Production and Synthesis
What does the mRNA in the vaccine in the vaccine code for?
A. Antigens
B. Antibodies
Answer: A. Antigens
Antigens are foreign particles that your body reacts to. In this case, the mRNA vaccines code for the spike proteins of the SARS-CoV-2 virus, which is a foreign particle.
Which part of the virus is the SARS-COV2 vaccine actually "attacking"?
Hint: Guess what the word Corona refers to...
Answer: The spike proteins; the spike proteins in the virus look like the solar corona.
What is the main purpose of the spike protein in the COVID-19 coronavirus?
A. Evading host immune system
B. Entering host cells
C. Mimicking harmless particles
D. Binding to host ribosomes
Answer: B. Entering host cells
The SARS-CoV-2 viral spike is a glycoprotein (S): (glycoprotein = polysaccharides + protein). It is crucial for mediating virus entry into cells.
Its protein structure is made of different domains like the Lacl repressor
S1 Domain
N-terminal domain
C-terminal domain
Receptor-binding domain (RBD)
Mediates binding to entry receptor angiotensin-converting enzyme 2 (ACE2) proteins on cell surface
S2 Domain
Controls machinery for fusing host and viral membrane to allow the contents inside the virus membrane to enter the host cell
Which company's mRNA vaccine was the first mRNA product to achieve full FDA approval in the U.S?
A. Pfizer-BioNTech B. Moderna
Answer: A.
Are mRNA vaccines safe?
A. Yes
B. No
Answer: A. Yes
mRNA vaccines are safe. There are some mild reactions to vaccination which occur in almost everyone (pain at sight of injection, fatigue) and some more serious effects can occur, but these are rare. The immunity from Covid-19 far outweighs the risk of getting an mRNA vaccine.
What components of transcription must be added to man-made mRNA to increase the efficiency of translation in human cells?
A. 5' cap only
B. 3' poly tail only
C. 2’-O-methylation
D. A&B
Answer: D.
Prokaryotic cells do not need to undergo post-transcriptional mRNA processing. Eukaryotes require 5' caps to bind to ribosomes. Prokaryotes, however, find ribosomes through signalling.
What are the structural elements of mRNA?
Answer:
a 5′ cap,
a 3' poly(A) tail,
a protein-coding sequence,
and 5'/3' untranslated regions (UTRs)
This part of the virus fuses the virus membrane with the host cell membrane…
A. S1 domain
B. N-terminal domain
C. Receptor-binding domain
D. S2 domain
Answer: C. Receptor-binding domain
The SARS-CoV-2 viral spike is a glycoprotein (S): (glycoprotein = polysaccharides + protein). It is crucial for mediating virus entry into cells.
Its protein structure is made of different domains like the Lacl repressor
S1 Domain
N-terminal domain
C-terminal domain
Receptor-binding domain (RBD)
Mediates binding to entry receptor angiotensin-converting enzyme 2 (ACE2) proteins on cell surface
S2 Domain
Controls machinery for fusing host and viral membrane to allow the contents inside the virus membrane to enter the host cell
Check whether the following statement is true:
Coronavirus outbreak induced the invention of the first batch of mRNA vaccines on humans.
A. True B. False
Answer: B.
False, the first batch of mRNA vaccines was applied to deal with the Ebola virus epidemic in Africa.
What are some common AEFIs (adverse events following immunization) of mRNA vaccines?
A. Death by brain hemorrhage
B. Fatigue, myalgia, fever, and headache
C. Degradation of cartilage in the knees and elbows
D. Uncontrollable sneezing
Answer: B. Fatigue, myalgia, fever, and headache
The most reported AEFIs from mRNA vaccines are headache, fever, fatigue, and nausea. These effects are not chronic and do not last for more than a few days on average. Out of 18,755 people who reported AEFI’s, 4974 reported Headache (27%), 3577 reported fever (19%), 3123 reported fatigue (17%), and 2515 reported nausea (13%).
Similar to mRNA processing, what is the importance of 5' capping in the transcription of mRNA for the COVID vaccine?
