Malaria Vaccine and Immunity Flashcards
Describe at least three ways in which the malaria parasite evades the immune response.
Allelic polymorphism
Expression of novel antigens at each stage
Antigenic variation
“Hide and seek” nature of infection, moving in and out of different host cells
List the challenges to malaria vaccine success.
Cool chain (a temperature-controlled supply chain) Infrastructure Politics Population movements Poverty Parasite evolution Eliciting a PROTECTIVE immune response
Evaluate the success of vaccines targeted at the sporozoite stage of the life cycle
Use shite written on pages
Discuss other potential vaccine candidates
Vaccines targeting:
Liver stage antigens
Blood stage antigens e.g. merozoite antigens
Mosquito stage antigens
Transmission blocking vaccine could help prevent the spread of evasive strains
Explain what a “cocktail” vaccine is, and why it is advocated as the future of malaria control.
Long-term vaccine effectiveness will probably only be achieved with combination, multi-component vaccines
This is a similar strategy to producing combination drug regimes i.e. make sure that if the parasite can escape one block, it then encounters another
What are GAPs?
Genetically attenuated parasites.
Irradiation messes up DNA but there is no way of knowing what DNA it messes up, and whether all sporozoites have been irrevocably damaged
Researchers have found 2 genes that are essential for parasite development inside hepatocytes
Using transfected cell lines of P. falciparum, they have produced GAPs that have one or the other of these genes inactivated and also a GAP cell line that has both genes inactivated
What is the most successful malarial vaccine to date?
RTS,S, elicits ~50% protection
R = GM yeast to produce CS protein’s repeat region
T = shows that it is a T cell antigen that helps the immune system to recognise the malaria parasite
S = hepatitis B antigen which is fused to yield a high immune response
Final S = represents the unfused hepatitis B antigen that is induced to make the entire antigen on the parasite’s surface large enough to be noticed by the immune system
What are the properties of the CS?
Circumsporozoite protein forms a dense coat on the parasite surface which it sheds in the host, trails can be seen behind motile parasites
Possess tandem repeats and is highly immunogenic
In P. falciparum, NANP and NVDP repeats have been identified
Antibodies in a vaccine to the sporozoite stage might stop them getting into hepatocytes and gave also been shown to elicit immunity against the liver stage
Explain vaccines targeting liver stage
After analysis of people’s naturally acquired immune responses, some promising candidate vaccine molecules have been selected from the liver stage of the lifecycle
Some of them are are poorly immunogenic because they have a limited number of T cell epitopes; hence they are MHC restricted and induce an appropriate immune response in only subsets of the population => need for an adjuvant
Explain vaccines targeting blood stage
The asexual blood stage merozoites also have different immunogenic antigens
Examples of candidate antigens: merozoite surface proteins MSP-1 and MSP-2
They also have tandem repeats of amino acids
Antibodies can prevent invasion of fresh erythrocyte
What are transmission blocking vaccines?
It was known over 20 years ago that immune responses to gametes or the ookinete (zygote) stage of malaria could modulate transmission via mosquitoes
e.g. Pfs25, Pvs25 expressed on mosquito stages of parasite life cycle (zygotes and ookinetes)
Antibodies and immune cells ingested by the feeding mosquito can be active in the mosquito midgut (as the parasite undergoes its sexual stage of the cycle) and prevent further development of the parasite
Explain DNA vaccines
DNA vaccines favour a cell-mediated immune response
DNA plasmid vector vaccines carry the genetic information encoding an antigen, allowing the antigen to be produced inside of a host cell, leading to a cell-mediated immune response via MHC I pathway
The plasmid DNA vaccine carries the genetic code for a piece of pathogen or tumour antigen
1.DNA transcribed in the nucleus
2. mRNA translated into protein
3. then degraded by proteosomes into intracellular
peptides
4. binds MHC I molecules
5. Presented on cell surface
6. binds cytotoxic CD8+ lymphocytes, inducing a cell-mediated immune response to antigen encoded in DNA vaccine
Because DNA vaccines generate cell-mediated immunity, the hope is that they will be effective against some difficult pathogens even though standard vaccines have failed to work
