33.

Conclusion

Consecutive immunization with PCV7 and PCV13 has significantly reduced IPD in children <5 years of age in Uruguay.     

The efficacy of exogenous and endogenous interferonization in preventing influenza]

In this work the results of using interferon (IFN), Dibasol and the combination of these preparations for the urgent prophylaxis of influenza and acute respiratory diseases (ARD) among the employees of the Gamaleia Research Institute of Epidemiology and Microbiology (USSR Acad. Med. Sci.) are summarized. Reaferon and Dibasol decrease ARD morbidity 2 times and leukocytic IFN decreases it 1.4 times, while the combined administration of Dibasol and IFN has proved to be ineffective. Reaferon is mainly a prophylactic remedy; it has been found to bring about almost no decrease in the number of patients at the peak of morbidity, while pronouncedly decreasing it in two weeks after the administration of the preparation. Dibasol has a curative effect, sharply interrupting the beginning rise of morbidity. Reaferon normalizes the characteristics of the IFN status, decreasing the amount of circulating IFN and enhancing the capacity of leukocytes for producing alpha-IFN and gamma-IFN. For the prophylaxis of respiratory infections the use of Reaferon is advisable 3-4 weeks prior to the beginning of the epidemic and then, when the first cases of infection are registered, the course of prophylaxis with Dibasol should be carried out.     

Multicomponent vaccine VP-4 in the therapy of allergic diseases

In the present study the results of the polycomponent vaccine B[symbol: see text]-4 use for the therapy of patients with bronchial asthma (BA) and latex allergy were generalized. The vaccine was introduced by the nasal-subcutaneous or nasal-oral administration simultaneously with the basic therapy. Te studies were conducted first on limited groups of patients, then in the course of the State Trial with the use of placebo control. Excellent and good effect lasting for 1 year and over was registered in 36 patients (66.7%) out of 54 BA patients receiving the vaccine by the intranasal-subcutaneous method. Immunotherapy produced no positive effect in 13 patients (24.1%). Out of 35 examined patients receiving the vaccine by the intranasal oral method, excellent and good effect was registered in 26 patients (74.2%). No effect was registered in 4 patients (11.4%). In the group of 28 patients receiving placebo simultaneously with the basic therapy positive dynamics in the course of the disease was observed only in 3 patients. Treatment with polycomponent vaccine B[symbol: see text]-4 led to a prolonged (to a year and more) decrease in the frequency and severity of exacerbations, contributed to the prolongation of remissions and to a decrease in the amount of administered medicinal preparations, especially systemic corticosteroids. Immunotherapy ensured the correction of the content of lymphocyte subpopulations with markers CD3, CD4, CD72 and a rise in the titers of antibodies to antigens contained in the preparation. The use of therapeutic polycomponent vaccine B[symbol: see text]-4 for the treatment of patients with latex allergy ensured the state of prolonged remission in this group of patients. On the basis of our investigations we believe that the use of the therapeutic polycomponent vaccine B[symbol: see text]-4 may be included into the basis therapy of allergic diseases.     

The use of influenza vaccines and remantadine for protection against influenza in industrial enterprises

The effectiveness of inactivated and live influenza vaccines and remantidin was studied in persons with different annual morbidity rate in influenza and acute respiratory diseases (ARD). After three and more years of immunization with the inactivated vaccine the number of seroconversions to viruses A (H1N1) and A (H3N2) in vaccinees decreased, respectively, from 75.0 to 26.0% and from 79.3 to 38.8%, and after an interval of two years or the alternation of inactivated and live vaccines the number of seroconversions increased to 57.9-64.0%. The significant decrease of morbidity rate in influenza and ARD were observed only in persons, having had frequent ARD in their medical history and immunized with live and inactivated vaccines simultaneously or separately with the alternation of these vaccines every year (the effectiveness index being equal to 1.7-1.8). At the period of epidemic the controlled administration of remantadin to persons with contraindications to immunization ensured the decrease of morbidity rate in influenza 1.5-1.8 times; in vaccinees, highly susceptible to ARD, the administration of remantadin decreased morbidity rate 2.3 times.     

