Current issue
4 . 2019
Humoral immunity

Morphine-specific antigenic and functional properties of poly- and monoclonal anti-idiotypic antibodies

Abstract

Anti-idiotypic antibodies that mimic the image of an antigen can be used as vaccines for the prevention and treatment of various diseases, including drug addiction. Their use is especially relevant in cases when the use of drugs with psychotropic effects as antigens is limited bу law. In the present work, the antigenic and functional properties of several types of anti-idiotypic monoclonal and polyclonal antibodies (Ab2) to morphine derivatives were investigated. To obtain Ab2, two types of primary monoclonal antibodies (Ab1) with different specificity were used: 3K11 and 6G1, which in turn were obtained in response to immunization with conjugates of morphine derivatives with bovine serum albumin. Immunization of the rabbits with all Ab2 obtained types stimulated the production of the third generation antibodies (Ab3), which, like the primary antibodies Ab1, interacted with the original antigens (morphine derivatives). There was a difference in the specificity of Ab1 and Ab3, detected using differential enzyme immunoassay. Monoclonal Ab1 types 3К11 and 6G1 had a narrower specificity and recognized only their immunogens, designated as conjugates KMM-BSA, FAM-BSA and GsM-BSA. In this case, Ab1 Ю1 interacted with the first two conjugates, and 6G1 - with GSM-BSA. In contrast, Ab3, obtained by immunization with the Ab2 types K11 and G1, interacted with all morphine derivatives conjugates, which were used for primary immunization. The concentration of Ab3 in response to immunization with monoclonal antibodies repeatedly exceeded the titer of antibodies obtained with the injection of polyclonal antibodies, which indicates that monoclonal Ab2 belongs to the β-type. The study of Ab2 functional activity showed that all types of these antibodies at concentrations of 37.5-75 nM, like morphine, stimulated the proliferation of T98G line glioblastoma cells, having a significant amount of opioid receptors mainly μ- and κ-types at the membrane. At the same time, morphine exerted a maximum proliferative effect at a concentration of 20 pM. The opiate receptor antagonist naloxone completely blocked the proliferative effects of Ab2 and morphine, which confirms the specificity of the obtained anti-idiotypic antibodies action.

Immunomodulators

β (1→6)-D-glucan from the fruit body of mushroom Lentinus edodes: structure and immunobiological properties

Abstract

Most, if not all, Basidiomycetes mushrooms have biologically active polysaccharides (β-glucan) showing potent immunomodulating properties. The majority of research on biological activities of glucans has focused on β-(1→3)-glucans. At the same time fungi produce a wide variety of glucans with vast differences in proportion and arrangement of their (1→3)- and (1→6)-β-glycosidic linkages. In this study, the crude water-soluble polysaccharide, which was obtained from the fruiting body of Lentinus edodes by hot water extraction and ethanol precipitation, was fractionated by Sepharose 6B column chromatographies. This process resulted purified polysaccharide fraction. The molecular mass of isolated fraction was estimated by gel filtration to be 500–2000 kDa. 1H- and 13C-NMR spectra indicate that purified polysaccharide is a branched β-glucan with a main chain that consists of β-D-(1→6) linked Glcρ residues substituted at O-3 by single-units of β-Glcρ. Isolated β-(1→6)-glucan increased in vitro production of TNF-α, INF-γ and IL-1β but did not stimulated IL-2, IL-4 and IL-5 production by spleen cells of mouse. Furthermore, β-(1→6)-glucan enhanced in vitro maturation of dendritic cells. It increased CD83, CD86 and MHC II antigen expression in the final stages of differentiation of these cells. Our findings suggest that not only β-(1→3)-glucan, but also other β-glucans inclusive β-(1→6)-glucans should be considered in future research, in particular, as immunomodulatory agents.

Vaccines and vaccination

Influence of the recombinant vaccine against pseudomonas infection on humoral immune response and protective activity in mice

Abstract

Pseudomonas infection is a serious socio-economic problem of public health, as the pathogen has a high level of resistance to antibiotics, and the clinical manifestations of the disease are characterized by diversity and, often, severe course. The aim – study of antibody response in mice vaccinated with candidate vaccine against Pseudomonas aeruginosa, characterization of the spectrum of subisotypes of the produced immunoglobulins.

Material and methods. Mice were injected intraperitoneally at 2-week intervals with a recombinant vaccine against P. aeruginosa (25 µg of OprF and 50 µg of a-Tox (toxoid), sorbed on 225 µg of aluminum hydroxide gel). 3 weeks after the last immunization of mice, antibody levels were determined by ELISA and the protective activity of the vaccine upon infection with a lethal dose of P. aeruginosa.

Results. Twice immunization of mice with a recombinant vaccine against P. aeruginosa induced an increase (p < 0.01) in mice blood of IgM and IgG titers, as well as IgG1, IgG2a, IgG2b and IgG3 isotypes to OprF and a-Tox compared to control (non-vaccinated mice). At the same time, the vaccine protected mice from a lethal infecting dose of P. aeruginosa in 80% of cases.

Conclusion. It can be assumed that the action of the vaccine based on recombinant OprF protein and P. aeruginosa toxoid is associated not only with the induction of antibodies, but also with the activation of the cellular mechanisms of the immune response.

