L12 - HPV (4) Flashcards
What HPV is common in co-infection?
HPV45
Which HPV vaccine gives better cross-protection
Cervarix
What are the 3 new approaches to HPV vaccines?
Include L1 from other HPVs
Include L2
Epitope swapping
How can including L2 improve HPV vaccines?
more conserved between diff. HPV types
BUT - only exposed when virus is getting into cells
How can epitope swapping improve HPV vaccines?
Make a chimera combining different HPV types
Other alternative to IMPROVING the HPV vaccine?
cheaper and more accessible
HPV vaccine made in E.coli?
problem with LPS
still quite expensive with cell free expression
CECOLIN
How can HPV subunit vaccines be good?
12-pentamer icosahedral particles
BUT STRUCTURE OF HPV DOES NOT OBEY RULES OF QUASI EQUIVALENCE
How can uptake of vaccines be improved?
Microneedle patches instead of bigger single needles
4 ways to improve vaccines?
1) vaccine made in E.coli
2) subunit vaccine - isolated pentamers
3) Deliver alongside current vaccines
4) Change delivery strategy for better compliance e.g. micro-needle, single dose
What is the aim of a therapeutic vaccine
trigger immune response in individual already infected
Use VLP that is easy to make foreign epitopes e.g. HepB core
How can removing oncoproteins be a different approach in vaccines?
oncoproteins can interact with cellular protein
inhibit or remove oncoproteins to reomove interacts
What technology can make RNA aptamers?
Selex
What are RNA aptamers?
oligonucleotides that fold into complex structures - bind to targets in conformation-dependent manner
How are RNA aptamers stabilised against nuclease attack?
2’fluoro pyrimidines
What is SELEX?
successive rounds of +ve and -ve selection with target of interest
library of RNA molecules
What are the effects of E7 aptamers in cells?
Bind to E7 with HIGH SPECIFICITY AND AFFINITY
cause apoptosis of HPV-infected cells
Do aptamers induce apoptosis?
YES - amount of apoptotic cells increases with number of aptamers
What other viral proteins may be used for targets in antiviral therapy?
E1 helicase inhibitors?
inhibit interactions between E2 and host proteins?
How do you identify a virus as the causative agent of a tumour?
DTS - Digital Transcriptome Subtraction
cDNA from RNA from tumour sample
sequence cDNA - high throughput
generates transcriptome database of tumour
subtract all known human sequences
remaining - pathogen cDNAs
Cons of DTS?
Does not show cause and effect of virus
Is Merkel’s cell polyomavirus a Papilloma?
NO - polyomavirus is more complex
What are Merkel cells?
touch receptors in skin - connect to nerves
What is Merkel cell carcinoma?
neuroendocrine carcinoma of skin
develops on sun-exposed skin
flesh-coloured/red/blue bump
What is TS-assoicated polyomavirus? (Trichodysplasia Spinulosa)
growths on face
not yet attributed as causative agent