Vl 7 Plasmodium I Flashcards
Describe the journey of the Plasmodium sporozoite from the mosquito bite to the liver.
1) mosquito injects sporozoite to skin
2) travel to blood vessels
3) travel with blood stream to the liver
4) pass through Kupffer cells to enter one of the hepatocytes with assistance of the apical complex
5) binds to HSPGs with CS-protein and TRAP, wanders through some and spontaneously settles down in one to convert into shizont stage and proliferate into millions of merozoites (same invasion strategy as Toxoplasma)
How do Plasmodium sporozoites move?
- have circular movement (cork screw) in the approximate diameter of blood vessels and have same gliding motility as Toxoplasma (actin-myosin mediated) with CS-protein help
Why is the Plasmodium sporozoite stage relevant for vaccine development?
- infective stage for humans
- good target to kill the parasites before they enter the liver to replicate
What is the molecular basis of the RTS,S/ASO1 anti-malaria vaccine candidate?
- Circumsporozoite protein is targeted during sporozoite invasion to block it from infecting the liver
- the vaccine consists of adjuvants to increase the immune response, combined with hepatitis B viral proteins and genes from the repeat and B- + T-cell epitopes in the CSP of the parasite
What is the present efficacy of the phase III trials of the the RTS,S/ASO1 anti-malaria vaccine candidate? Explain.
- vaccinations of newborns: first 3 years 65% efficient
- children above 4 years: only 30% efficient
⇒ dosage is not effective and vaccine is not effective enough, especially in older children - high antibody titers not enough
- 100% needed (every liver stage produces x-times blood stage)
Describe the cellular functions of Plasmodium circumsporozoite protein
- surface protein ⇒ secreted from rhoptries and micronemes
- essential for the gliding motility and adhesion to the epithelium of mosquito salivary glands
- helps surviving in macrophages by ribo-toxic activity to inhibit protein synthesis in host cells