Answer:
5' capping
- Provides stability for the mRNA
- Becomes ribosome binding site/ initiation area for translation (AUG)
How are mRNA vaccines different compared to other vaccines, in other words, what exactly is being delivered by the vaccine and why?
A. Other vaccines use the live virus, which is then injected into the body, and the memory cells act on it, while mRNA vaccines use the template for the antigen.
B. mRNA vaccines use the attenuated form of the virus, which is injected into the body and the immune system responds to the foreign object, while other vaccines use the live virus.
C. Other vaccines inject the attenuated form of the virus into the body, while mRNA vaccines provide the body with the template for the antigen.
D. mRNA vaccines use the DNA of the virus, while other vaccines use the RNA form of the virus.
Answer: C. Traditional vaccines inject an attenuated and mostly harmless form of the virus into the body as antigens, such as viruses that have been sterilized, while mRNA vaccines provide the body with the template for the antigen for it to produce.
What is the best reason that COVID-19 might attack the lungs?
A. Relative lack of immunoglobulin G in alveolar cells
B. Alveolar cells have ideal moisture conditions for virus replication
C. It is easy for the virus to get to the lungs through the respiratory system
D. ACE2 proteins expressed on the alveolar cell membrane
Answer: D. ACE2 proteins expressed on the alveolar cell membrane
The ACE2 gene is the gene that codes for the ACE2 protein in human
The ACE2 protein is functional receptor for both SARS-CoV and SARS-CoV-2, which means that the spike proteins bind to ACE2 to enter cells.
Negative regulator (NOT gene regulation) of the renin-angiotensin system, which controls blood pressure, fluid and electrolyte, and vascular (blood vessel) systems.
Expressed on the surface of lung alveolar cells (little bubbles inside lung) and surface of small intestine enterocytes
Possibly why the COVID-19 attacks the lung alveoli so aggressively!
Check whether the following statement is true.
mRNA was first discovered in the last 40 years.
A. True B. False
Answer: B.
False, it was first discovered in the early 1960s
What is the most dangerous AEFI of mRNA vaccines?
A. Death
B. Hypertensive crisis
C. Supraventricular tachycardia
D. Rapid onset Stage 4 Leukemia
Answer: A. Death
Death is the most dangerous AEFI from mRNA vaccines. It is often caused by an escalation of a more serious side-effect, such as hypertensive crisis, supraventricular tachycardia, or anaphylaxis. However, death is very rare, with a rate of under 0.55%.
Nucleoside is a subunit of a nucleotide but without the phosphate group. How does modifying the nucleoside help with the vaccine? Hint: it is similar to 5’capping.
Answer: It helps to improve the stability of the mRNA in a vaccine technology known as modRNA, which is used by both the Pfizer and Moderna vaccines.
Why are mRNA vaccines delivered by lipid nanoparticles?
A. To prevent nuclease degradation of mRNA.
B. Because RNA can easily bind with other RNA molecules
C. Lipids are good for the body
D. To prevent degradation of the vector DNA.
Answer: A. To prevent nuclease degradation of mRNA.
The lipid nanoparticle helps protect the mRNA that the nanoparticle holds from RNases (degradation of RNA by RNA digesting enzymes).
How do antibodies defend against the virus?
A. Identifies the virus and envelops it
B. Identifies the host cell and stops it from making more viruses
C. Identifies the virus and binds to its spike protein
D. Identifies the virus and releases cytokines to kill it
Answer: C.
Since the spike protein is on the surface of the virus, it is the key target for most neutralizing antibodies i.e. antibodies that neutralize the virus, making it inert.
S230 anti-SARS-CoV is one such antibody, which mimics a receptor (mimics ACE2) to trick the virus into binding with it and prematurely starting the virus fusing process, rendering it non-potent.
Other antibodies include immunoglobulin G (IgG) , IgM, and IgA
Also involved are CD4+ T cells that are specific to the spike protein:
When was mRNA first applied in the medical field？
A. 1969
B. 1974
C. 1984
D. 1976
Answer: C. 1984
Using an RNA-synthesis enzyme from a virus, well-formed and biologically active mRNA was produced in the lab by a team led by biologists Douglas Melton, Tom Maniatis, and Michael Green at Harvard University.
