Experimental liposomal viral vaccine safety

Abstract

Introduction. With the transport links development there is rather important issue respiratory viral infections spread, especially influenza. The only method controlling influenza is vaccination. Search and development effective and safe vaccines is important.  Material and methods.  In base SO "Mechnikov Institute Microbiology and Immunology National Ukrainian Academy Medical Sciences" in the scientific theme "Developing new approaches to creating viral vaccines and study specific activity depending of type and degree component`s modification" was created several experimental influenza vaccine with subsequent component`s modification for selecting the most optimal pattern of safety and immunogenicity. In assessing the influenza vaccine safety is using a few criteria, including, reactivity, as measured by the frequency of local and systemic adverse (negative) effects, which due to its introduction, and for lipid content drugs, ability to influence oxidation processes. At present study phase was determined: a) systemic reaction and local reaction of delayed-type hypersensitivity (foot pad swelling assay); b) lipids and proteins peroxidation processes after administration officinal and experimental vaccines (content protein’s carbonyl groups, lipid’s hydroperoxides, activity of glutathione-peroxidase). Study objects were trivalent seasonal influenza vaccine, "Vaxigrip" (Sanofi Pasteur, S.A., France), "Inflexal V" (Biotech Ltd. Berne, Switzerland) and experimental vaccine samples. Highest immunogenicity vaccines had undergone improvements and modifications using adjuvant systems and acylation influenza proteins.  Liposomes 2 – the experimental influenza vaccine with a liposome negative charge and antigenic composition like split vaccines "Vaksihryp". Liposomes 2.1 - the adjuvant experimental influenza vaccine with modifications liposomal components (etoniy and chlorophyllipt molecules embedded in liposomal membrane). Liposomes 2.2 - the adjuvant experimental influenza vaccine further modification through acylation antigenic component. Results and discussion. Among the vaccines with the antigenic component modification and addition of adjuvants, the highest production of specific influenza antibodies was observed after administration liposomes №2.2 sample, which was made on the basis of antigen Vaxigrip with negatively charged liposomal formulation, the addition of adjuvants and modification antigenic composition, the second ranked liposomes №2.1, without antigenic modification. The study identified regarding the frequency of local reactions, assessed by visual observations, among experimental animals in injection site after legalized vaccines or newly samples weren`t characterized by the formation of swelling, hardening of tissue hyperemia or painful local reactions throughout the observation time. Experimental mice also haven`t fever for the 5 days after manipulation, which is the main criterion of systemic adverse reactions after they administered vaccine preparations. Also after use of experimental drugs and drug comparison, subjective, wasn`t happened abnormalities in general condition animals, including a decrease in appetite, digestive disorders, changes in activity and more. These observations, however, do not allow to conclude the complete safety newly created experimental vaccine and require additional evaluation tests. As base component for building experimental liposomal vaccine used the fosfatydilholin (FH).  FH is a substrate for activation lipid peroxidation. Lecithin liposomes, that are liposomal vaccine structural and functional components, are exposed to a variety number of physical and chemical factors. One of biochemical events, that happen to them, are lipid peroxidation, accompanied by free radicals appearance in the system and, ultimately, causes phospholipid bi-layer membranes degradation by a violation of their permeability and lysis. In this regard, system safety control and liposomal drug efficacy should include the definition the content lipid peroxidation products. Conclusion. Thus, experimental samples influenza liposomal vaccine (without modification and with its for liposomal and antigenic components) haven`t found increased levels primary products lipid peroxidation – lipid hydro peroxides and protein oxidation products – carbonyl protein and haven`t significant effects inhibition anti-oxidant enzymes in rat`s serum. More results the study stage the safety most effective vaccine samples will be present in the text.