Unit:
Τομέας Φυσιολογίας Ζώων και ΑνθρώπουLibrary of the School of Science
Author:
Μαργαρώνη Μαρίτσα
Dissertation committee:
Αικατερίνη Γαϊτανάκη Καθηγήτρια (Επιβλέπουσα), Ουρανία Τσιτσιλώνη, Αναπληρώτρια Καθηγήτρια Ευδοκία Καραγκούνη Διευθύντρια Ερευνών
Original Title:
Ανάπτυξη πειραματικού εμβολίου εναντίον ενδοκυτταρικών παθογόνων
Translated title:
Development of experimental vaccine against intracellular pathogens
Summary:
The aim of the present study was to investigate the ability of
poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) to induce protection
against experimental visceral leishmaniasis. Nanoformulations based on PLGA NPs
were synthesized and encapsulated a crude mix of proteins from Leishmania
infantum promastigotes (sLiAg) and MPLA, as adjuvant. PLGA NPs were
surface-modified with a synthetic 8-peptide mimicking the TNFα docking region,
in order to enhance dendritic cell targeting.
Surface modified PLGA NPs were taken up more efficiently from dendritic cells
compared to non-modified NPs. This is attributed to possible enhancement of
dendritic cell targeting, as well as to the reduction of the absolute value of
z potential. Incorporation of sLiAg and/or MPLA and surface modification with
p8 induced the maturation and functional differentiation of dendritic cells
resulting in their enhanced ability of presenting parasitic antigens and
activating in vitro T cells. Vaccination of BALB/c mice with PLGA-sLiAg-MPLA or
p8-PLGA-sLiAg NPs induced long-lasting protection against L. infantum infection
due to activation of T helper and cytotoxic T cell populations and simultaneous
suppression of TH2 and regulatory T cell subpopulations. Based on the above
results, the nanoformulations used are suggested as candidate vaccines against
visceral leishmaniasis.
Keywords:
Intracellular pathogens, Leishmaniasis, Vaccines, Nanoparticles, PLGA
Number of references:
433
