Flashcards in Papillomaviruses (HPV)- vaccination and treatment Deck (28):
More conventional vaccines such as Poliovirus vaccines have proved very effective (cases reduced by 99% and only two countries still have cases-Afghanistan and Pakistan). What are the two vaccines given for such a virus?
OPV- mutant virus
IPV- inactivated virus (chemicals kill the active virus for this vaccine)
Both produced from live virus. Hela cells are grown in large vats and these are full of virus particles.
HPV does not grow in cell culture/ liquid culture like the poliovirus due to its lifecycle being mirrored to the cycle of epithelium cells. Rafts are used in labs but the yield is very small so is not used for vaccines. So how is this overcome?
Only parts/subunits of the virus is used; often using a protein from the capsid (L1). So all vaccines are made from virus-like particles of L1. These are all non-infectious due to absence of viral genome
Which two vaccines are in commercial use at the moment?
Gardasil- tetravalent- targets HPV 16/18/6/11
Cervarix- bivalent- targets HPV 16/18
What shape are viral capsids?
Icosahedra (20 sided shape)- only one copy of each protein so is economic for the virus (no need to produce many elements)
How can a virus build a larger capsid compared to that of a icosahedra?
Each protein can code for many copies/many triangles instead of just one so to make the capsid larger
As the capsid gets larger, what happens to the symmetry of the capsid?
Not all proteins are in equivalent position so perfect symmetry is broken. Proteins will cluster into fives or sixes (pentamers and hexamers)
HPV breaks the capsid symmetrical/pattern rule, how?
It has no hexamers at all. It produces a T=7 capsid with only pentamers
BPV structure is used to study the structure due to ease of getting it as it grows on cow skin. Why is it not possible to get a crystal structure of HPV?
Is not possible to get enough to form a high resolution whole structure but BPV supports that this virus uses only pentamers and no hexamers
Which virus is similar in capsid structure to HPV?
SV40 (was once classified under papillomavirus family) due to its pentameric pattern
What is meant by the pentamers making hexameric interactions?
Pentamers make interactions with six other pentamers in the capsid structure- this makes it a stable network
L1 alone can be heterogeneous (sizes and shapes are different). What can be done to make them more homogeneous?
Disassemble and re-assemble these virus-like particles to get rid of any extraneous nucleic acid. This is actually part of one of the vaccine purification processes
Why is it important for a vaccine capsid to have a homogeneous structure?
The immune system prefers a regular pattern so it will induce a better immune response, In addition, less material is lost so the product will be cheaper and it is easier to get through regulations which question the purity of the material
Are there more human or animal papillomaviruses?
More human ones known but most likely there are more animal ones
What are the structural differences between low-risk and high-risk HPVs? How does this affect protection against different types of HPV?
E6 and E7 sequence and affinity for binding partners (pRB, p53 etc)
L1 sequences are variable so it is also hard to tell if there will be any cross over of vaccination/protection against other types of HPV than the one you've been vaccinated for
How was the Cervarix vaccine made?
Made from truncated L1 proteins in insect cells with recombinant baculovirus. Truncated L1 use meant that they did not have to undergo many purification processes that Gardasil did. A proprietary adjuvant ASO4, alum + TLR4 ligand, MPL was used to boost the innate immune response (adjuvants are tightly regulated but the most common one is alum)
How was the Gardasil vaccine made?
Through particles being dis-assembled and reassembled again and using yeast and Alum-based adjuvants
HPV vaccines are very expensive, which foundation helps subsidise them in some countries?
The Gates Foundation ($5/dose) to encourage vaccination. The price most countries can afford is $1/dose but this is a high ask as it has to include needle, safe storage, the actual vaccine etc.
Who was Ian Frazer?
He worked on the development of VLPs and then on the idea of vaccine
In the 1990s, what was the vaccine tested on? What was tested in the 2000s?
Cottontail rabbits in the 1990s, then young women that were HPV 16/18 negative who were then monitored for two years
Why were HPV 6 and 11 in Gardasil useful?
Both these are low-risk genital wart producing HPVs but they have a large economic burden and may last a life time so finding a way of preventing it is beneficial. Also a shorter monitoring time is needed to see a decrease compared to cervical cancer
What is the current vaccination programs that girls undergo for Cervarix?
Used to be 3 injections over 6-12 months but now it has gone down to 2 and switched to Gardasil as the results of this were very good and had added benefits of protection against HPV 6 and 11
Why do we only vaccinate girls in this country?
Purely financial reasons- it is actually more effective to vaccinate men. Some countries are changing and are now vaccinating boys and now offered to gay men in the UK
Is it possible to eradicate HPV?
There are many different types so it is very difficult and also benefits of vaccination is not seen for a long time
What sort of HPV screening test is being used?
PCR-based screening tests are being used and there has been 60% drop in cases of CIN 2/3 in uk over the last 30 years due to this
Cervical cancer is the number 2 cancer killer of women under 35 world wide. It is much harder in countries outside the west to get screening tests for it. Describe a way that's being used to screen for HPV in these countries.
Putting vinegar on the cervix and looking for colour change which indicates lesions and therefore that treatment is needed
Why are head and neck cancers hard to diagnose?
Due to the difficulty of performing biopsies on the oropharynx and nasopharynx
CIN2/3 and cervical cancer often involves surgery. What is conisation?
Excision of a cone-shaped or cylindrical wedge from the cervix including the transformation zone and part of the endocervical canal
A relatively high risk of recurrence.
Scarring may result in functional problems (e.g. in pregnancy)