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Cooperation is Required for
Schistosomiasis Vaccine Production
       and Implementation

               Rashika El Ridi
  Zoology Department, Faculty of Science,
            Cairo University
What is Schistosomiasis? Also named Snail
     Fever, Bilharzia or Bilharziasis

      A disease, very often of
children, caused by the platyhelminth
  parasite of the genus Schistosoma
The Infective Stage: The Cercaria
 Coming out of an Infected Snail
Adult Schistosomes
In the Host Vasculature, Schistosome Pairs
      Deposit Hundreds of Eggs Daily
The Granuloma
Geographical Distribution of Schistosomiasis
blue: S. mansoni; green: S. haematobium; red: S. japonicum
          orange: S. mansoni and S. haematobium
Besides affecting 500 million people and 800
million, mostly children, at risk of the
infection, schistosomiasis deviates the host
immune system towards a polarized T helper
(Th) 2 environment, thus rendering the affected
human highly susceptible to cancer development
and to infection with acquired immuno-
deficiency (HIV) and hepatic (namely HCV)
virus, Mycobacterium tuberculosis, and
malaria, afflictions all requiring a strong Th1
immune environment for control and resistance.
The Only Drug Available:
     Praziquantel
The disease may be
eradicated via elimination of
transmission if an effective
vaccine is available. Many
roadblocks hindered the
development of such vaccine.
We needed to identify the correct
parasite antigen (s) for use in
vaccination.

We needed to identify the
mechanism(s) by which the
immune system of the host may
attack the parasite.
A- Parasite Antigen(s) Selection

  We have identified the correct parasite
  vaccine candidate antigens, the larval
  excretory-secretory products
  (ESP), namely glutathione-S-
  transferase (GST), enolase, triose-
  phosphate-isomerase
  (TPI), glyceraldehyde 3-phosphate
  dehydrogenase, and 2 cys-
  peroxyredoxin (thioredoxin peroxidase)
B- The Most Plausible
Mechanism(s) of Protective
       Immunity
  The Hunt in the Pulmonary
         Capillaries
How would then the Host Immune
    Effectors Attack the Parasite?
• They do not directly kill it. They
  PURSUE, HUNT it in the tight capillaries of
  the lung vasculature.
The Most Plausible Mechanism(s) of
      Protective Immunity
 The Hunt of Larvae in the Pulmonary Capillaries
          by the Host Immune Effectors:
IFN-g-activated macrophage release of NO and H2O2

IL-17-mediated neutrophils recruitment and the efficiency of
   neutrophils extracellular trap

IL-4-and IL-13-and ESP/Antibody-activated basophils release of
   histamine and its effects of the capillary endothelium
   permeability

IL-4-and IL-5-and ESP/Antibody-activated eosinophils release of
   toxic basic proteins, the most powerful effectors of parasite
   attrition.
We have been
able to render the
hunt as effective
as possible, via
using the correct
adjuvant
50


                                                         45


                                                         40




                    Individual mouse total worm burden
                                                         35


                                                         30


                                                         25


                                                         20


                                                         15


                                                         10


                                                          5


                                                          0
                                                              Inf/Controls   IL-25/Mix IL-33/Mix     IL-25       IL-33/Controls

Mean + SE                                                       37.5 + 2.3 12.1 + 1.2   8.5 + 0.9   27.2 + 2.7    20.5 + 2.9
P and reduction                                                            <0.0001      <0.0001      0.0145        0.0007
(versus Inf/Controls)                                                       67.63%      77.33%       27.46%       45.33%
P and reduction                                                            <0.0001       0.0033
(versus cytokine Controls)                                                   55.51%      58.53%
We are further improving the selection of larval
  excretory-secretory candidate vaccine
  antigens, singly or in a mixture,
and the immunization regimen, namely antigen and
  Type-2 adjuvant dose, injection site and schedule,
And we may likely reach a sterilizing vaccine for
  schistosomiasis in a near future.


