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Preparation and characterization of surface-modified nanoliposomes using click chemistry techniques
Frydrychová, Aneta ; Bartoš,, Milan (referee) ; Turánek, Jaroslav (advisor)
Over the past decades the liposomes have been intensively studied for their unique properties which predispose them for use as drug delivery systems or for constructions of vaccines. This diploma thesis provides an overview of their most important properties, preparation options and their surface modification. The aim of this thesis is thus a preparation and characterization of the nanoliposomes and their surface modification. The liposomes were prepared by lipid film hydration method and mannan polysacharide was used for surface modification. Due to the use of a lipid with an N-oxy group, the modification was carried out via an oxime ligation via click chemistry. Nanoliposomes were characterized by series of physicochemical methods such as TEM, DLS, FT-IR or nano-flow cytometry. Part of the thesis is a study of the interactions of liposomes accomplished on selected cell lines to verify whether they stimulate immune response pathways. Its results confirmed activation of the NLRP3 inflammasome leading to the production of pro-inflammatory cytokines (IL-1). Thus, these polymer coated nanoliposomes are potentially useful as vaccine adjuvants.
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Human papillomavirus - prevention of cervical cancer and awareness of high school students about HPV viruses and their prevention
Dinga, Jana ; Thorovská, Alena (advisor) ; Zvírotský, Michal (referee)
This bachelor thesis is mainly focused on human papillomaviruses (HPV viruses), cervical cancer and primary prevention against HPV viruses. In the theoretical part, basic information about these viruses is described - from their history, epidemiology, risk factors that support the spread of viruses, to the ways of transmission of HPV infection and the division of HPV viruses according to their level of danger. The work also describes selected diseases caused by HPV viruses. Specifically, the work describes "less serious" genital warts (their epidemiology and incidence, mode of transmission and the way to treat or prevent this disease). A significant part of the work is devoted to cervical cancer as a disease caused by high-risk types of HPV viruses. The course of the disease and its individual phases are described in the thesis - from precancerous stages of cervical cancer to cervical cancer itself. A significant part of the work is devoted to the epidemiology of this disease and especially the possibilities of prevention against it (primary prevention, secondary prevention, etc.). In the research part, using the quantitative research method, I devised a questionnaire that was intended for high school students from the first to the fourth grade. Using the analysis of the results of the...
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Analysis of the influence of international economic relations on the supply of the vaccines against COVID-19 to African countries
Mejstřík, Václav ; Kofroň, Jan (advisor) ; Guasti, Petra (referee)
This bachelor's thesis examines the factors influencing the distribution of COVID-19 vaccines to African countries. The research builds on current literature on the economic and other penetration of states into Africa. Specifically, the thesis examines the penetration of China, Russia, the United States of America, and European Union member states along with the United Kingdom. The broader aim of the thesis is to provide insight into the motivations of vaccine-providing states. In other words, whether vaccines are being used as a geopolitical tool to gain influence. This is an exploratory-quantitative study using statistical analysis, specifically OLS regressions. The research was carried out using a multivariate regression method, with each model created by repeating a simple regression. In total were created five models with five independent variables. The independent variables are GDP per capita, imports, exports, democracy index score and presence of diplomatic missions. The operationalization produced five dependent variables representing a total of seven types of vaccines. Only the variables for the democratic index score and GDP per capita showed a significant effect on vaccine supply, but they can only explain the variability in vaccine supply for Oxford-AstraZeneca, Moderna, Johnson &...
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Preparation and characterization of surface-modified nanoliposomes using click chemistry techniques
Frydrychová, Aneta ; Bartoš,, Milan (referee) ; Turánek, Jaroslav (advisor)
Over the past decades the liposomes have been intensively studied for their unique properties which predispose them for use as drug delivery systems or for constructions of vaccines. This diploma thesis provides an overview of their most important properties, preparation options and their surface modification. The aim of this thesis is thus a preparation and characterization of the nanoliposomes and their surface modification. The liposomes were prepared by lipid film hydration method and mannan polysacharide was used for surface modification. Due to the use of a lipid with an N-oxy group, the modification was carried out via an oxime ligation via click chemistry. Nanoliposomes were characterized by series of physicochemical methods such as TEM, DLS, FT-IR or nano-flow cytometry. Part of the thesis is a study of the interactions of liposomes accomplished on selected cell lines to verify whether they stimulate immune response pathways. Its results confirmed activation of the NLRP3 inflammasome leading to the production of pro-inflammatory cytokines (IL-1). Thus, these polymer coated nanoliposomes are potentially useful as vaccine adjuvants.
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Inovation in influenza vaccines
Satoriová, Martina ; Drda Morávková, Alena (advisor) ; Motlová, Lucia (referee)
Influenza viruses annually infect 3 to 5 millions of people worldwide, cause annually many hospitalizations, 250 000-500 000 deaths and significant economical losses. The vaccines still remain the most efficient way of prevention of this infectious disease. Conventional egg- based vaccines are used for more than 60 years. Although they are safe, they have many disadvantages. Their main disadvantage is the relatively low effectiveness and time-limited induced immunity. The need for annually updates of their composition due to an antigenic variability of viral surface proteins can be considered a disadvantage as well. What is more, the dependence on an egg suply and a way too long time of preparation might be limiting in the case of pandemic. The development of an universal vaccine that would induce a broad imunne response against different strains of Influenza and longlasting protection is a worldwide priority.
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In vitro evaluation of novel Toll-like receptor ligands II.
