This week’s articles on COVID-19 will focus on how the COVID-19 vaccines work and how they are both similar and different from other vaccines. In these articles I can only scratch the surface of these topics. If you are interested in a specific question, you would like me to address in future articles, please email it to healthmattersquestions@gmail.com. I will also start including with a set of resources that you can look to for more information. Statements in these articles should be considered coming from myself, not from any organization I represent or my employer. Information presented is intended to provide a medical perspective - the articles are not intended as a political statement for or against any public policy.
Do the COVID-19 vaccines work differently than other vaccines?
Yes and no. All vaccines do one basic thing; they work with our immune system to help protect us against harm. A vaccine gives our immune system a chance to prepare for specific infections. There are many different ways vaccines can accomplish this goal. For example, the first successful vaccine developed against polio was a drink containing a weakened form of the virus that causes polio. The first polio vaccine used in the US was an injection of inactivated (“dead”) virus.
Many vaccines that we use today against diseases use only a part of the bacteria or virus. Examples of what we call subunit vaccines are the vaccines that protect us against the hepatitis B virus and meningococcal bacteria. When you get a tetanus shot you are gaining protection against disease by a different approach. You gain protection by being exposed to a harmless version of the toxin that tetanus bacteria produce.
The three COVID-19 vaccines that are in use in the United States do not contain SARS-CoV-2 or any piece of the virus. Instead, they have the genetic blueprints for our body to make a replica of just one part of the virus. The Moderna and Pfizer-BioNTech vaccines use mRNA for the blueprints packaged inside of tiny globules of fat. The vaccine developed by Janssen Pharmaceuticals which is owned by Johnson & Johnson has DNA that is delivered through a harmless virus. All of the COVID-19 vaccines have the same end result. They protect you against disease by giving your immune system a chance to prepare for the virus. This protection is strengthened when you get a second or third dose of the vaccine.
What are the Moderna and Pfizer-BioNTech vaccines made of and how do they work?
The Moderna and Pfizer-BioNTech vaccines are very similar and for the purpose of this article can be considered to be the same. They make use of a vaccine technology that has been studied and developed over decades. These vaccines use a substance found in every animal, plant, and microorganism (except some viruses). RNA like DNA is a long chain of 4 basic biomolecules. DNA contains all the information needed for making all the proteins our bodies produce. There are several different versions of RNA. Messenger RNA (mRNA) carries transcribed coding sequences from our DNA to make proteins. Messenger RNA delivers this code to our protein making machinery to produce the countless number of structures, enzymes, hormones, and other proteins essential to life.
These vaccines have mRNA packaged up into tiny little particles of lipids. These globules are composed of layers of fatty substances such as cholesterol and polyethylene glycol. Polyethylene glycol also known as PEG has many different forms and has been used in a number of foods and medications. One form of PEG is a common medication available over the counter - the brand name of this laxative is Miralax. Allergies to PEG are rare but have occurred. If you have a true allergy to polyethylene glycol you should receive the Johnson and Johnson vaccine instead of the Moderna or Pfizer-BioNTech vaccines.
Using fat globules to deliver medications is not new. Fatty globules have been used since the 1960’s although these fat globules were larger than what is used for the mRNA vaccine. The first drug to be approved in the US to use microscopic lipid particles like those used for mRNA vaccines was approved for use back in 2018.
After the mRNA containing tiny globules of fat are injected, cells that are specialized at picking up viruses and other intruders engulf the fat and mRNA. Once inside the cell, the mRNA interacts with our protein making machinery to make replicas of the protein the virus uses to get into our cells. These proteins are similar but not exact copies of the virus spike protein. One key change in the structure of the replicas is that they are “locked in” to the shape of the virus spike protein has before it enters our cells. When the SARS-CoV-2 virus spike protein connects with the surface protein on our cells the spike protein undergoes changes in structure before it can enter our cells. The replica of the spike protein that our bodies make from the mRNA has small changes in sequence of the protein's building blocks which keep it from undergoing that change.
The cells that pick up the mRNA containing lipid particles belong to a special group of immune cells called “professional antigen presenting cells”. Antigens are anything that our bodies could potentially mount an immune response to such as viruses or bacteria. These cells have the job of presenting pieces of the invader to other cells in our immune system.
The spike protein replica or pieces of it are displayed on the cell surface of the antigen presenting cells. When other specialized cells of the immune system encounter these antigens, a complex process occurs. The end result is the proliferation of a number of different immune system cells including those that make antibodies. Antibodies are produced to not just one part of the spike protein but multiple parts so even if the spike protein changes through mutations, we will still likely have antibodies that will still bind to parts of the spike protein.
A lot of the activity of immune cells interacting with each other and making copies of themselves occurs in lymph nodes such as the ones in our armpits. That is why many people will get swollen sore armpits in the same arm that they got the shot.
In addition to the cells that start making antibodies are other antigen specific cells that are directly involved in fighting infections. “Memory cells” that are specific to the spike protein can persist for months or years are also produced.
The immune system processes that are occurring require a lot of communication between all these different immune system cells as well as with the rest of the body. Many different substances are secreted by the immune cells in this process. These substances are part of why we might get a headache, feel achy or have a fever after getting vaccinated.
The mRNA vaccines for COVID-19 are the first mRNA vaccines to be used in the United States general population. However, several different mRNA vaccines have been developed or are in development for other diseases. The FDA in 2019 approved a mRNA vaccine against the Ebola virus. In 2017 human clinical trials with mRNA Rabies and Zika virus vaccines were started.
In December of 2019 the biotech company Moderna submitted an application to the FDA to begin human trials for a vaccine against a virus that causes periodic outbreaks of disease in southeast Asia. On the application to the FDA for this mRNA vaccine against the Nipah virus, Moderna stated they intended to begin the trial on February 18, 2020.
Then came COVID-19. As soon as the SARS-CoV-2 genetic sequence was published on January 11, 2020; a team of scientists from Moderna and the NIH went to work on developing the mRNA sequence that would become the Moderna vaccine. The team had a head start. Work on vaccines for related viruses that caused MERS and SARS had identified the spike protein as the target for a vaccine. Moderna was able to quickly shift from making a vaccine against the Nipah virus to one against SARS-CoV-2. On March 16th, 2020 the Moderna vaccine was being injected into the arms of participants in phase 1 clinical trials. The biotechnology company BioNTech also hit the ground running as they had been working for many years on the science of mRNA therapies.
How does the Johnson and Johnson vaccine differ from the Moderna and Pfizer-BioNTech vaccines?
The vaccine developed by Janssen Pharmaceuticals which is owned by Johnson & Johnson is what is referred to as a “viral vector vaccine”. DNA that codes for a replica of the spike protein is delivered by inserting into a virus that will not cause us harm. Once the virus is taken up by cells the DNA is transcribed into mRNA. After that the process by which the vaccine gives us protection is the same as it is with the mRNA vaccines.
Viral vector vaccines have been used to control Ebola. Viral vector vaccines are currently being studied for protection against influenza, HIV and Zika viruses.
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