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.

Slides:

Advertisements

Similar presentations

CD40L concentration-dependently binds to Mac-1's I-domain. Wolf D et al. Circulation Research 2011;109: Copyright © American Heart Association.

Advertisements

Fc Receptors Oct. 28, 2009 Extra reading on web Daniel Conrad 423 MSB, I. CD23.

Understanding biology through structuresCourse work 2006 Understanding Immune Recognition.

Chapter15 B cell mediated immune response. B cells mediated immune response Humoral immunity(HI) or antibody mediated immunity: The total immunological.

IL-2 as the adjuvant in FMD vaccine Chunxia su ， ph.D. Ningxia Medical University Yinchuan ， China.

Defenses Against Infection 1. Innate responses (humoral and cellular) 2. Immunity to intracellular pathogens NK cells, control of Th1/Th2 responses 3.

Pattern recognition in the immune system. Specific peptide recognition Antibody epitopes T-cell receptors recognizing peptides presented on MHC-molecules.

Epitope Selection Rational Vaccine design. Why? Therapeutic vaccines Therapeutic vaccines Treatment of viral infections (e.g., HIV, HCV), and resistant.

Immunology Chapter 16, Lecture 2 Richard L. Myers, Ph.D. Department of Biology Southwest Missouri State Temple Hall 227 Telephone:

Antibody Fab region bound to a sequential antigen

P.K.Shah, MD Director, Division of Cardiology and Atherosclerosis Research Center Cedars Sinai Medical Center, Los Angeles “Immunomodulation of Atherosclerosis”

DIAGNOSTIC IMMUNOLOGY

Lecture 14 Immunology: Adaptive Immunity. Principles of Immunity Naturally Acquired Immunity- happens through normal events Artificially Acquired Immunity-

Chapter 15 B cell mediated immune response. B Cells Lymphocytes that react directly with antigens Require stimulation from Helper T Cells Offspring become.

Overview of Immunology Organs and tissues Cells Molecules Components of IS Functions of IS Pathology of IR * IS: Immune system IR: Immune response Applications.

Adaptive/Acquired Immunity

Lecture #10 Aims Describe T cell maturation and be able to differentiate naïve and effector T cells. Differentiate the development and functions of Th1.

Humoral Immune Effector Mechanisms. Ig of Different Isotypes How do the functional differences impact the immune response ? The focus will be on Ig and.

The Immune System Dr. Jena Hamra.

Modular Nanodevices for Creation of Smart Adaptable Vaccine Delivery Vehicles Tarek M. Fahmy Dept. of Biomedical Engineering, Yale University Several key.

University of Ishik Faculty of dentistry Practical Medical Physiology

BME 301 Lecture Eight. Review of Lecture 7 Science “Science is the human activity of seeking natural explanations for what we observe in the world around.

Components of the Immune System.

COMPLEMENT SYSTEM. The complement system is a set of plasma proteins that act in a cascade to attack and kill extracellular pathogens. Most of the complement.

Monocytes in Immune Defense & Cell-mediated Cytotoxicity Pin Ling ( 凌斌 ), Ph.D. ext 5632; References: 1. Male D., J. Brostoff,

Interferons Induction of synthesis Induction of antiviral activity Antiviral activities induced by interferons  and  Antiviral activities induced by.

CD47 modulates the phagocytic clearance and replication of Plasmodium yoelii malaria parasite Rajdeep Banerjee 1, Sanjay Khandelwal 2, Yukiko Kozakai 1,

Richard C. Chou, Nancy D. Kim, Christian D. Sadik, Edward Seung, Yinan Lan, Michael H. Byrne, Bodduluri Haribabu, Yoichiro Iwakura, Andrew D. Luster Lipid-Cytokine-Chemokine.

Lecture Outline Antigens Definition Exogenous Endogenous

Life and Death of CD8 T Cells: A Role of IL-12

Atezolizumab Drugbank ID : DB11595.

Immunology Ch Microbiology.

Avoiding Immune Detection

Figure 1 CTLA-4 and PD-1–PD-L1 immune checkpoints

The Major Histocompatibility Complex (MHC)

Immunological memory Topics Immune regulation  T cells

Loss of Extracellular Superoxide Dismutase Induces Severe IL-23-Mediated Skin Inflammation in Mice Yun Sang Lee, In-Su Cheon, Byung-Hak Kim, Myung-Ja.

Immunology Cell Volume 100, Issue 1, Pages (January 2000)

BIOE 301 Lecture Eight.

Volume 24, Issue 11, Pages (November 2016)

Chapter 13 Effector Responses

Figure 4 Macrophage-targeting antitumour treatment approaches

Figure 2 Emerging models of antibody-mediated rejection (ABMR) and

Volume 22, Issue 7, Pages (July 2014)

Fig. 5 A competent Fc is required for the antitumor immune response.

Host Defence Peptides B cell

Type 1 immunity drives metabolic disease but protects against NAFLD

Volume 10, Issue 9, Pages (March 2015)

Mechanism of CTLA-4-induced immunosuppression.

Volume 25, Issue 4, Pages (April 2017)

LV activation of DCs and subsequent CD8+ T cell priming are dependent on STING and cGAS but not on MyD88, TRIF, or MAVS. LV activation of DCs and subsequent.

Volume 22, Issue 6, Pages (February 2018)

Development of Effective Vaccines against Pandemic Influenza

Matthew Charles Woodruff, Eui Ho Kim, Wei Luo, Bali Pulendran

Th1 and Th2 immune responses

Overview of the Immune System

Volume 29, Issue 6, Pages (June 2016)

Fig. 5 Treatment with an OX40 agonist antibody of 3-week-old HBVtgRag−/− mice or mice with chronic HBV disease results in an altered immune response to.

Antigen-specific immune responses are enhanced in hypertension.

The arsenal of virulence factors expressed by GAS to thwart the host innate immune response. The arsenal of virulence factors expressed by GAS to thwart.

Alterations in epithelial permeability of the intestines of mice lacking afadin, nectin-2 and nectin-3. Alterations in epithelial permeability of the intestines.

A schematic presentation of secreted, endocytic, and signaling pattern-recognition receptors. A schematic presentation of secreted, endocytic, and signaling.

Mice immunized twice with RRBC showed superior protection to tumor challenge with αGal-positive MC38 colon carcinoma cells compared with mock-immunized.

Both the MMP9 and MMP2 systems are activated by anti-Aβ antibodies, IVIg, and mouse IgG. Both the MMP9 and MMP2 systems are activated by anti-Aβ antibodies,

MDSC-derived IL-6 enhances tumor progression through the inhibition of tumor-specific TH1 development and of their helper activity for CD8+ T cells. MDSC-derived.

TLR9 deficiency leads to more severe impairment of endothelium-dependent vasorelaxation and promotes aberrant B cell phenotype in imiquimod-induced autoimmunity.

Antigen presenting cell قسم تقنيات التحليلات المرضية

Varying the MHC-I affinity, TCR affinity or antigen dose alters the phenotype of CD8 T cells ex vivo. Varying the MHC-I affinity, TCR affinity or antigen.

Design and operation of p.DOM-epitope vaccines.

Presentation transcript:

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

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

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

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

 -gal/SA liposome

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

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

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: , 2010

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)

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

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

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: , 2009.

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

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:

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

COLLABORATIONS Ussama Abdel-motal Kim Wigglesworth Heath Guay Raymond Welsh