Machalová, Vanda ; Trejtnar, František (advisor) ; Janočková, Jana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Vanda Machalová Supervisor: doc. PharmDr. František Trejtnar, CSc. Title of diploma thesis: In vitro evaluation of novel Toll-like receptor ligands II. The aim of this diploma thesis was to test the new substances at Toll-like receptors (TLR), namely TLR4 and TLR8 subtypes, as potential vaccine adjuvants. Adjuvants are required for new subunit vaccines to promote stimulation of a sufficient immune response. Stimulation of TLR receptors is safe and leads to the activation of both innate and adaptive immunity and to subsequent specific immune response. Testing was carried out on cell lines stable co-expressing the respective receptors, with colorimetric activity detection. In this work, both agonist and antagonist activity at TLR4 and TLR8 receptors was investigated and a half maximal effective concentration (EC50) of resiquimod was determined. Based on the results, the respective substances cannot be considered as potential adjuvants to the TLR8 receptor and DM014 exhibits the potential for agonist activity on the TLR4 receptor, whereas the substance DM015 can be used on further investigation of immunosuppression in autoimmune diseases and diseases associated with excessive activation of the...
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In vitro evaluation of novel Toll-like receptor ligands I.
Hudáková, Kristína ; Trejtnar, František (advisor) ; Soukup, Ondřej (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Kristína Hudáková Supervisor: doc. PharmDr. František Trejtnar, CSc. Title of diploma thesis: In vitro evaluation of novel Toll-like receptor ligands I Vaccination against preventable infections prevents millions of deaths each year. Their immunity enhancing activity is strengthened by the presence of vaccine adjuvants. Development of vaccine adjuvants leads to improved safety profile and also can play a vital role in the research of new vaccines against pathogens against which the vaccines currently do not exist. The main aim of this diploma thesis was to verify the ability of rationally developed small molecule ligands to influence Toll-like receptors and thus their potential to be utilized as vaccine adjuvants. The assay was carried out using modified cell lines continually expressing the human TLR4 or TLR8 whose activation leads to production of secreted embryonic alkaline phosphatase. Ten analyzed substances labelled as DM 001 - DM 010 were examined for their agonistic and also antagonistic properties while interacting with the TLRs. Immunomodulatory activity of these tested samples was then determined by quantification of secreted alkaline phosphatase with the help of a colorimetric...
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Experimental and clinically used vaccines based on vaccinia virus
Pilná, Hana ; Mělková, Zora (advisor) ; Šroller, Vojtěch (referee)
Vaccinia virus (VACV) is an enveloped DNA virus belonging in the Orthopoxviridae genus. It is a laboratory virus in which the natural host and exact origin remain unclear. However it is of great significance for human kind. First of all, different VACV strains were used for preparation of vaccines used in the smallpox eradication campaign. Even today a significant effort is made to prepare more efficient and safer vaccines against smallpox, namely because of still remaining concerns that variola virus - causative agent of smallpox - could be misused as a biological weapon. Advances in genetic engineering allowed use of VACV for additional purposes, namely as a vaccination and expression vector. VACV enables insertion of large pieces of foreign DNA into its genome and expression of this DNA in a host. Furthermore VACV replicates exclusively in a cytoplasm, decreasing a risk of incorporation of the viral DNA into the host genome. These and other features make VACV an ideal candidate as a vector for preparation of recombinant vaccines against various infectious and oncological diseases. This thesis provides a summary of both clinically used and experimental vaccines derived from VACV. Powered by TCPDF (www.tcpdf.org)
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In vitro evaluation of novel Toll-like receptor ligands I.
Hudáková, Kristína ; Trejtnar, František (advisor) ; Soukup, Ondřej (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Kristína Hudáková Supervisor: doc. PharmDr. František Trejtnar, CSc. Title of diploma thesis: In vitro evaluation of novel Toll-like receptor ligands I Vaccination against preventable infections prevents millions of deaths each year. Their immunity enhancing activity is strengthened by the presence of vaccine adjuvants. Development of vaccine adjuvants leads to improved safety profile and also can play a vital role in the research of new vaccines against pathogens against which the vaccines currently do not exist. The main aim of this diploma thesis was to verify the ability of rationally developed small molecule ligands to influence Toll-like receptors and thus their potential to be utilized as vaccine adjuvants. The assay was carried out using modified cell lines continually expressing the human TLR4 or TLR8 whose activation leads to production of secreted embryonic alkaline phosphatase. Ten analyzed substances labelled as DM 001 - DM 010 were examined for their agonistic and also antagonistic properties while interacting with the TLRs. Immunomodulatory activity of these tested samples was then determined by quantification of secreted alkaline phosphatase with the help of a colorimetric...
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In vitro evaluation of novel Toll-like receptor ligands III
Tamášiová, Linda ; Trejtnar, František (advisor) ; Pejchal, Jaroslav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Linda Tamášiová Supervisor: doc. PharmDr. František Trejtnar, CSc. Title of diploma thesis: In vitro evaluation of novel Toll-like receptor ligands III Research on new ligands with potential immunomodulatory activity is a tool for the development of new immunological adjuvants for use in vaccines, or as separate immunomodulators in the treatment of various diseases. The aim of this thesis was to analyze the ability of new ligands to stimulate toll-like receptors 4 (TLR4) and to assess the potential for further use of these substances based on established immunomodulatory activity. The analysis was performed on modified TLR4-expressing cell lines whose activation was subsequently detected using a colorimetric-enzymatic reaction. Sixteen new substances were tested for TLR4 receptor activation in comparison with a standard agonist. The results showed a significant TLR4 agonistic activity in several of the test substances, suggesting that they are activating ligands of the receptor tested. However, due to their low solubility, some of these substances are not suitable candidates for further use and testing. Taking all parameters into consideration, among of all of the evaluated substances that...
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