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Uri Galili PhD, UMass Medical School (retired) A NOVEL APPROACH FOR INHIBITING PROGRESSION OF FLU VIRUS INFECTION AT EARLY STAGES OF THE DISEASE BY INHALATION.

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Presentation on theme: "Uri Galili PhD, UMass Medical School (retired) A NOVEL APPROACH FOR INHIBITING PROGRESSION OF FLU VIRUS INFECTION AT EARLY STAGES OF THE DISEASE BY INHALATION."— Presentation transcript:

1 Uri Galili PhD, UMass Medical School (retired) A NOVEL APPROACH FOR INHIBITING PROGRESSION OF FLU VIRUS INFECTION AT EARLY STAGES OF THE DISEASE BY INHALATION OF  -GAL/SA LIPOSOMES

2 aa Cell membrane -gal epitope sialic acid-SA epitope  Ligand of HA on flu virus is sialic acid (SA) Ligand of anti-Gal antibody is  -gal epitope phospho- lipid SA glyco- lipid  -gal glyco- lipid HA NA Gal

3  -gal epitope synthesis Anti-Gal antibody production SA, Fuc Galili Sci & Med Sept./Oct. 1998, pp. 32-41.

4 ANTI-GAL MEDIATED CHEMOTAXIS OF MACROPHAGES BY COMPLEMENT ACTIVATION AND PHAGOCYTOSIS BY Fc/Fc RECEPTOR INTERACTION C5a, C3a Fc

5  -gal/SA liposome

6 Interaction of flu virus and of anti-Gal antibody with  -gal/SA liposomes MHC peptide

7  -Gal  -gal liposome 10(15)  -gal/mg  -GAL LIPOSOMES: LIPOSOMES PRESENTING MULTIPLE  -GAL EPITOPES

8 10  m Recruitment of macrophages by  -gal liposomes (10mg) into PVA sponge discs implanted subcutaneously in GT-KO mice  -gal nanoparticles saline Galili et al. BURNS 36: 239-251, 2010

9 Recruitment of macrophages within 24h by  -gal liposomes(10mg) injected intradermal in  1,3GT knockout mouse (GT-KO mice) Hematoxylin & eosinAnti-macrophage Ab (F4/80)

10 BINDING OF  -GAL LIPOSOMES TO MACROPHAGES VIA Fc/FcR INTERACTION WITH ANTI-GAL ON THE LIPOSOMES Galili U. TOTERMJ 6: 1-11, 2013.

11 MACROPHAGE CD8+ T cell SIINFEKL T cell receptor UPTAKE OF  -GAL LIPOSOMES CONTAINING OVALBUMIN (OVA) INTO MACROPHAGES VIA Fc/FcR INTERACTION WITH ANTI-GAL ON THE LIPOSOMES

12 SIINFEKL SPECIFIC CD8+ T CELLS (ELISPOT) AND ANTI-OVA ANTIBODIES (ELISA) IN GT-KO MICE OR WILD TYPE (WT) MICE IMMUNIZED WITH OVA ENCAPSULATED IN  -GAL LIPOSOMES ANTI-OVA ANTIBODIES IN SERUM GT KO mice WT mice GT KO miceWT mice SIINFEKL specific CD8+ T cells Abdel-motal U et al. VACCINE 27: 3072-3082, 2009.

13 MACROPHAGE T cell T cell receptor UPTAKE OF Flu VIRUS (PR8) ENGINEERED TO EXPRESS  -GAL EPITOPES INTO MACROPHAGES VIA Fc/FcR INTERACTION WITH ANTI-GAL ON THE VIRUS Flu virus (PR8) NA HA Anti-Gal Flu virus peptides

14 ANTI-FLU VIRUS ANTIBODY FORMATION AND PROTECTION AGAINST PR8 FLU VIRUS CHALLENGE FOLLOWING IMMUNIZAITON WITH FLU (  ) OR  -GAL FLU VIRUS (  ) ANTI-FLU VIRUS ANTIBODY (ELISA) SURVIVAL AFTER FLU CHALLENGE Abdel-motal U et al. J. Virol. 81: 9131-9141. 2007..

15 Interaction of flu virus and of anti-Gal antibody with  -gal/SA liposomes peptide MHC

16 COLLABORATIONS Ussama Abdel-motal Kim Wigglesworth Heath Guay Raymond Welsh


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