Utjecaj ekspresije liganda za receptor NKG2D na potencijal citomegalovirusa kao vakcinskoga vektora

doctoral thesis

• Title (english): The role of NKG2D ligand expression by cytomegalovirus on its vaccine-vector capacity
• Author: Tihana Tršan
• Mentor: Stipan Jonjić (mentor)
• Committee member: Jagoda Šušković (predsjednik povjerenstva)
• Granter: University of Zagreb; Faculty of Food Technology and Biotechnology; Zagreb
• Defense date and country: 2015-02-20, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Biotechnology
• Universal decimal classification (UDC): 578/579 - Virology. Microbiology

Abstract

Iako vakcinacija predstavlja najuspješniji pristup zaštite protiv patogena, učinkovite vakcine protiv značajnog broja patogena još uvijek nisu dostupne. Stoga su neophodni novi pristupi u dizajnu i proizvodnji vakcina. Živi atenuirani citomegalovirus (CMV) je atraktivan vakcinski vektor s obzirom na snažan odgovor posredovan CD8 T-limfocitima koji potiče u domaćinu. CMV je razvio brojne strategije izbjegavanja imunosnog odgovora domaćina, a posebice kontrole posredovane NKG2D receptorom. NKG2D djeluje kao snažan aktivacijski receptor kada je eksprimiran na NK stanicama te kao ko-stimulacijski receptor na CD8 T-limfocitima. U ovom radu pokazano je da mišji CMV (MCMV) koji eksprimira NKG2D ligand RAE-1γ služi kao izuzetno učinkovit vakcinski vektor. Koekspresija RAE-1γ i antigenskog epitopa od strane MCMV-a pojačala je odgovor posredovan CD8 T-limfocitima specifičnim za vektorski epitop i rezultirala dugotrajnom zaštitom u infekciji patogenom posredovanom upravo epitop-specifičnim CD8 T-limfocitima. MCMV vektor koji eksprimira RAE-1γ ligand bio je snažno atenuiran i jednako protektivan čak i u jedinki koje ne eksprimiraju NKG2D receptor na svojim stanicama, što ukazuje na novu, do sada nepoznatu i NKG2D neovisnu, funkciju RAE-1γ proteina.

Abstract (english)

Although vaccination proved to be successful method against various pathogens, efficient vaccine for a significant number of diseases is still not available. Therefore, new vaccine strategies are required. Live attenuated cytomegalovirus (CMV) is attractive vaccine-vector candidate due to the potent CD8 T cell response it triggers. CMV developed numerous strategies to avoid immune control of the host, especially the one mediated by the NKG2D receptor - strong activating receptor when expressed on NK cells or co-stimulatory molecule on CD8 T cells. It is demonstrated here that mouse CMV (MCMV) expressing NKG2D ligand RAE-1γ possesses the exceptional capacity to serve as a highly efficient vaccine-vector. Co-expression of RAE-1γ and foreign CD8 T cell epitope in the context of MCMV augmented epitope-specific CD8 T cell response and resulted in long-term protection against respective pathogen by means of CD8 T cells specific to the vectored epitope. RAE-1γ expressing MCMV vector was highly attenuated and equally protective even in NKG2D deficient mice, implying the existence of additional, so far unknown and NKG2D-independent, immune function of RAE1γ.

• Keywords: citomegalovirus (CMV); vakcine koje potiču CD8 T-limfocite; vakcinski vektor; NKG2D; RAE-1γ ligand
• Keywords (english): cytomegalovirus (CMV); CD8 T cell based vaccines; vaccine vector; NKG2D; RAE-1γ ligand
• Language: croatian
• URN:NBN: urn:nbn:hr:159:235346
• Promotion: 2015-07-12
• Study programme: Title: Postgraduate PhD Study in Biotechnology and Bioprocess Engineering; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti (doktor/doktorica znanosti)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2018-05-18 08:32:22