The control of viral diseases in the developing countries with the use of existing vaccines]

In developing countries, every year about 70 million measles cases occur with 1.5 million deaths, over 200,000 children contract paralytic poliomyelitis, 50 million people get infected with viral B hepatitis causing over 1 million deaths, and several thousand people perish because of yellow fever according to WHO data. At the present time, there are 12 vaccines against viruses: vaccines against German measles and mumps in addition to the above. The universal immunization program (UIP) of WHO targets measles and polio. In 1989, a WHO resolution envisioned a 90% immunization coverage by the year 2000. Measles vaccination is recommended for children aged 9-23 months, since most children have maternal antibodies during the first 3-13 months of age. The Edmonston-Zagreb vaccine provided seroconversion of 92, 96, and 98% for 18 months vs. the 66, 76, and 91% rate of the Schwarz vaccine. In the US, measles incidence increased from 1497 cases in 1983 to 6382 cases in 1988 to over 14,000 cases in 1989, prompting second vaccination in children of school age. The highest incidence of polio was registered in Southeast Asia, although it declined from 1 case/100,000 population in 1975 to .5/100,000 in 1988. Oral poliomyelitis vaccine (OPV) provides protection: there is only 1 case/2.5 million vaccinations. Hepatitis B has infected over 2 billion people. About 300 million are carriers, with a prevalence of 20% in African, Asian, and Pacific region populations. Plasmatic and bioengineered recombinant vaccine type have been used in 30 million people. The first dose is given postnatally, the second at 1-2 months of age, and the 3rd at 1 year of age. Yellow fever vaccine was 50 years old in 1988, yet during 1986-1988 there were 5395 cases with 3172 deaths in Africa and South America. Vaccination provides 90-95% seroconversion, and periodic follow-up vaccinations under UIP could eradicate these infections and their etiologic agents.     

Etiology of influenza according to the data of serological diagnostics in hospital patients in St. Petersburg at the period of 1968 - 2000

The specific features of the etiology of influenza in children and adults at the period of the simultaneous circulation of two subtypes of influenza virus A, according to the results in the hemagglutination-inhibition reaction in 261,490 influenza and ARD patients hospitalized in St. Petersburg in the course of 32 years, were analyzed. The results of serological diagnostics was shown to correspond to the data of the identification of influenza viruses in Russia and all over the world. At the period of epidemics diseases caused by the main infective agents of the epidemics were detected in 11.0% - 51.0% of cases and by concomitant infective agents, in 0.6% - 12.4% of cases. After the reappearance of influenza virus A(H1N1) in circulation higher frequency of mixed forms of infection and the presence of competition between the subtypes of influenza virus A was noted. In young children a decrease in differences in the proportion of influenza cases, caused by the main and concomitant infective agents, as well as between the detection of influenza in epidemic and in summer periods, was registered.     

Clinical and immunological effect produced by vaccination with "Pneumo 23" of children with atopic bronchial asthma

A total of 45 children aged 4-16 years with atopic bronchial asthma of different severity level-resulted from a past case of outhospital pneumonia, received vaccine "Pneumo 23" ("Aventis Pasteur", France). The vaccine was found to be well tolerated, no cases of the exacerbation of the atopic process were registered. A reliable Increased level of specific antibodies to the mixture of polysaccharides, contained in the vaccine "Pneumo 23", was found to occur. The tendency towards decreased level of serum IgE was established.     

Immunovac-VP-4, immunomodulator decreases immunosuppression and enhances the cytotoxic activity induced by the cytostatic Cisplatin

The influence of the vaccine Immunovac-VP-4, prepared from the antigens of opportunistic microorganisms, on the proliferative and cytotoxic activity on peripheral blood mononuclears (PBMN) from healthy donors in vitro and on spleen cells of CBA mice in vivo during their incubation with Cisplatin was studied. VP-4 produced a dose-dependent, stimulating effect on the proliferative potential of PBMN and, when used in the highest of all tested doses (20 microg/ml), increased the Cisplatin-suppressed proliferative activity of PBMN in 9.4-fold. VP-4 increased the cytotoxic activity of PBMN on tumor line cells K-562 (38,4 to 60.1%) and increased the cytotoxic effect of Cisplatin (68.18 to 87.56%). A single injection of VP-4 to mice stimulated the proliferative activity of spleen cells, studied ex vivo, units and partially restored their cytostatic-suppressed activity. The cytotoxic action of the spleen cells of immunized mice on tumor line cells YAC-1 was twice as great as that of spleen cells taken from intact animals and potentiated the cytotoxic action of Cisplatin. The mechanism of increasing the proliferative activity and cytotoxic effect of monomuclears under the influence of vaccine VP-4 is seemingly linked with the synthesis of cytokines, influencing the lymphokine-activated cytotoxicity of lymphocytes.