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Draft proposal and concept for malarial vaccine.

Draft proposal and concept for malarial vaccine. Basic concept for vaccines. R eachable target Ag Inhibition of targets can block the life cycle of parasites The target has high immunogenic capability to stimulate immune responses High ratio of Ab : target Ag

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Draft proposal and concept for malarial vaccine.

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  1. Draft proposal and concept for malarial vaccine.

  2. Basic concept for vaccines • Reachable target Ag • Inhibition of targets can block the life cycle of parasites • The target has high immunogenic capability to stimulate immune responses • High ratio of Ab : target Ag • Enough titer to inactivate the target • Target parasite stage at the lowest density • Could be maintained at high effective titer for protection

  3. REACHABLE TARGETS

  4. Reachable target: Surface Ag • Available in body fluid • Not in erithrocytes • Position at the surface of parasites Antibody bind to the surface protein of a sporozoite

  5. BLOCKING THE LIFE CYCLE

  6. Life cycle of Plasmodium parasites Sporozoites In salivary glands Sporozoites Schizon Merozoite Merozoite Fertilization In mid-gut Sporozoites In tissue RBC stage Gamet Liver stage Tropozoite Oocysts In mid-gut

  7. Blocking the parasites Sporozoites In salivary glands Adult Sporozoites Schizon Merozoite Merozoite Fertilization In mid-gut Sporozoites In tissue RBC stage Gamet Liver stage Tropozoite Larva Eggs Oocysts In mid-gut VECTOR CONTROL BLOCKING ENTERIC STAGE IN MOSQUITO DRUGS AND VACCINATION IN HUMAN

  8. Study plans? • Adult mosquito target: Transmission-blocking Ab for the enteric stage of parasites: • Ab againtsgametocyites and oocyst ready in infected blood, • Ab against mosquito intestinal cell’s surface protein. • Larval mosquito target: the IgY antibodies from chicken egg yolk targeting larval enteric cell or larval nature enteric bacteria • Human target: Optimize sporozoite-based vaccine with regular booster to get high ratio of Ab: Ag target

  9. Blocking the parasites Sporozoites In salivary glands Adult Sporozoites Fertilization In mid-gut RBC stage Gamet Liver stage Larva Eggs Oocysts In mid-gut Chicken Egg Yolk IgY as a larvacide Ab to gametocytes or oocyst ready in patient blood Surface sporozoite Ag-based vaccine with regular booster

  10. IMMUNOGENIC ANTIGENS

  11. What factor influence the immunogenic nature of an antigen? • Substance contents of the Ag: LPS, protein, Nucleic acid? • 3D Structures of the Ag? • Adjuvant?

  12. HIGH RATIO OF AB : TARGET AG

  13. Dynamic of parasites in the life cyclethat could be a vaccine target Reserve concentration when the Ab target the weakest points of parasite’s population, 100 - 103 Minimum Level of Ab needed to inactivate 1012 parasites during erythrocytic cycles Different parasite’s concentration =1012 - 103 Sporozoite in Salivary gland and other tissue of mosquitoes Erythrocyte stages in human blood Mosquito bite Sporozoite injected Mosquito bite Gametocytes transmitted Oocyst developed Mosquito bite Sporozoite injected Conventional vaccine’s target Alternative vaccine’s target in mosquitoes Alternative vaccine’s target in human Alternative vaccine’s target in human

  14. MAINTAIN THE HIGH TITER AB IN BLOOD

  15. Prevalence Ab terhadap surface Ag sporozoitmenurutkelompokumurpadadaerah low transmission area dan high transmission area. Titer yang tinggipadasemuakelompokumurhanyapadadaerah high transmission area menunjukkanperlunya booster regular vaksinsporozoit yang diaplikasikanuntukmenjamintingkatproteksi.

  16. REGULAR VACCINATION BOOSTERMAY MIMIC THE HIGH TRANSMISSION AREA EFFECTS TO BLOOD TITER OF THE ANTIBODY AGAINST THE ANTIGEN

  17. Dynamic of parasites in the life cyclethat could be a vaccine target Reserve concentration when the Ab target the weakest points of parasite’s population, 100 - 103 Minimum Level of Ab needed to inactivate 1012 parasites during erythrocytic cycles High ratio of Ab:Ag target can be maintained with regular vaccination booster (e.g. every 6 months) Different parasite’s concentration =1012 - 103 Sporozoite in Salivary gland and other tissue of mosquitoes Erythrocyte stages in human blood Mosquito bite Sporozoite injected Mosquito bite Gametocytes transmitted Oocyst developed Mosquito bite Sporozoite injected

  18. WHAT IS THE STRATEGY • Adult peoples in high transmission area usually have enough protective immunity to malaria parasites and show less clinical symptoms. No need for vaccines? • Neonatus and children in high transmission area my have more risk to get severe malaria since they have only have low titer of Ab, hence need to get early vaccination with regular booster • Peoples in low transmission area may need early vaccination with regular booster too • Susceptible peoples that visit in to an endemic area may need: • Vaccination 3 month prior to long visit (e.g. 1-2 year) • Get vaccination booster every 6 month during in the area • If plan to have regular visit, same regular booster needed

  19. TESTING THE VACCINE CANDIDATE

  20. Molecular design and analysisCell-based assayAnimal experimentClinical trial

  21. Teman2 yang punyaideberkaitandenganpetasubjekpenelitianini, silahkanmembuat draft proposal 2-3 halamandandikirimkankesemua email yang tercantum (replay all) agar bisakitadiskusikan.

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