INFLUENCE OF POLYOXIDONIUM, Poly(I:C), DALARGIN ON THE PROTECTIVE EFFICACY OF YERSINIA PESTIS VACCINE STRAIN EV LINE NIIEG IN EXPERIMENTAL PLAGUE

Background. The live-attenuated vaccine based on the Yersinia pestis strain EV line NIIEG is still used in Russia, providing protective efficacy against plague. Nevertheless, there is an urgent need for developing new ways to increase the immunogenicity of the Y. pestis EV NIIEG vaccine strain. In this study, the ability of direct action of immunoadjuvant azoximer bromide (polyoxidonium, PO) on the immunobiological properties of vaccine strain Y. pestis EV NIIEG during cultivation on a dense nutrient medium was evaluated. Materials & Methods. Y.pestis EV NIIEG, cultivated at 28 °С for 48 h on LB agar, Miller pH 7.2 ± 0.1 (Sigma-Aldrich, USA) with the addition of PO and without. MALDI-TOF mass-spectrometry was deployed for the obtainment of mass-spectra of ribosomal proteins from Y. pestis EV NIIEG cells on the MicroflexTM LT mass spectrometer (Bruker Daltonics, Germany). Protective efficacy was evaluated under subcutaneously challenge guinea pigs and mice BALB's with 400 LD50 doses of the Y. pestis 231, Y. pestis P-13268 Vietnam (MLD=5 CFU). Antibody titers to F1 in serum were determined using an ELISA. Results. The addition of the therapeutic concentration of PO in the cultivation medium induced a significant increase in the immunogenicity of Y. pestis EV NIIEG that resulted in enhancement of serum antibody levels against Y. pestis F1 antigen and several times the growth of protective efficacy in the bubonic plague model on two types of experimental animals. ImD50 of the vaccine strain Y. pestis EV NIIEG, cultivated with PO, was significantly (p < 0,05) lower in comparison to ImD50 for Y. pestis EV NIIEG in standard cultivation conditions. One year of storage at a temperature of 4 °С did not alter the protective properties of the vaccine strain Y. pestis EV NIIEG, cultivated with PO. Conclusions. Morphological studies confirmed the absence of influence PO introduction into the cultivation environment on the safety of the vaccine strain. MALDI-TOF MS profile of the Y. pestis EV NIIEG, cultivated with PO, had peaks characteristic features. The mass peak at m/z 3,061 was significantly down-regulated and new mass peaks at m/z 2,759, m/z 3,533 were determined. These changes are accompanied by the increase of Y. pestis EV NIIEG immunogenicity.

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Enhancement of the Yersinia pestis EV NIIEG Vaccine Srain Immunogenic and Protective Activity under Cultivation with Azoxymer Bromide (Polyoxidonium)

Щуковская

Goncharova

Бугоркова

et al. 2022

Epidemiology and Vaccinal Prevention

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The influence of immunomodulators on the formation of vaccine-induced cholera immunity

Филиппенко¹,

Иванова²,

Омельченко³

et al. 2022

Journal of microbiology, epidemiology and immunobiology

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Introduction. Due to the remaining tense situation on cholera in the world, research continues on the creation of new preventive drugs, as well as ways to increase the immunogenicity of existing anti-cholera vaccines. The combined use of vaccines with immunomodulators and cytokines is successfully used for the specific prevention of various infections, including particularly dangerous ones.The aim of the work is an experimental study of the effect of immunomodulators on the immunogenic and protective activity of the cholera bivalent chemical vaccine in order to assess the possibility of their use to improve the specific prevention of cholera.Materials and methods. The parameters of cellular and humoral local and systemic immune response in experimental animals vaccinated and receiving immunotherapy, as well as the effect of immunomodulators on the protective activity of antigens that are part of the cholera bivalent chemical vaccine, were evaluated.Results. The studies revealed that the use of immunomodulators in combination with the vaccine leads to an increase in the immunogenic properties of antigens. Immunomodulators stimulate the differentiation of CD4⁺- lymphocytes, ensuring the development of an immune response mainly along the humoral pathway, increase the number of B-lymphocytes, antigen-specific antibody-forming cells, as well as secretory immunoglobulin A in the intestines of vaccinated experimental animals. It is shown that the immunomodulator glucosaminylmuramyl dipeptide increases the protective properties of the antigens that are part of the chemical cholera bivalent vaccine. It was the most effective additive, since it protected all the animals included in the experiment from generalized cholera.Conclusion. The use of immunomodulators in anti-cholera vaccination, especially with glucosaminylmuramyl dipeptide, may be one of the approaches to improving the specific prevention of cholera.

