Innovation in vaccines
14 important questions on Innovation in vaccines
What was with SARS CoV-2 the first step for vaccin development?
What is the standard vaccine development? And why could the process be faster for covid?
- Existing infrastructure for novel vaccin platforms such as mRNA an DNA (virus vector) based vaccines -> they could go immediate to phase I
- Phase I,II and III were conducted in an overlapping timeframe.
- Availible knowlegde for example on cancer.
What was the problem with the vaccin development for covid?
You need a lot of educated and lab trained professionals.
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What were the two first vaccins against covid?
- CanSino product, chinese military
- Gamaleya Research Institute in Russia but without phase 3 trials
Which three vaccins were the front runners in Europe?
They were approved for emergency use. Because they dit not encounter safety concerns.
How does a mRNA vaccine work?
- Negative charged mRNA molecule needs to go across the hydrophobic lipid bilayer membranes => surrounded by ionizable lipid (PEGylated lipid) = low in inflammatory potential
- Endocytoses to come into the cell
- RNA in cytoplasma (it need to be stable there, so it is modificated to be stable)
- Recognitions by ribosomes
- Spike protein is made and seeks receptor on cells = ACE2 receptor
- Arm => muscle cells. Dendritic will drawn to the side of the infection.
- Bring RNA to lymphatic tissue.
- Specific immune reaction.
The proteasomes => degradate the protein => MHC I presentation. => immune respons. (B-cells and T-cells)
Which reaction do the current vaccins call the most for?
What is the history of the mRNA vaccins?
How are the covid vaccins made?
- You need know the sequence for the coding information you want to be translated.
- You have to construct a DNA template that has to be copied. = 5-cap, 5 UTR, ORF, 3UTR, poly-A-tail.
The mRNA is then made in an in vitro transcription. The ribosomes, the metylated cap unit etc is in one glass. You heat it to a correct temprature.
- Purifying the mRNA form the production vat. You want to have it as pure as possible
- Mixing with the lipids.
What are the four structural proteins of covid virion?
- Membrane protein
- Envelop protein
- Spike protein
- Nucleocapsid protein (protect, help deliver the virus genome)
What are the accessory protein of SARS CoV-2?
ORF7a
Expressed in infected cell membranes.
What is important in the vaccin in the formation of the spike protein?
Nog nakijken.
What are two phenomena's that make things worse with the vaccin? Which stages of the vaccin development are really important?
- Antibody dependent enhancement (ADE) of disease
- Vaccine-associated enhanced respiratory disease (VAERD)
Pre-clinical trials
Clinical trials
What kind of vaccine platform does astrozenica use for there vaccin?
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