Flashcards in Papillomaviruses (HPV)- the future of vaccines Deck (17):
Why might there been a need for therapeutic methods on top of vaccines?
It takes a while for the results of the vaccines to be seen and also not all HPVs are included in the vaccine
What is the % coverage needed for herd immunity to be effective? Why may it be difficult for developing countries to achieve this?
85. Several doses are needed and logistically it may not be possible for people in developing countries to have access to all of them
Which country is very good at surveillance of HPV and showed 10% more vaccine uptake than england in 12-13 yr olds?
What are two ways of including more HPVs in your vaccine for increased cross protection?
Include L1 from other HPVs (is being done) or include L2 proteins as this is much more highly conserved across HPV types
Pseudoviruses are cultures which contain L1 and L2. What is evident from imaging these compared to L1 alone? Why may it be beneficial to include L2?
Much more regular/ consistent looking. Due to conformational change during entry of virus, L2 is exposed so the immune system would be able to react against it just like L1
There are many other ideas for making vaccines. One is to use E. coli. Why is this difficult?
E.coli cell walls have many lipid polysaccharides which are immune agonists. These are unwanted in vaccines. There are some new E. coli being made with a reduced level of lipid polysaccharides
What is the difference between the normal vaccines and therapeutic vaccines?
Normal ones prevent illness whereas therapeutic vaccines is just to boost your immune system in order to help you clear the infection
Describe the way a therapeutic vaccine can work?
By producing a scaffold presenting HPV antigens e.g Hepatitis B scaffold/ core particle decorated with HPV L1 sequences
How can therapeutic vaccines affect the viral genes? What is the problem with it?
It could be possible to target dsRNA (RNA silencing) to down-regulate gene expression (translational repression). It is difficult to get RNA though and it is also hard to be certain that it is specific to the gene of interest (off-target effects) but would be effective if the delivery system was more accurate
What are aptamers and what are their advantages as an alternative?
Aptamers are oligonucleotides that fold into complex
structures and bind to their targets in a conformation-dependent manner (instead of knocking down a protein, it just stops it functioning)
• bind with a high specificity and affinity
• can be denatured and re-folded
• can modulate protein-protein interactions
How are aptamers made by Selex?
Process of certain RNAs in a huge library binding to the target and then amplifying those which do. They then go through the binding process again and those which do not bind are removed. You end up with a pool of proteins which bind to your gene of interest
What can some aptamers induce in cells?
Induce apoptosis therefore killing the cell with the virus
What did experiments show aptamers target and how was this shown?
The experiments suggested that aptamers signalled E7 for degradation and this was shown by decreased E7 levels and increased RB levels (the proteins that E7 ubiquitinise)
What is being worked on in reference to aptamers being used more?
The delivery process/ entry to cells
What are the problems with using other viral protein targets such as E1 helicase or the interaction between E2 and the host?
They are very variable between HPV types
How do you identify whether a virus is a causative agent of a tumour?
Digital Transcriptome Subtraction (DTS)- get mRNA from the tumour cells which then tells you about what genes are being expressed. You can then create cDNA and subtract all the known human DNA which leaves you with the viral genes