Vaccines are the most effective and cost-efficient means for preventing diseases caused by infections pathogens. Despite the great success of vaccines, development of safe and strong vaccines is still required for emerging new pathogens, re-emerging old pathogens, and in order to improve the inadequate protection conferred by existing vaccines. Therefore, the development of more efficient and safe adjuvants and vaccine delivery systems to obtain high and long-lasting immune responses is of primare importance. The new generation vaccines consisting of particulate systems have been suggested and developed to be used as potent adjuvant to overcome and extirpate of dangerous and/or fatal diseases. The particulate systems made from biopolymers have promising properties and safety to be used as carriers and adjuvant for vaccine delivery. These systems can offer three different mechanisms: targeting of antigens to the relevant antigen-presenting cells of the immune system, i.e. macrophages; direct activation of cells in the immune system; and providing controlled-release properties for encapsulated protein and leading to the increase of the immune response in the body. Recent reports have revealed the importance and advantages of nanoparticles(NPs) over microparticles. While compared with the microparticles, the advantages of NPs are their ability to improve biological agent encapsulation, pharmacokinetics, bioavailability as well as biological activity.. The use of nanoparticles in vaccine formulations allows not only improved antigen stability and immunogenicity, but also targeted delivery and slow release. A number of nanoparticle vaccines differencing in composition, size, shape, and surface properties have been approved. However challenges remain due to a lack of the fundamental understanding of the mechanisms of nanoparticles action.
For the development of effective vaccines. the biodegradable polymeric substances show great promise. Number of the nature polysaccharides as chitosan, inulin, alginate and other has been used to prepare micro or nanoparticles as new vaccine delivery system. Among these polysaccharides pectins attract a significant interest due to its unique properties.
Pectin are a biodegradable, and mucoadhesive polymers that does not produce toxicity. Also, pectin particles have not been observed to agglomerate in any of the major organs. Pectine posses wide spectrum of physiological activity, including immunomodulation action. A high ability as antimicrobial, anticancer, and chemosensitizing agents was observed for complexes of pectin with biocompartible metals. It was established that some metalocomplexes of pectin were capable of enhancing the antitumor effect of certain cytostatic agents while decreasing their toxic effect. The chemical composition, molecular structure, and physico-chemical properties of pectin allow to get a different modifying forms of pectin and vaccines adjuvants on the base of these forms of pectin: emulsions, gels, self- assembly systems.
The goal of present Project is preparation of modifying pectins nanoparticles, usage of these nanoparticles as vaccine delivery systems and evaluation of immune responses.
In order to achievement of this goal it is necessary to solve the following tasks:1. To isolate of pectin from sugar beet Beta vulgaris, to determinate of the chemical composition and characteristic properties of these products.
2. To obtain of the modified forms of pectin (low methylated (LM) fraction, pectic acid, hydrophobically enriched pectin) and characterization of their structure and chemical composition
3. To prepare biodegradable pectin nanoparticles (NPS) by use of different methods: ionic gelation, emulsion evaporation techniques; self-assembling.
4. To estimation of the composition, structure and physico-chemical parameters of obtained NPS.
5. To formulation of the vaccine by including of bioagent (strain plogue microbes Yershinia Pestis ) within NPS obtaining by use of different methods.
6. To characterize of the formulated vaccine composition with respect to size, zeta potencial, morphology, encapsulation efficiency and other properties.
7. To assess of the quality of specific immune response after vaccination.
8. To estimate of intencity of immune response.
Theoretical basis of the development of this proposal is large-scale studies of the project participants, in particular, of research on structure, reaction ability, and biological activities of pectin substances (Ashubaeva et al. 1991; Aimuchamedova et al. 2003, 2004; Khudaibergenova et al. 2006). More important in our recent researches are synthesis of the nanosized pectin-based formulations and usage of these materials for adjuvant chemotherapeutics (Kydralieva et al. 2012; Jorobekova et al. 2012; Kudaibergenova et al. 2015). Some works in the field of immunology were established.. Most significant among these researches are the studies of the macrophage-lymphocyte interactions, and also of immunomodulation of the vaccines (Adambekov et al. 1998, 2015).
Accomplishment of the Project will allow increasing of the investigations in the field of nanovaccinology. The innovation technique will be developed and carried to the industry:
