Apr/28/09 Feng, Chi wei Supervised by Prof. Ching Tsan Huang, PhD - PowerPoint PPT Presentation

Nature Chemical Biology 4 , 238 ‐ 240 (2008) Faustin Kamena, Marco Tamborrini, Xinyu Liu, Yong ‐ Uk Kwon, Fiona Thompson, Gerd Pluschke &Peter H Seeberger Apr/28/09 Feng, Chi ‐ wei Supervised by Prof. Ching ‐ Tsan Huang, PhD 1

� 41% of the world's population � 350–500 million cases of malaria reported worldwide each year � over one million people die � 2 deaths per minute in severe areas � The 4th cause of death in children in several developing countries 2

Europe Africa 3

� Glycosylphosphatidylinositol ( GPI ) as a Candidate Louis Schofield et al. Synthetic GPI as a candidate anti ‐ toxic vaccine in a model of malaria Nature 418 , 785 ‐ 789 4

Naturally acquired GPI Purified by HPLC Dissolved in Methanol ELISA ‐ based Analysis 5

� In Research, � Natural GPI only in Minute Amount � Impurity Removability leads to Sample Loss contradictory results appear… Infected v. Uninfected � Anti ‐ GPI Immune Response v. Malarial Exposure ? 6

� DNA array • cDNA • Oligonucleotides � Glycan array • Carbohydrates or glycosides 7

• Favor small sample size • Rapid • High throughput • Exploit genome data • Quantitative analysis 8

Abundant scanty By courtesy of XZ Song et al 9

M3 M3E M4 M4E 10

7 glycans per unit X 64 units per chip 448 spots on a chip for further analysis 11

Con A: Concanavalin A as a lectin Linear Correlation between conc of Man4 ‐ GPI and ConA 12

Is GPI immune response depending on the length of the molecule? 13

6 individuals from malarial epidemic region of Ghana, and their sera containing anti ‐ GPI IgG 14

M3 Naturally produced in Blood ‐ stage of Plasmodium falciparum M3E M4E M4 15

What are the roles of Mannose and EtNH2 in immune response? 16

Higher mean value Man4 ‐ GPI Man3 ‐ GPI EtNH 2 might not M3 M3E M4 M4E be critical Binding ability test by IgG from sera samples of malria ‐ exposured donors 17

What is the pattern for Europeans in non ‐ malarial epidemic regions? 18

Man4 ‐ GPI response is more general among some nonmalarial species Man3 ‐ GPI response is more specific to malaria M3 M3E M4 M4E Binding ability test by IgG from sera samples of Non ‐ malaria exposured 19 donors

Since the Man4 ‐ GPI is more general while the Man3 ‐ GPI more specific to malaria, for a given area… Anti ‐ Man3 ‐ Extent to GPI Antibody which malaria Anti ‐ Man4 ‐ rages GPI Antibody 20

Any strategical hints for vaccine developments? 21

Malarial sporozoite challenge trial on volunteers residing in nonmalarial ‐ exposed Europe Both Man3 ‐ GPI and Man4 ‐ GPI responses were increased M3 M3E M4 M4E 22

Glycan array GPI immune response is length ‐ dependent GPI Synthetic GPI Man3 ‐ GPI is more specific The 4 th to malarial Mannose parasites as a key element Non ‐ Malarial Exposure Malarial Exposure Vaccine against Man3 ‐ GPI of Correlation of anti ‐ GPI malarial response to malarial early stage exposure 23

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