How does the safety of mRNA vaccines compare to influenza vaccines?
A. they have exactly the same safety data
B. mRNA vaccines can cause more heart related adverse effects, whereas influenza vaccines can cause more neurological effects
C. mRNA vaccines are much more unsafe than influenza vaccines
D. influenza vaccines are much more unsafe than mRNA vaccines
Answer: B. mRNA vaccines can cause more heart related adverse effects, whereas influenza vaccines can cause more neurological effects
Side effects like hypertensive crisis and supraventricular tachycardia are more common in mRNA vaccines whereas side effects like seizures and myelitis are more common when vaccinated with influenza vaccines. It is unknown why this happens; more research must be done to find out.
Why is purification during IVT (in vitro transcription; mRNA production) important?
A. So that the antigens can be coded properly
B. Contaminants can induce innate immune response
C. It is easier for the cell to recognize the mRNA
Answer: B. Contaminants can induce innate immune response
After the IVT contaminants and residues will be left over which is harmful as can lead to extreme immune response. Purification minimizes such residues to avoid complications.
What are the different components of the lipid nanoparticle?
A. Lipids, gold nanoparticles, mRNA.
B. Helper Lipid, PEG-2000 lipid
C. mRNA, cholesterol, helper lipid, PEG-lipids, ionizable lipids.
D. mRNA, cholesterol, helper lipid, PEG-lipids, cationic lipids.
Answer: C. mRNA, cholesterol, helper lipid, PEG-lipids, ionizable lipids.
Ionizable lipids: They are ionizable lipids, i.e. at an acidic pH they are positively charged, while at a physiological pH they are neutral, and hence aren’t toxic. They directly bind to the mRNA. The ionizability of the lipid at a low pH allows for endosomal escape, and hence the delivery of the mRNA.
Cholesterol helps maintain the strength and structural integrity of the lipid nanoparticle.
PEG (polyethylene glycol) lipids: They help in further providing stability to the nanoparticle. The amount of PEG lipid affects particle size. PEG lipids are also useful for targeted delivery, they do so by conjugating specific ligands to the particle.
Helper lipids: They provide the structure to the lipid nanoparticle along with Cholesterol and PEG lipids.
How is protection against future infections achieved?
A. Neutralizing antibodies are expressed more frequently after infection
B. T-cells are primed against cells that seem infected
C. Memory B cells are accumulated in the liver
D. Angiotensin synthesis is up-regulated
Answer: A. Neutralizing antibodies are expressed more frequently after infection
Researchers are not sure how the human body defends itself against SARS-CoV-2 reinfection but think it is related to neutralizing antibodies (nAbs). This is supported by observations of mice and other animals, which show high levels of nAbs immediately after infection, and maintain a high level for an extended period of time afterwards.
Memory b cells are increased and produce said antibodies
Both Phizer and Moderna elicit nAbs expression by injecting the cell with a mRNA transcript of human-modified S for stability for the cell to translate, which once antibodies start recognizing the virus, triggers an immune response.
What was the biggest technical challenge the scientists had to overcome when developing mRNA vaccine technology? (Hint: related to information flow in cells)
The biggest challenge for scientists was trying to preserve mRNA in vivo (i.e. after injection) for long enough to be delivered to the target cells and translated into proteins. mRNA survives for short periods inside cells because of the prevalence of RNases inside and outside cells.
Are mRNA vaccines safe for the Immunocompromised/elderly?
A. Yes
B. No
Answer: A. Yes
Immunocompromised people are at a much greater risk of becoming seriously ill after contracting COVID-19, therefore they are the highest priority group to receive immunization. However, there is data suggesting that patients who have gone through organ transplants have trouble developing antibodies following immunization. This is because immunosuppressants are given to patients after organ transplants, and they interfere with the body’s immune response to vaccination. Despite this, vaccination is recommended for immunocompromised patients.
Elderly patients are at more of a risk for serious side effects following vaccination, however the risks of contracting COVID-19 outweighs the risk of vaccination, and it is recommended that elderly populations should get vaccinated.