Search

Background: The field efficacy of a bivalent vaccine containing porcine circovirus type 2b (PCV2b) and Mycoplasma hyopneumoniae was evaluated on three pig farms., Methods: Three pig farms were used, two of which had a history of subclinical PCV2 and clinical M. hyopneumoniae infections between 84 and 126 days of age while concurrent porcine circovirus-associated disease and clinical M. hyopneumoniae infection between 70 and 105 days of age. Each farm vaccinated pigs with a single dose of a bivalent vaccine at 10 days of age while unvaccinated pigs were administered a single dose of phosphate buffered-saline at the same age., Results: Vaccination improved growth performance and reduced clinical scores significantly (p < .05) when compared with unvaccinated animals. The amount of PCV2d loads in blood and M. hyopneumoniae loads in nasal swabs of vaccinated animals were also significantly lower (p < .05) when compared with unvaccinated animals. Immunologically, vaccinated groups elicited a significantly higher (p < .05) level of protective immunity against PCV2d such as neutralizing antibodies and interferon-γ secreting cells (IFN-γ-SC), as well as protective immunity against M. hyopneumoniae such as IFN-γ-SC when compared with unvaccinated animals. Pathologically, vaccination significantly lowered (p < .05) the scores of M. hyopneumoniae-induced pneumonia and PCV2-associated lymphoid lesions when compared with unvaccinated animals., Conclusions: The evaluated bivalent vaccine provided good protection against PCV2d and M. hyopneumoniae infection under field conditions., (© 2020 The Authors Veterinary Medicine and Science Published by John Wiley & Sons Ltd.)

Although effective vaccines have been developed against the common Leptospira serovars, they are still reported in clinical cases, while others are increasingly prevalent. The results from four challenge studies following vaccination of dogs with a new combination vaccine (DHPPi/L4R) containing inactivated L. serovars, L. canicola, L. icterohaemorrhagiae, L. bratislava and L. grippotyphosa conducted to satisfy the requirements of the European Pharmacopoeia monograph (01/2008:0447), are reported. Six week old dogs received two vaccinations, three weeks apart, and were challenged 25 days later with different isolates of the L. serovars. Clinical observations were recorded, and blood, urine and tissue samples were collected for analysis. Following challenge, non-vaccinated dogs demonstrated various clinical signs, while no vaccinated dogs were affected; significant differences in mean clinical scores were observed. Measurable antibody titres to each Leptospira antigen were seen in vaccinated dogs 21 days following the first vaccination, with further increases in antibody titres observed following challenge with the respective Leptospira strain. Non-vaccinated dogs remained seronegative until challenge. Leptospira were re-isolated from the blood, urine, kidney and liver of all non-vaccinated dogs following challenge. In contrast no vaccinated dogs had Leptospira re-isolated from the same tissues. Significant differences were seen in number of days with positive isolation (blood and urine) and in number of dogs with positive samples (kidney and liver). In conclusion, vaccination of dogs with the new vaccine induces protective immunity 25 days after second vaccination with protection against infection, renal infection and clinical signs following challenge., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Aim: Proof of therapeutic efficacy of a novel type of vaccine with a combination of natural Toll like receptor agonists (TLR) 1/2, 4, 5/6, 9 in infectious and noninfectious human pathology., Materials and Methods: Immunovac-VP-4 vaccine, containing antigens of opportunistic microorganisms that are TLR 1/2, 4, 5/6, 9 ligands, was used for experiments and clinical trials., Results: Immunovac-VP-4 activates innate immunity by inducing maturation of dendritic cells with expression of costimulating molecules on their membrane (CD40+, CD80+, CD86+), terminal differentiation molecules--CD83+ and antigen-presenting molecules (MHC class I and II); activates proinflammatory (TNFalpha, IL-6) and regulatory (IL-12, INFgamma) cytokine synthesis that programs T-lymphocyte differentiation by Th1 pathway; increases cytotoxic activity of natural killer cells, inhibits melanoma B16 growth and Lewis lung carcinoma metastasis. Therapeutic effect of Immunovac-VP-4 was evident regardless of pathology by a significant decrease of quantity and severity of recidives, improvement of all clinical parameters, reduction of quantity of administered pharmaceutical preparations including antibiotics and glucocorticosteroids. The rate of intercurrent acute respiratory viral illnesses and their bacterial complications decreased. Immunovac-VP-4 therapy modified course of illness from severe into milder forms. Positive therapeutic effect was 69.2 - 100%., Conclusion: High therapeutic effect of vaccine therapy is based on innate immunity activation by combining TLR agonists. Immunovac-VP-4 contains an optimal combination of natural TLR agonists that ensure high therapeutic effect in various nosological forms of infectious and noninfectious human pathology.

