Lecture 7 Vaccines

Question 1

Describe the components critical for stability in the cytosol of mRNA vaccines.

Answer 1

5’ CAP,
3’ Poly A Tail,
5′ and 3′ UTRs around the ORF,
poly-A tail length,
G-C content,
codon optimization.

Question 2

What are the mechanisms involved in mRNA vaccine activation?

Answer 2

Activation of CD8+ T Cells,
CD4+ T-Cells,
B-Cells,
IFN-1 Pathway,
antigen presentation by MHC Class I & II,
induction of both cellular and humoral immunity.

Question 3

How does the immune system sense uridines in mRNA vaccines?

Answer 3

Activation of the innate immune system,
leading to inflammation,
translation inhibition,
mRNA degradation; replacement of uridine with m1Ψ can prevent immune activation.

Question 4

Define the types of alternative mRNAs used in vaccines.

Answer 4

Conventional mRNA (non-replicating), self-amplifying RNA, and trans-amplifying RNA.

Question 5

What are some delivery vectors used for mRNA vaccines?

Answer 5

Naked mRNA, electroporation, protamine, cationic nanoemulsion, modified dendrimer nanoparticle, protamine liposome, cationic polymer, polysaccharide particle, cationic lipid nanoparticle, and LNPs.

Question 6

Describe the components of LNPs used in mRNA vaccine delivery.

Answer 6

Cationic ionizable lipids for mRNA complexing, PEG lipids for charge shielding, helper phospholipids for bilayer structure support, and cholesterol for structural stability.

Question 7

How does the presence of cationic ionizable lipids in LNPs contribute to mRNA vaccine delivery?

Answer 7

They are required to form complexes with mRNA, facilitating its delivery into cells.

Question 8

What role does cholesterol play in LNPs for mRNA vaccine delivery?

Answer 8

Cholesterol provides structural stability to the lipid nanoparticles, aiding in the efficient delivery of mRNA into cells.

Question 9

Describe the role of cationic ionisable lipids in lipid nanoparticles (LNPs)

Answer 9

Cationic ionisable lipids are un-ionised within LNPs, forming electrostatically stable lipoplexes. After endocytosis, they become ionised and interact with endosomal membranes for cytosolic delivery of therapeutic mRNA.

Question 10

Define the process of endocytosis in the context of lipid nanoparticles

Answer 10

Endocytosis is the cellular process by which cells internalize substances from the external environment by engulfing them in a vesicle formed from the cell membrane.

Question 11

How do cationic lipids within LNPs facilitate cytosolic delivery of intact therapeutic mRNA?

Answer 11

After endocytosis, cationic lipids become ionised and interact with endosomal membranes, enabling fusion and release of therapeutic mRNA into the cytosol for effective delivery.