L19- Parasite vaccines Flashcards
What kind of vaccines can you give?
- Live vaccine
- Attenuated vaccine
- Dead vaccine
- Extract
- Purified antigens
- Recombinant antigens
- DNA vaccines
What was the first parasite vaccine against?
Against lungworm in cattle- Dictyocaulus vivparus
Causes Husk-> major problem in farming industry
What is life cycle of Dictyocaulus vivparus?
lung worm in cattle
- Adult worms in lungs
- Eggs hatch in host to release L1s.
- Pass out with host faeces
- Moult twice in external environment to infective L3.
- Ingested by host when feeding.
- Penetrate mucosa.
- Moult to L4 in lymph nodes.
- Pass via lymph to lungs,
- Moult to juvenile.
- Adult worms in lungs.
How was the dictyocaulus vivparus vaccine developed?
In Glasgow 1960s.
Carried out work using irradiated L3 larvae.
These do not complete the full life cycle- they are infective but only grow to L4 stage then die before they reach the lungs. (attenuated the larvae by giving them large doses of radiation)
Used guinea pig as model-> showed it worked.
Summarise how taeneids (genus of tapeworms, fo which some infect humans) affect the livestock industry
Get oncospheres hatching in gut and penetrate mucosa and go to viscera in intermediate host.
Get meat with tapeworms in.
What was found about vaccines for tapeworms?
Taeneids
Animal mode- Taenia taenaeformis in rodents. And this showed we could make animals immune to it and this immunity is antibody mediated.
The target of the immunity is the oncosphere. This is great because it if before it gets to the muscle.
Immunity can also be achieved by injecting oncosphere antigens alone, don’t need the whole live organism.
Describe briefly the Taenia tapeworm life cycle?
- Eggs or gravid proglottids are passed into external environment.
- Cattle and pigs become infected by ingesting vegetation contaminated by eggs or gravid proglottids
THIS IS WHERE VACCINE STOPS BEFORE INVADES MUSCLE. - Oncospheres hatch, penetrate intestinal wall, and circulate to musculature.
- Oncospheres develop into cysticerci in muscle.
- Humans infected by eating the raw or uncooked infected meat.
- The scolex attaches to intestine
- Adults in human’s small intestine
How were vaccines developed for T. ovis in Australia?
Can’t get enough oncospheres to vaccinate all the sheep with.
So generate recombinant antigens.
mRNA from oncosphere.
Express cDNA in E.coli. Screen for antigens with antibodies from immune sheep-> you pick the right antigens.
Then vaccinate-> Identified 3 major antigens.(45,16,18 kDa).
= The first ever recombinant parasite vaccine.
Because the recombinant parasite vaccine worked in T. ovis what happened then?
Looked for homologues of these antigens in T. saginata and T.solium.
And also homologues found in E. granulosis.
Have been found and are in vaccine trials now.
How do we know that vaccines for malaria are a good idea/potentially achievable?
- Protective immunity can be achieved in all animal models tested.
- Age-dependent immunity in humans in endemic areas.
- Immunoglobulin from immune donors can transfer protection to non-immune people.
- Vaccination with irradiated sporozoites (the stage which the mosquito squirts into you) confers sterile protective immunity in humans.
What are the Merozoite antigens that people are interested in to develop vaccines against malaria?
Based on two main antigens:
Merozoite surface protein 1 (MSP-1)
Apical membrane antigen 1 (AMA-1)
Both identified in all species and homologues in rodent and simian species.
What is the RTS,S/AS02 vaccine?
for malaria
RTS=Single polypeptide corresponding to amino acids of circumsporozoite protein fused to the amino terminus of hepatitis B surface antigen. Recombinant protein. Gave good immune responses.
AS02= oil in water adjuvant.
The vaccine induces high levels of Circumsporoite repeat specific antibody and IFN-gamma production.(i.e. a Th response).
Recipients were 30%-60% less likely to have bad symptoms. Don’t stop infection but stop getting sick.
Works short term so isn’t going to be the chosen one.
What is sanaria?
Massive production of irradiated P.falciparum sporozoites for use as a vaccine.
Have to give loads of sporozoites so a big job.
