Pfizer mRNA COVID Vaccine
Previously, I discussed the current research surrounding ivermectin and its potential as a treatment for COVID-19 positive patients. In brief, the quality of the available research is poor, with many studies having severe problems such as missing controls or ambiguous data. Despite these issues, there is enough evidence that ivermectin could aid in quicker recovery from symptoms in patients with mild-to-moderate cases of COVID that do not require ventilators and could warrant additional research.
It was clear based on the published works that ivermectin does not represent a 'miracle cure' for COVID and should only be taken if prescribed by a physician. Lacking a wonder drug like penicillin that can target COVID and help severely ill patients recover, the best protection against COVID is to avoid infection altogether. The best tool currently available to prevent infection is vaccination with one of the three approved COVID-19 vaccines.
This blog will discuss how the Pfizer COVID-19 vaccine works, the ingredients in the vaccination, and the common side effects.
What is mRNA?
To understand how an mRNA vaccine works, we first need to briefly touch on one of the central tenets of biology, the pathway from DNA to protein. DNA is essentially the blueprint that dictates what an organism is, how it appears, how it functions, and how it behaves. The ribosomes take the data embedded in these blueprints and convert them to proteins which are complex molecules that serve important functions with regards to structure, function, and regulation of the body.
Since DNA is critically important to cells, it remains in a protective envelope called the nucleus in most organisms and communicates with the ribosomes through an intermediary molecule called mRNA. Messenger RNA (mRNA) takes the information coded in the DNA and carries it to the ribosome to create new proteins. In addition to protecting the DNA, the use of messenger RNA allows cells to regulate what proteins are manufactured, as only small portions of the DNA is transcribed into mRNA at any given time.
A cell requires the presence of its DNA throughout its entire life, but can make nearly limitless mRNA molecules to build the required proteins. Unlike DNA which is a robust, double-stranded helix, mRNA is single-stranded and degrades rapidly after transcription. This rapid degradation is critical as it allows the cell to change what areas of the DNA are transcribed and which proteins are produced quickly. If mRNA was longer lived it would interfere with the optimal functioning of the cell.
How does an mRNA vaccine work?
To create an mRNA vaccine, scientists identify the RNA sequence of a viral component (in SARS-CoV-2, this is the 'spike protein') that can be injected into a host to trigger an immune response. After injection with the spike protein mRNA vaccine, the foreign mRNA enters into the host's cells and instructs the ribosomes to make the spike protein. Since the mRNA only contains the material to generate new spike protein and NOT the entire virus, the host CANNOT be infected with COVID-19. As the spike proteins are manufactured, they leave the cells and enter into the bloodstream.
Eventually, the body's immune system notices these foreign proteins and destroys them. Through the course of destroying the foreign proteins, the body creates new cells that 'remember' these intruders and vigilantly search for reinfection. If the spike protein is found again, perhaps through COVID exposure, the body can produce a much quicker immune response, potentially preventing infection.
The image above shows the spike protein structure for SARS-CoV-2. These are commonly seen as little red triangles on drawings of the SARS-CoV-2 virus and are embedded in the outer membrane of the coronavirus. To effectively create a vaccine that can generate a rapid response, a protein accessible from outside the virus is ideal.
What is in the Pfizer COVID vaccine?
Interestingly, the Pfizer COVID vaccine has fewer ingredients than may be expected. According to the CDC website, the Pfizer COVID vaccine has ten ingredients:
- SARS-CoV-2 spike protein mRNA
- Lipids
a. Cholesterol
b. 1,2-distearoyl-sn-glycero-3-phospohcholine
c. 2[(polyethylene glycol (PEG))-2000]-N,N-ditetradecylacetamide
d. ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) - Salts and Sugars
a. Sucrose
b. Sodium chloride
c. Potassium chloride
d. Monobasic potassium phosphate
e. Dibasic sodium phosphate dihydrate
The first ingredient we discussed above, the SARS-Cov-2 spike protein mRNA is the genetic material injected into the host to allow cells to manufacture the spike protein and generate an immune response.
Lipid is a fancy word for fat and these serve to create an envelope that will allow the mRNA to enter the cells. Each cell has a membrane of phospholipids (fats with phosphate groups) that prevent water and other molecules from entering the cell, maintaining an internal environment that is vastly different from the external environment. The lipids listed here, aside from cholesterol, were likely manufactured to allow for maximum efficiency in entering the cell without damaging the mRNA inside. A predicted model for the lipid nanoparticle and how it protects the mRNA is seen below.
The salts and sugars serve to protect the vaccine during freezing, shipping and storage by creating an environment that will prevent degradation of the mRNA. These are all readily available and commonly-used ingredients. For example: sucrose is table sugar and sodium chloride is table salt.
A note about the long, intimidating names for the lipids: Often people view a complex name for a molecule as a negative. This was a tactic in food marketing for a time, "choose our product, you can pronounce all of our ingredients." The length and complexity of the name actually serve a purpose in chemistry however, as it tells chemists the composition and structure of the molecule. The most commonly used nomenclature is from the International Union of Pure and Applied Chemistry (IUPAC).
Pfizer side effects
Based on reported data, the vast majority of adverse effects attributed to the Pfizer vaccination are consistent with an immune response or a direct result of the injection.
Using data from the CDC's report on Pfizer-BioNTech COVID-19 Vaccine Reactions & Adverse Events page, we see that side effects consistent with an immune response (fever 3.7%, fatigue 47.4%, and headache 41.9%) or vaccine injection (swelling 6.5%, pain 71.1%, and redness 4.7%) are fairly common. While unpleasant, the immune response from the vaccine does seem less severe than symptomatic cases of COVID-19.
Severe adverse reactions were much less frequent, with anaphylaxis occuring at a rate of 0.46 per million (FDA Decision Memo, 2020) and cases of lymphadenopathy (7 in vaccinated group agains 1 in placebo) were noted. The bigger concern is the lack of data in important subpopulations such as pregnant and lactating women and the immunocompromised. This is actually my one major concern with the clinical trials of the Pfizer vaccine, the tested population is not representative of the United States' population (see below). Non-white and older populations are under represented in the testing. This is likely not a problem as the vaccine has proven safe and effective but there is always a chance that a small subpopulation may have different reactions to drugs or vaccines and robust testing should be done if possible.
As of the writing of this article, the Pfizer, Moderna, and Johnson & Johnson vaccines appear safe and effective. Positive COVID test rates are substantially lower in the vaccinated population as are hospitalization and death rates. The key to remember with vaccines however is they are not 100% effective and combining the use of vaccinations with other good practices such as distancing and wearing a mask is the best way to resume some semblance of a normal life while keeping yourself and others safe.
References:
1. Pfizer-BioNTech COVID-19 Vaccine Overview and Safety
2. Pfizer-BioNTech COVID-19 Vaccine EUA Amendment Review and Memorandum
3. Pfizer/BioNTech COVID-19 mRNA vaccine-Overview for ACIP Meeting