Methods

The problems connected with unwanted immunogenicity of biotechnological medicines (therapeutic proteins). Part 2. Clinical aspects

Abstract

Biotechnological medicines, the so-called therapeutic proteins in some patients can cause the development of an immune response, which may not be clinically manifested or provoke immune-mediated adverse reactions. Manifestations of the unwanted immunogenicity of therapeutic proteins depends on the properties of the medicine, characteristics of the patient and the underlying disease, as well as on the dosage, dosing schedule, the route of administration of the drug, concomitant therapy, etc. The review provides information on the clinical manifestations of the immune response to therapeutic protein, its consequences on pharmacokinetics, safety and efficacy of the medicine. The information on the principles of immunogenicity study and risk assessment of unwanted immune response at the stage of development, preclinical and clinical studies and after medicine marketing authorization is given.

Reviews

Key role of tumor-associated macrophages in the progression and metastasis of tumors

Abstract

Tumor-associated macrophages (TAM), the predominant leukocyte subclass in solid tumors, show high degree of phenotypic and functional heterogeneity under the influence of the local tumor microenvironment. TAM with antiinflammatory and protumorogenic activity modulate the microenvironment, promote tumor growth, invasion of tissue surrounding the tumor and metastasis to distant sites. They promote angiogenesis, tumor resistance to chemotherapy and radiotherapy and provide a supportive environment for the tumor to avoid immune surveillance. In tumor sites, TAM usually are alternatively activated or M2 macrophages secreting anti-inflammatory cytokines, interleukin (IL) -10, prostaglandin E2 and expressing CD206- and CD163-receptors, as well as CCL2-, CCL17- and CCL22-chemokines involved in attracting regulatory T-cells (Treg). Data from clinical and experimental studies suggest a high TAM density in the tumor with an unfavorable prognosis for patients. The use of TAM as therapeutic targets in many types of tumors is an important strategy based on the selection of agents that either inhibit the attraction of TAM in the primary tumors and metastatic sites or convert protumor TAM to antitumor effector cells.

Prospectives of application of the genetically modified lymphocytes with chimeric T-cell receptor (CAR-T-cells) for the therapy of solid tumors

Abstract

In recent years new methods of adoptive cell therapy using genetically engineered T-cells have been introduced into clinical practice of oncology. Modification of chimeric antigenic receptors (CARs) confers T-cells with specific antitumor cytotoxicity and, thus, induces immune response against malignant neoplasms. Despite the significant success of these strategies in hemoblastoses, targeting CAR-T-cells to solid tumors is more difficult due to the characteristics of the histopathological structure, lack of specific antigens and the immunosuppressive environment of solid tumors. In addition, toxicity caused by the relative target expression in normal tissues is another problem that should be considered. This review is devoted to analysis of factors limiting the use of CAR-T-cell therapy in the treatment of solid tumors and description of some new approaches that are considered promising for overcoming these obstacles.

The role of residual xenoanthigens in the degeneration of xenogenic bioprosthetic heart valves

Abstract

Xenogenic tissue heart valves are superior to mechanical heart valves prostheses in terms of optimal hydrodynamics and low thrombogenicity which does not require lifelong anticoagulant therapy. However, xenotissue heart valves are apt to calcification limiting their widespread use, especially in children and young adults. Recently, there are a lot of data suggesting that humoral and cellular immune response have been involved in the degeneration of xenotissue heart valves in addition to passive physical and physicochemical processes. The main triggers of the immune response to xenotissue implants are carbohydrate antigens, such as galactose-α-1,3-galactose and N-glycolylneuramic acid. We assume that the improvement of biomaterial chemical modification and/or use of knockout animals for the valve device manufacture may increase the life of xenotissue heart valves and reduce the number of reoperations.

Vaccines for the treatment of malignant neoplasms

Abstract

Malignant cells capable to form tumors arise as a result of mutations in the genes of somatic cells. Mutant proteins, mutated gene products and impaired expression of non-mutated genes make malignant cells distinct from other cells in the body. Immune system is able to recognize these differences. Appropriate immune response against altered antigens allows the organism to prevent the development of malignant neoplasms. When a tumor in an individual has arisen and develops, it remains possible to induce immune response against malignant cells and thus stop or slow down the progression of cancer, in some cases it is even possible to achieve a complete recovery of the patient.

Therapeutic antitumor vaccination is a method of immunotherapy of cancer patients, that targets an induction of adaptive immune responses specific to tumor antigens. Recent advances in the field of immunology and genetics of tumors allow for a comprehensive analysis of the multitude of tumor antigens of a particular patient, to select the best immunogenic epitopes for this patient, which contributes to significant progress in the development of therapeutic antitumor vaccines. This review considers the main approaches in the development of therapeutic antitumor vaccines, which are currently at different stages and demonstrate significantly different clinical efficacy.

Chronicle

100 years of the L.A. Tarasevich State Research Institute of Standardization and Control of Medical Biological Preparations. Its role in improvment of the system of state quality control of immunobiological preparations in Russia

Abstract

Strategies of precision medicine in modern clinical immunology and allergology

Abstract

Resolution of United immunological forum – 2019

Abstract
Anniversary

Tatiana Mikhailovna ANDRONOVA

Abstract

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)


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