malaria vaccines

Question 1

What combination of pharmocological and other interventions are currently used to control malaria?

Answer 1

anti- malarials
nets
insecticides.

Question 2

4 stages of lifecylce that antibodies can target?

Answer 2

• Neutralise sporozoite infection of hepactocytes.
• Prevent merozoite infection of blood cells
• prevent infected RBC pathology (cytoadherence)

Inhibit sexual development in the midgut of mosquitos.

Question 3

What stage does CD8 T cell responses target?

Answer 3

the hepatocyte infection stage.

Question 4

What are the two main vaccination strategies that are used?

Answer 4

Irradiated/ genetically attenuated sporozoites.

subunit vaccines targeting antigens of a specific stage.

Question 5

What are the 4 challenges that face malaria vaccines?

Answer 5

complex lifecycle
Generating an immune response against the diversity of parasites.
unknown what a protective immune response looks like.
Technological issues- generating a high enough immune response.

Question 6

3 different ways to infect people wiht malaria in challenge trials? (controlled human malarial infection)

Answer 6

1. with mosquito bites
2. inject with cryopreserved sporozoites
3. innoculate blood-stage parasites IV.

Question 7

What does PMR and LBI stand for and mean?

Answer 7

parasite multiplication rate (in blood)

LBI liver to blood inoculum (how many produced in blood from liver)

Question 8

what is the PfSPZ vaccine?

Answer 8

mosquitos are irradiated and the sporozoites are taken and cryopreserved.
Administered via IV (subcutaneous not effective) and sporozoites can invade hepactoyctes but aren’t productive.

Question 9

What are the disadvantages of the PfSPZ vaccine?

Answer 9

Requires alot of manpower to extract sporozoites,.
Protection against diverse plasmodium difficult.
No efficacy in kenyan infants- thought to be due to underdeveloped ydelta T cells.

Question 10

What adjuvant is used for the RTS,S vaccine?

What platform is used and what antigen is targeted?

Answer 10

AS01 (GSK adjuvant)

The sporozoite surface antigen reombinant CSP is expressed on a hep viral vector.

Question 11

Whats the efficacy of the RTS,S vaccine and how might it be improved?

Answer 11

around 30% might improve with CSP expressed all over the virion.
Or by designing vaccines inducing responses aginst the junctional epitope of CSP.

Question 12

What vaccine platform and liver stage antigen is targeted in liver-stage vaccine?

Answer 12

Chimpanzee adenovirus vector expressing the hepatocyte stage antigen MeTRAP.
Then heterologous prime boost with MVA MeTRAP.

Question 13

How might liver stage vaccines be improved?

Answer 13

In combination with RTS,S vaccine.

Or with prime target boost with IM and then IV administration to boost liver immune response.

Question 14

4 antigens that can be Ab targets in the sexual and mosquito stages?

Answer 14

sexual gametoctyes: Pfs48/45. Pfs230C

mosquito: Pfs25 and Pfs28.

Question 15

How does the standard membrane feeding assay work?

Answer 15

Put ab and blood with mosquitos separated with membrane feeder, and then count oocysts that form in midgut.

Question 16

Which gametocyte stage antigens gave best results?

Answer 16

Pfs230C and Pfs25/

Question 17

Two antigens that are targeted on the merozoites to inhibit red blood cell invasion that wasn’t efficacious??

Answer 17

merozoite MSP1 surface protein, and AMA1 (important for tight junction formation).

Question 18

What interaction is essential and non-redundant for P. falciparum RBC infection?

Answer 18

RH5 and basigin (receptor on RBC). RH5 is highly conserved.

Question 19

What vaccine platform induces greatest antibody response?

Answer 19

subunit vaccines (not peptide ones, ones that retain native protein confirmation).

Question 20

What was found to be a good correlate for protection in RH5 vaccines?

Answer 20

the results from growth inhibition activity assay.

Question 21

Where are the critical epitopes on RH5 targeted by AB?

Answer 21

near the diamond tip within or close to the basagin binding site of RH5.

Question 22

what is the attraction of viral-like particles?

Answer 22

Thought to improve Ab induction because of improved BCR clustering.

Question 23

What technique for viral-like particles have they used for RH5?

Answer 23

Used a hep B- viral-like protein with spy catcher that is added to RH5 protein with SpyTag that forms strong covalent bonds.

Question 24

Issues with investigating vaccines for P. vivax?

Answer 24

There’s no long term in vitro culture system and they under hyponozoites.

Question 25

What is the P. vivax equivalent of the RH5-basigin interaction?

Answer 25

Duffy binding protein (DBP)- duffy antigen.

Populations exist which lack this aren’t infected by p vivax.