Aim: Assessment of therapeutic effect and immunologic parameters during use of Immunovac vaccine for complex treatment of chronic forms of pyoderma., Materials and Methods: Ninety-five patients with different clinical forms of chronic pyoderma (furunculosis, hydradenitis, chronic ulcerative and ulcerative-vegetans pyoderma, folliculitis, impetigo etc.) were studied. Fifty-nine patients received immunotherapy with Immunovac vaccine together with basic therapy and 36 patients comprised control group treated only with basic therapy. Studied immunologic parameters were as follows: assessment of functional activity of lymphocytes, determination of lymphocyte subpopulations by flow cytometry, total immunoglobulins classes A, G, M by radial immunoduffusion, affinity of antibodies by enzyme immunoassay, levels of IFNalpha and IFNgamma., Results: Use of Immunovac vaccine in complex treatment of patients with chronic forms of pyoderma enhanced clinical effect of basic therapy, which expressed in decrease of severity and frequency of disease relapses irrespective to clinical form and severity of pyoderma. Therapeutic effect during use of Immunovac vaccine amounted 84.7%, whereas in control group it was 41.6% after 12 months of follow-up. Increase of functional activity of neutrophils, subpopulation of lymphocytes with markers CD4+, CD8+, CD72+, affinity of antibodies as well as induced production of IFNalpha and IFNgamma was revealed. Correction of immunologic parameters correlated with positive results of patients treatment., Conclusion: Inclusion of bacterial polycomponent vaccine Immunovac in complex treatment of patients with chronic pyoderma promotes enhancement of therapeutic effect of basic therapy and correction of immunologic parameters.

The efficacy of a modified live monovalent Flavobacterium columnare vaccine and bivalent F. columnare and Edwardsiella ictaluri vaccines were evaluated following immersion vaccination of eyed channel catfish (Ictalurus punctatus) eggs. The modified live F. columnare vaccine was grown in modified Shieh broth and administered at 1.35 x 10(7) CFU/ml for 15 min exposure (1l water). Booster immunization was conducted at day 34 with 2.17 x 10(7) CFU/ml for 15 min. Bivalent vaccines consisted of a 1:1 ratio of the modified live F. columnare and AQUAVAC-ESC vaccine for the 15 min exposure (1l immersion bath). Non-vaccinated controls were held in 1l water without vaccine for 15 min. Fish were challenged with F. columnare (ALG-00-530) by immersion at days 109, 116, and 137 post-primary immunization or E. ictaluri (AL-93-75) by immersion at day 116 (bivalent vaccine group). Efficacy of monovalent modified live F. columnare vaccine administered singly or with a booster vaccination was shown to be protective with relative percent survival (RPS) values ranging from 50.0 to 76.8. Some variation was seen in RPS values following bivalent immunization, ranging from 33.0 to 59.7 in the fish challenged with F. columnare and 44.5 to 66.7 in fish challenged with E. ictaluri. However, the RPS values were not statistically different. The results suggest that administration of live bivalent vaccine at the eyed-egg stage is safe and elicits protection upon single pathogen challenge.

Effect of immunomodulators for microbial origin on innate immunity and antitumor system was continued to study. Immunomodificator Immunovac VP-4, purified staphylococcal toxoid and glucosaminyl muramyl dipeptide (GMDP) equally enhanced cytotoxicity of mononuclear leukocytes of peripheral blood of healthy donors. Index of cytotoxicity was 2.78, 2.77 and 2.70 respectively. Reduced metastatic progression of Lewis lung carcinoma in mice was observed after Immunovac VP-4 and GMDP administration. Effectiveness was seen when preparations administered according to schedules including their administration before implantation of the tumor. If preparations were administered number of metastases reduced in 4.4-5.6 times and size of metastases reduced in 7-10 times. Interplay between antitumor activity of studied immunomodulators and cytotoxic activity of NK-cells, which are base effectors of antitumor immune response, are discussed.

