Vaccines Flashcards
What happens post vaccine?
Recombinant DNA transcribed into mRNA
Loaded into vector
Injected
Enters cells via endocytosis
TLR triggers IFN–1 pathway- pro inflammatory
mRNA binds to ribosomes translated into antigen
Antigen is either secreted or membrane bound
What is immune sensing of uridines?
Inateimmune system looks for exogenous RNA to destroy via inflammation
It does this because the TLR7 receptor reacts with uridine in delivered mRNA
Substitute uridine with m1mu
TLR7 cannot recognise delivered mRNA
What is the inate immune response?
Location (immediate)
Macrophages recognise pathogen activating the system
Dendrite cells pick up pathogens antigens and takes to the T and B cells to activate
Thus activating compliment system
What is the adaptive immune response?
Humoral-production of antibodies from B cell
Cell mediated- T cells and macrophages
Takes longer, especially if first time infection
What delivery vectors are used for vaccines?
Lipid nano particles (LNPs)
Cationic unionised (but ionisable) lipids
Anionic DNA
Form lipoplex
What are the characteristics of LNP’s?
Lipid bilayer
Cholesterol – for structural stability
Helper phospholipids – support lipid bilayer
PEG lipids- shield surface charge
How do LNPs work?
Cationic ionisable lipids form lipoplex
Undergo endocytosis
Lipids are ionised
Become fusogenic with endosomal membrane
Cytosolic delivery of mRNA
What is the structure of conventional mRNA?
5’ and 3’ UTRs
Target antigen coding sequence
(No amplifying proteins)
What is the structure of self amplifying mRNA?
5’ and 3’ CSE sequences
nsP1-4 genes
Target antigen sequence
nsP1-4 forms RdRP complex
RdRP complex recognises CSE sequences
Amplification
What is trans amplifying mRNA?
Two separate transcripts
Conventional with nsP1-4 genes but no coding sequence
One with CSE sequences and antigen coding sequence
Conventional forms, RdRP complex which can read CSE sequences on other strand, amplifying antigen
What best route of delivery for vaccines
Intramuscular
How can vaccines be given intravenously?
When used with cationic LNP vector
What type of vaccine was the SAR-COV-2 vaccine?
Nucleoside modified mRNA
What is a bivalent vaccine?
Contains two strains of disease
The original strain and most recent variant
