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different types of vaccines - Coggle Diagram
different types of vaccines
mRNA
low risk of insertional mutagenesis
does not integrate into host gneome
no risk of carcinogenesis/IM
high potency
accelerated development cyces
low cost manufacture
does not require cell cultures or toxic chemicals - no chemical or biological contaminations in the final products
can be easily scaled up to commercial levels
delivery
mRNA encoding the immunogens is encapsulated in a lipid shell
upon delivery into cytoplasm, host cell machinery directs the translation of the antigen proteins that induce effective and long-lasting immune responses
forms of mRNA vaccines
non amplifying mRNA vaccines
fundamental structure
non-amplifying mRNA
5' cap
essential invariant for efficient protein production by stabilising mRNA molecule
addition can be achieved either
via a post transcriptional enzymatic reaction guided by the vaccinia virus-capping enzyme
via a co-transcriptional reaction by incorporation of the synthetic cap or anti-reverse analogues
additional post-translational modifications such as 2'-O-methylation to introduce a cap 1 structure into an in vitro transcribed mRNA further improve the translational efficiency and precent undesirable immune responses
5' untranslated region (UTR)
gene of interest encoding region
modifications can increase protein production
chemical alterations of mRNA molecules
M1-methylpseudodouridine
pseudouridine
replacement of uridine with pseudouridine confers protection from degradation mediated by RNase L
other nucleoside analogues
substitution of rare codons with synonymous codons
enrichment of GC content in the mRNA molecules
3' UTR
flank coding sequence - important regulatory role in stability and translation
wide range originating from viral or eukaryotic genes have been deployed to promote mRNA in cell stability and translation efficiency
composition and structure are key determinants of the intracellular stability
UTRs from human haemoglobin subunit beta (hHBB) shown to confer higher stability and higher potential for protein production
UTR combination for high protein expression is cell type and species dependent
optimal UTRs need to be selected from naturally occurring UTRs
Poly(A) tails
important impact on protein translation by protecting the transcriptional body from exonucleolytic degradation
length is associated with translation efficiency in a cell type dependent manner
most therapeutic mRNAs bear a polyA tail with a length of approximately 50-100nts
can be incorporated into transcript
by polyA polymerase mediated tailing
by direct synthesis using a plasmid template harbouring polyT sequences during in vitro transcription reaction
Viral Vector
current types of vaccines used in the veterinary field
inactivated vaccines
poor immunogenicity
live attenuated vaccines
reversion to viulence is an issue
recombinant subunit vaccines
limited protective immunity against a heterogeneous virus