Cooperation is required for independent
 experiments, pre- and clinical
 studies, and production and
 implementation of the vaccine
Collaborators
            Dr. Hatem Tallima
            (Ph. D.)
            and
            Mr. Abdel Badih Foda

            And the Theodore
            Bilharz
            Research Institute Team
            at the Schistosome
            Biological Supply
THANK YOU   Program

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Cooperation is Required for Schistosomiasis Vaccine Production and Implementation [Rashika EL-Ridi, L’Oréal-UNESCO Laureate 2010, Egypt]

  • 1. Cooperation is Required for Schistosomiasis Vaccine Production and Implementation Rashika El Ridi Zoology Department, Faculty of Science, Cairo University
  • 2. What is Schistosomiasis? Also named Snail Fever, Bilharzia or Bilharziasis A disease, very often of children, caused by the platyhelminth parasite of the genus Schistosoma
  • 3. The Infective Stage: The Cercaria Coming out of an Infected Snail
  • 5.
  • 6. In the Host Vasculature, Schistosome Pairs Deposit Hundreds of Eggs Daily
  • 8. Geographical Distribution of Schistosomiasis blue: S. mansoni; green: S. haematobium; red: S. japonicum orange: S. mansoni and S. haematobium
  • 9.
  • 10. Besides affecting 500 million people and 800 million, mostly children, at risk of the infection, schistosomiasis deviates the host immune system towards a polarized T helper (Th) 2 environment, thus rendering the affected human highly susceptible to cancer development and to infection with acquired immuno- deficiency (HIV) and hepatic (namely HCV) virus, Mycobacterium tuberculosis, and malaria, afflictions all requiring a strong Th1 immune environment for control and resistance.
  • 11. The Only Drug Available: Praziquantel
  • 12. The disease may be eradicated via elimination of transmission if an effective vaccine is available. Many roadblocks hindered the development of such vaccine.
  • 13. We needed to identify the correct parasite antigen (s) for use in vaccination. We needed to identify the mechanism(s) by which the immune system of the host may attack the parasite.
  • 14. A- Parasite Antigen(s) Selection We have identified the correct parasite vaccine candidate antigens, the larval excretory-secretory products (ESP), namely glutathione-S- transferase (GST), enolase, triose- phosphate-isomerase (TPI), glyceraldehyde 3-phosphate dehydrogenase, and 2 cys- peroxyredoxin (thioredoxin peroxidase)
  • 15. B- The Most Plausible Mechanism(s) of Protective Immunity The Hunt in the Pulmonary Capillaries
  • 16. How would then the Host Immune Effectors Attack the Parasite? • They do not directly kill it. They PURSUE, HUNT it in the tight capillaries of the lung vasculature.
  • 17. The Most Plausible Mechanism(s) of Protective Immunity The Hunt of Larvae in the Pulmonary Capillaries by the Host Immune Effectors: IFN-g-activated macrophage release of NO and H2O2 IL-17-mediated neutrophils recruitment and the efficiency of neutrophils extracellular trap IL-4-and IL-13-and ESP/Antibody-activated basophils release of histamine and its effects of the capillary endothelium permeability IL-4-and IL-5-and ESP/Antibody-activated eosinophils release of toxic basic proteins, the most powerful effectors of parasite attrition.
  • 18.
  • 19.
  • 20.
  • 21. We have been able to render the hunt as effective as possible, via using the correct adjuvant
  • 22.
  • 23. 50 45 40 Individual mouse total worm burden 35 30 25 20 15 10 5 0 Inf/Controls IL-25/Mix IL-33/Mix IL-25 IL-33/Controls Mean + SE 37.5 + 2.3 12.1 + 1.2 8.5 + 0.9 27.2 + 2.7 20.5 + 2.9 P and reduction <0.0001 <0.0001 0.0145 0.0007 (versus Inf/Controls) 67.63% 77.33% 27.46% 45.33% P and reduction <0.0001 0.0033 (versus cytokine Controls) 55.51% 58.53%
  • 24. We are further improving the selection of larval excretory-secretory candidate vaccine antigens, singly or in a mixture, and the immunization regimen, namely antigen and Type-2 adjuvant dose, injection site and schedule, And we may likely reach a sterilizing vaccine for schistosomiasis in a near future. Cooperation is required for independent experiments, pre- and clinical studies, and production and implementation of the vaccine
  • 25. Collaborators Dr. Hatem Tallima (Ph. D.) and Mr. Abdel Badih Foda And the Theodore Bilharz Research Institute Team at the Schistosome Biological Supply THANK YOU Program