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Increasing the immunogenic and protective activity of the vaccine strain Yersinia pestis EV line NIIEG using synthetic immunomodulators

Goncharova¹,

Бугоркова²,

Щуковская³

2023

Journal of microbiology, epidemiology and immunobiology

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Introduction. One of the main tasks of specific plague prevention remains the development of vaccines and their application schemes aimed at improving the effectiveness of vaccination through the use of adjuvants and immunomodulators. The purpose of the study were comparative evaluation of the effect of drugs from the group of synthetic immunomodulators on the immunogenic and protective properties of the Yersinia pestis EV line NIIEG vaccine strain in model animal experiments. Materials and methods. White mice and guinea pigs were immunized with the vaccine strain Y. pestis EV line NIIEG. The animals of the experimental groups were injected with oligopeptides O1 (Threonyl-glutamyl-lysyl-lysyl-arginyl-arginyl-glutamyl-threonyl-valyl-glutamyl-arginyl-glutamyl-lysyl-glutamate), O2 (Glutamyl-cysteinyl-glycine disodium) and O3 (Arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine) one hour before vaccination or three times before infection. On days 3, 14 and 21, antibody and cytokine products were studied. Animals were infected with the test strain Y. pestis 231(708) at a dose of 400 LD50. Results. It was found that a single administration of immunomodulators 1 hour before vaccination did not change the susceptibility of animals to the plague microbe: ImD50 = 5860 (O1); 5860 (O2); 6454 (O3) and 6876 (control) CFU for white mice and 446 (O1), 551 (O2), 446 (O3) and 578 (control) CFU for guinea pigs. Three-time administration of drugs to vaccinated animals led to a decrease in the ImD50 Y. pestis EV line NIIEG indicators in the group with O1 by 2.2 times (mice) and 1.8 times (guinea pigs), with O2 and O3 by 1.2 times, regardless of the biomodel compared with the control. The stimulating effect of O1 and O3 on the production of antibodies to F1 of the plague microbe and cytokines interferon-gamma, interleukin-10 has been established. Conclusion. The stimulating potential of synthetic immunomodulators on the immune system of biomodels immunized by Y. pestis EV line NIIEG has been demonstrated, which determines the prospects of research to improve the schemes of prophylactic vaccination against plague.

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INFLUENCE OF POLYOXIDONIUM, Poly(I:C), DALARGIN ON THE PROTECTIVE EFFICACY OF YERSINIA PESTIS VACCINE STRAIN EV LINE NIIEG IN EXPERIMENTAL PLAGUE

Cited by 5 publications

References 20 publications

Enhancement of the Yersinia pestis EV NIIEG Vaccine Srain Immunogenic and Protective Activity under Cultivation with Azoxymer Bromide (Polyoxidonium)

Enhancement of the Yersinia pestis EV NIIEG Vaccine Srain Immunogenic and Protective Activity under Cultivation with Azoxymer Bromide (Polyoxidonium)

The influence of immunomodulators on the formation of vaccine-induced cholera immunity

Increasing the immunogenic and protective activity of the vaccine strain Yersinia pestis EV line NIIEG using synthetic immunomodulators

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