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

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

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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%

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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

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41% of the world's population 350–500 million cases of malaria reported

worldwide each year

  • ver one million people die

2 deaths per minute in severe areas The 4th cause of death in children in several

developing countries

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Europe Africa

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Glycosylphosphatidylinositol (GPI) as a Candidate

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Louis Schofield et al. Synthetic GPI as a candidate anti‐ toxic vaccine in a model of malaria Nature 418, 785‐789

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

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In Research,

Natural GPI only in Minute Amount Impurity Removability leads to Sample Loss

contradictory results appear…

Anti‐GPI Immune Response v. Malarial

Exposure?

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Uninfected Infected v.

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DNA array

  • cDNA
  • Oligonucleotides

Glycan array

  • Carbohydrates or

glycosides

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  • Favor small sample size
  • Rapid
  • High throughput
  • Exploit genome data
  • Quantitative analysis
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By courtesy of XZ Song et al

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scanty Abundant

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M3E M4E M3 M4

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

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Linear Correlation between conc of Man4‐GPI and ConA

Con A: Concanavalin A as a lectin

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

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

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M3 M3E M4E M4 Naturally produced in Blood‐stage

  • f Plasmodium falciparum
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What are the roles of Mannose and EtNH2 in immune response?

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M3 M3E M4 M4E Higher mean value

Man4‐GPI Man3‐GPI

Binding ability test by IgG from sera samples of malria‐exposured donors

EtNH2 might not be critical

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

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M3 M3E M4 M4E Binding ability test by IgG from sera samples of Non‐malaria exposured donors

Man4‐GPI response is more general among some nonmalarial species Man3‐GPI response is more specific to malaria

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Since the Man4‐GPI is more general while the Man3‐GPI more specific to malaria, for a given area…

Anti‐Man3‐ GPI Antibody Anti‐Man4‐ GPI Antibody Extent to which malaria rages

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Any strategical hints for vaccine developments?

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M3 M3E M4 M4E

Malarial sporozoite challenge trial on volunteers residing in nonmalarial‐exposed Europe

Both Man3‐GPI and Man4‐GPI responses were increased

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23 GPI immune response is length‐dependent

The 4th Mannose as a key element

Malarial Exposure

Man3‐GPI is more specific to malarial parasites

Non‐Malarial Exposure

Vaccine against Man3‐GPI of malarial early stage GPI Correlation of anti‐GPI response to malarial exposure

Glycan array Synthetic GPI

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