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Draft proposal and concept for malarial
vaccine.
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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
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REACHABLE TARGETS
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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
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BLOCKING THE LIFE CYCLE
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Life cycle of Plasmodium parasites
Sporozoites
Liver stage
RBC stage
Tropozoite
Merozoite Schizon
GametFertilizationIn mid-gut
OocystsIn mid-gut
Sporozoites In salivary glands
SporozoitesIn tissue
Merozoite
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Blocking the parasites
Sporozoites
Liver stage
RBC stage
Tropozoite
Merozoite Schizon
GametFertilizationIn mid-gut
OocystsIn mid-gut
Sporozoites In salivary
glands
SporozoitesIn tissue
Merozoite
Adult
Larva Eggs
DRUGS AND VACCINATIONIN HUMAN
BLOCKING ENTERIC STAGE IN MOSQUITO
VECTOR CONTROL
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Study plans?
• Adult mosquito target: Transmission-blocking Ab for the enteric stage of parasites:
• Ab againts gametocyites 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
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Blocking the parasites
Sporozoites
Liver stage
RBC stage
Gamet FertilizationIn mid-gut
OocystsIn mid-gut
Sporozoites In salivary
glands Adult
Larva Eggs
Surface sporozoite Ag-based vaccine with regular
booster
Ab to gametocytes or oocyst ready in patient
blood
Chicken Egg Yolk IgY as a larvacide
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IMMUNOGENIC ANTIGENS
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What factor influence the immunogenic nature of an antigen?
• Substance contents of the Ag: LPS, protein, Nucleic acid?• 3D Structures of the Ag?• Adjuvant?
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HIGH RATIO OF AB : TARGET AG
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Dynamic of parasites in the life cyclethat could be a vaccine target
Mosquito biteSporozoite
injected
Mosquito biteGametocytes transmitted
Oocyst developed
Mosquito biteSporozoite
injected
Erythrocyte stages in human
blood
Sporozoite in Salivary gland and
other tissue of mosquitoes
Minimum Level of Ab needed to inactivate 1012 parasites during erythrocytic cycles
Reserve concentration when the Ab target the weakest points of parasite’s population, 100 - 103
Conventional vaccine’s target
Alternative vaccine’s target in mosquitoes
Alternative vaccine’s target
in human
Alternative vaccine’s target
in human
Different parasite’s concentration =1012 - 103
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MAINTAIN THE HIGH TITER AB IN BLOOD
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Prevalence Ab terhadap surface Ag sporozoit menurut kelompok umur pada daerah low transmission area dan high transmission area. Titer yang tinggi pada semua kelompok umur hanya pada daerah high transmission area menunjukkan perlunya booster regular vaksin sporozoit yang diaplikasikan untuk menjamin tingkat proteksi.
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REGULAR VACCINATION BOOSTER
MAY MIMIC THE HIGH TRANSMISSION AREA EFFECTS TO BLOOD TITER OF THE ANTIBODY
AGAINST THE ANTIGEN
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Dynamic of parasites in the life cyclethat could be a vaccine target
Mosquito biteSporozoite
injected
Mosquito biteGametocytes transmitted
Oocyst developed
Mosquito biteSporozoite
injected
Erythrocyte stages in human
blood
Sporozoite in Salivary gland and
other tissue of mosquitoes
Minimum Level of Ab needed to inactivate 1012 parasites during erythrocytic cycles
Reserve concentration when the Ab target the weakest points of parasite’s population, 100 - 103
Different parasite’s concentration =1012 - 103
High ratio of Ab:Ag target can be maintained with regular vaccination
booster (e.g. every 6 months)
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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
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TESTING THE VACCINE CANDIDATE
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Molecular design and analysisCell-based assay
Animal experimentClinical trial
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Teman2 yang punya ide berkaitan dengan peta subjek penelitian ini, silahkan membuat draft proposal 2-3 halaman dan dikirimkan kesemua email yang tercantum (replay all) agar bisa kita diskusikan.