IgE-mediated reactions linked with the polarization of the immune process towards, mainly, the activation of Th2 lymphocytes which synthesized interleukins, responsible for switching over B lymphocytes to the production of IgE, were found to be the most important mechanism of the pathogenesis of atopic dermatitis (AD). The use of immunomodulating preparations, capable of changing unbalance in the system of Th1/Th2 cells, is one of promising approaches to the complex therapy of AD. Poly-component vaccine Immunovac BN-4 was included into the complex therapy of AD in children, The dynamics of immunological characteristics was studied for the period of 6 months after the end of the course of therapy. A considerable increase in the absolute and relative amount of lymphocytes with markers CD3, CD4, CD16, CD21, CD25, a rise in the levels of IgA, IgG and a decrease in the level of total IgE in the blood serum were established. The inclusion of the polycomponent vaccine into the complex therapy of AD may be recommended.

An oral polybacterial immunomodulator Urostim (U), composed of killed cells and their lysates from E. coli expressing type 1 and Pili, E. coli Rc mutant, P. mirabilis, K. pneumoniae and E. faecalis was created for immunoprophylaxis and immunotherapy of urinary tract infections (UTIs). In experimental animal models, the stimulating effect of U on lymphocyte functional activity, macrophage phagocytosis and antibody producing cells, was established. In this study the immuno-modulating effects of U on the proliferating capacity and ultrastructural morphologic changes of lymphocytes, cytokine production and specific systemic humoral and mucosal immune responses in patients with UTIs have been evaluated. Patients enrolled in the study, received orally 50 mg U daily for a period of three months. On days 0, 30 and 90 a quantitative analysis was performed on lymphoproliferative responses to polyclonal mitogens, IL-2 and the specific antigen U, the production of specific serum and saliva IgA, IgM and IgG antibodies to all components of U and the concentration of pro-inflammatory cytokines. There was significant improvement of non-specific and specific lymphoproliferative responses on days 30 and 90 after the onset of treatment with U, confirmed by electronmicroscopic studies. The highest concentrations of serum proinflammatory cytokines TNF-alpha, IL-1beta and IL-6 were registered at baseline followed by a decrease until the end of the observation period. This finding correlates with the gradual decrease of immune activation as measured by the spontaneous lymphocyte proliferation. Data from the production of specific antibacterial antibodies in serum and saliva show two types of reactions. The first type was registered in patients with low pre-treatment levels in whom the concentration of specific antibodies increased on days 30 and 90. The second type of reaction was observed in patients with high pre-treatment levels, which dropped on day 30 and were usually followed by an increase at the end of the study. These results provide evidence for the immuno-modulating effect of U. Our data show that the oral administration of the polybacterial immunomodulator Urostim stimulates adequate cellular and humoral systemic and mucosal immune responses in patients with chronic UTIs.

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.

During 20 years different oral immunostimulators have been developed and tested in the National Center of Infectious and Parasitic Diseases in Sofia, Bulgaria. Some of them are widely and quite successfully used in clinical practice for immunotherapy and immunoprophxis (Respivax, Urostim, Dentavax). Data on the immunostimulating activity of polybacterial immunostimulants are presented. Numerous clinical investigations, including double-blind studies, have convincingly demonstrated their high efficacy in the prevention and treatment of non-specific infections of the respiratory organs, the urogenital tract, the oral mucosa and periodontium, as well as in the complex therapy of AIDS. All these facts suggest that immunostimulators, in particular polybacterial ones, are a highly promising tool of modern immunotherapy and immunoprophylaxis aimed at the beneficial modulation of immune response in humans.

Twenty-six pregnant women (group I) with uroinfection were treated with Urostim and antibiotic. The effect of treatment was compared to that of 20 pregnant women (group II) treated with antibiotic only. In group I recurrence of infections was found out in 15.3%, while in group II in 55%. We would like to offer it as part of the treatment of uroinfections with pregnant women, because it will reduce the usage of antibiotics and the recurrence of the uroinfections in postpartum period.

