Title Neutralizacija varijanti mišjeg citomegalovirusa protutijelima
Title (english) Neutralization of mouse cytomegalovirus variants by antibodies
Author Antonela Lacković
Mentor Ilija Brizić (mentor)
Mentor Marina Pribanić Matešić (komentor)
Committee member Igor Jurak (predsjednik povjerenstva)
Committee member Katarina Kapuralin (član povjerenstva)
Granter University of Rijeka (Faculty of Biotechnology and Drug Development) Rijeka
Defense date and country 2023, Croatia
Scientific / art field, discipline and subdiscipline BIOTECHNICAL SCIENCES Biotechnology Molecular Biotechnology
Abstract Razvoj cjepiva protiv humanog citomegalovirusa (HCMV) javnozdravstveni je prioritet obzirom da virus globalno uzrokuje ozbiljne posljedice kao što su povećana smrtnost kod imunosuprimiranih pojedinaca i teške neurološke posljedice kod novorođenčadi, poput gubitka sluha i mentalne retardacije. Velik broj cjepiva za citomegalovirus je testiran u pretkliničkim i kliničkim istraživanjima, no trenutno nema odobrenog cjepiva i terapija je usmjerena na suzbijanje virusa i smanjenje simptoma infekcije. Razlog za to se djelomično nalazi u činjenici da je humoralni odgovor na infekciju citomegalovirusom nedovoljno istražen. Infekcija mišjim citomegalovirusom je najčešći korišteni model za infekciju humanim citomegalovirusom. U ovom radu korištene su ženke, 8 – 12 tjedana starosti, imunizirane s divljim tipom virusa (WT MCMV), te njihovo potomstvo, neonatalni miševi inficirani s različitim sojevima i različitim virusnim dozama. Titar sojeva virusa u organima neonatalnih miševa određen je pomoću testa virusnih čistina, a neutralizacijski kapacitet transplacentarno prenesenih protutijela određen je uz pomoć neutralizacijskog testa. Fenotipska analiza mikroglije provedena je pomoću protočne citometrije. Rezultati ovog diplomskog rada pokazuju učinkovitu neutralizaciju različitih varijanti mišjeg citomegalovirusa protutijelima prenesenim od majke inficirane divljim tipom virusa, što za posljedicu ima inhibiciju replikacije virusa u različitim organima. Daljnja istraživanja su potrebna za bolje razumijevanje uloge protutijela u sprječavanju širenja virusa, za njihovu dugoročnu učinkovitost protiv različitih varijanti te usporedbu rezultata između modela i kliničkih istraživanja.
Abstract (english) The development of a vaccine against human cytomegalovirus (HCMV) is a public health priority, as the virus globally causes serious consequences such as increased mortality in immunosuppressed individuals and severe neurological sequelae in newborns, such as hearing loss and mental retardation. A large number of vaccines for cytomegalovirus have been tested in preclinical and clinical research. However, currently, there is no approved vaccine, and therapy is aimed at suppressing the virus and reducing infec tion symptoms. The reason for this is partly due to the fact that the humoral response to cytomegalovirus infection has not been sufficiently investigated. Infection with murine cytomegalovirus (MCMV) is the most commonly used model for human cytomegalovir us infection. Females, 8 12 weeks old, immunized with the wild type virus (WT MCMV), along with their offspring, were used for this thesis, while neonatal mice were infected with different virus strains and different viral doses. The virus titer was determ ined using the plaque assay, while the neutralization capacity was determined using the neutralization assay in the presence of immune serum or serum from non immunized animals. Phenotypic analysis of the expression of MHC molecules on microglia was conduc ted using a flow cytometer. The results of this thesis show the effective neutralization of different variants of murine cytomegalovirus by antibodies transferred from a mother infected with the wild type virus, which results in the inhibition of viral rep lication in different organs. Further research is required to better understand the role of antibodies in preventing the spread of the virus, their long term effectiveness against different variants, and to correlate results obtained in mouse models and clinical studies.
Keywords
citomegalovirus
kongenitalna infekcija
neutralizacija protutijelima
test virusih čistina
Keywords (english)
cytomegalovirus
congenital infection
antibody neutralization
virus clearance test
Language croatian
URN:NBN urn:nbn:hr:193:565915
Study programme Title: Biotechnology in medicine Study programme type: university Study level: graduate Academic / professional title: magistar/magistra biotehnologije u medicini (magistar/magistra biotehnologije u medicini)
Type of resource Text
File origin Born digital
Access conditions Embargoed access Embargo expiration date: 2033-12-31
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Created on 2023-10-11 08:05:16