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 content of IgA, IgM, IgG and the level of specific antibodies in the blood serum of patients with bronchopulmonary diseases after a course of immunotherapy with polycomponent vaccine B[symbol: see text]-4 was studied. A rise in the concentration of IgM due to the synthesis of specific antibodies to Proteus vulgaris, Escherichia coli and Klebsiella pneumoniae was found to occur. The examination of sick children revealed that a high proportion of them (54%) showed a pronounced decrease in the level of IgA. The use of the preparation made it possible to enhance the level of IgA.

Acute otitis media (AOM) is the most frequent bacterial infection in childhood. Because of the high morbidity, the costs of AOM and growing concern about increasing resistance of pneumococci, the most common bacterial cause of AOM, prevention of AOM is important. Vaccination with the recently developed pneumococcal conjugate vaccines leads to a reduction in the number of AOM cases caused by the serotypes present in the vaccine, but the reduction in overall AOM incidence is below 10%. In particular the children with recurrent episodes of AOM may benefit more from these pneumococcal conjugate vaccines.

The results of prolonged observations on children with frequent acute respiratory diseases (ARD), subject to immunoprophylaxis with the use of polycomponent vaccine (VP-4), prepared from the antigens of opportunistic microorganisms, are presented. The vaccine was introduced to 30 children in 3 intranasal administrations and 6-8 oral administrations. The morbidity rate of the children was registered and their clinical status was evaluated for a year after the introduction of vaccine VP-4. As revealed in these observations, the frequency of ARD cases among the immunized children decreased 3 times or more in comparison with that among the same children, registered during a year prior to the introduction of the vaccine. In addition to a decrease in the frequency of ARD cases, a decrease in their duration and in the number of antibiotic administrations, as well as in the necessity of hospitalization, were also registered.

The live attenuated vaccine strains Vibrio cholerae CVD 103-HgR and Salmonella typhi Ty21a can be combined into an oral bivalent vaccine without compromising the immunogenicity of the individual vaccine strains. Seroconversion rates of 87 to 94% for Inaba vibriocidal antibodies and 72 to 91% for anti-S. typhi lipopolysaccharide antibodies (IgG or IgA) were reported in healthy European volunteers receiving a bivalent CVD 103-HgR/Ty21a vaccine-based schedule (bivalent vaccine on day 1 and monovalent Ty21a vaccine on days 3 and 5). The immunogenicity of bivalent CVD 103-HgR/Ty21a vaccine is not adversely affected by concomitant administration of mefloquine, yellow fever vaccine or oral polio vaccine. Chloroquine may reduce the immunogenicity of the CVD 103-HgR component and proguanil may reduce the immunogenicity of the Ty21a component. Bivalent CVD 103-HgR/Ty21a vaccine does not adversely affect the immunogenicity of the yellow fever YF 17D vaccine. The type, incidence and severity of adverse events seen in individuals receiving bivalent CVD 103-HgR/Ty21a vaccine-based schedules are similar to those that occur with the monovalent vaccines.

The treatment of 17 patients having chronic obstructive bronchitis with a combined vaccine resulted in a rise in the number of T lymphocytes and T suppressors, as well as a simultaneous increase in their functional activity, in these patients. Moreover, an increase in the ingestive activity of neutrophils and in the concentration of immune complexes was registered. Treatment with the vaccine containing Staphylococcus aureus, Klebsiella pneumoniae, Proteus and Escherichia coli antigens facilitated an increase in the titers of antibodies to most antigens contained in the vaccine and in the resistance of the body to infection. Vaccinal therapy made it possible to achieve a significant prolongation of the period of remission.

In two groups of 25 urological patients each, with and free of urinary infection, Urostim is administered fifteen days before and after the operation. The prophylactic effect of the drug in terms of hospital transmitted wound and urinary infections is recorded on the basis of comparative study with control groups. As shown by the results obtained, Urostim immunoprophylaxis yields positive results in urological practice. In 80 per cent of the cases development of the complication is prevented. Vaccine administration in conjunction with an updated antibiotic broadens the therapeutic scope in patients with urinary infection.