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How the New COVID Vaccines Compare to Other Viral Vaccines
The leading vaccines against SARS-CoV-2 are based on a new technology that delivers mRNA to cells. This novelty, combined with political and social division, has resulted in a fair amount of nonsense commentary about them. The AstraZeneca and Johnson & Johnson vaccines are also somewhat novel. I thought I would quickly put these new technologies into perspective by comparing them to other viral vaccine technologies.
The first thing you need to know is that the principal purpose of a genome is to store the sequence information for all kinds of different proteins. Our genome is made of DNA, but it does not directly make the proteins. Rather, a similar intermediate molecule called messenger RNA (mRNA) is produced from DNA, and it is the mRNA that is directly read by the cell's machinery to make proteins. DNA -> mRNA -> protein. (Additional variation on this scheme can be found among viruses, but RNA -> protein always holds.)
Next, the immune system can be conceptually divided into two arms that work together: innate and adaptive. The innate system responds in ways that are not specific to a pathogen (disease-causing microbe). It's what makes you feel lousy and gives you a fever, and it kicks in quick. The adaptive immune system takes longer to respond, but produces antibodies and other cells that specifically target a pathogen. The value of vaccines comes from their ability to engage the adaptive immune system such that it is ready to go when the actual pathogen shows up. When we talk about being immune to something, we're really talking about the adaptive immune response.
In order to gain immunity, the immune system needs to come in contact with components (usually proteins) of the pathogen. There are several ways of doing this. I've listed the basic strategies for viruses along with some well-known examples in human medicine. Almost all of them are also used in veterinary medicine. There are some further variations to these strategies, but I think this captures the major themes.
1. Infect someone with a weakened virus that does not cause disease. The virus commandeers the cells to produce viral proteins (via viral mRNAs). This is the oldest and classic strategy. (Examples: smallpox, measles, mumps, rubella, yellow fever, and oral polio.)
2. Inject a virulent virus that has been inactivated such that it cannot replicate. This is also a relatively old method. (Example: injected polio, hepatitis A)
3. Inject purified viral proteins. (Example: hepatitis B)
4. Inject virus-like particles (VLPs). These are essentially virus particles that do not have any genome, and thus no ability to replicate or produce more viral protein. (Example: HPV)
5. Use a different non-pathogenic virus as a Trojan horse to make proteins of the virus of interest. (Examples: the AstraZeneca and Johnson & Johnson COVID-19 vaccines are, I believe, the first approved human vaccines of this type. However, this strategy is used in a number of veterinary vaccines.)
6. Inject DNA that codes for viral proteins. DNA -> mRNA -> protein. (Doesn't seem to work well in humans, so it is not used in human vaccines. But there are a few examples in veterinary use.)
7. Inject mRNA that codes for viral proteins. This is the newest technology, first used by Moderna and Pfizer/BioNTech. The challenge of this method has been to deliver RNA to cells, since RNA is easily degraded. The technology advancement has been figuring out how to encapsulate the RNA in lipid nanoparticles such that the RNA is protected until it is delivered inside the cell.
In each of these cases, the adaptive immune system is exposed to viral proteins--proteins that were either produced by the body's cells, or were produced by cell culture prior to injection. mRNA vaccines are the cleanest vaccines in the sense that they don't involve any extraneous viral proteins or genetic material. They really get to the heart of the process: mRNA -> protein, and it's exciting to envision how they might be applied to other diseases.
Each method has pros and cons, and has to be matched to the biology of the virus and the resulting immune response. For example, in some cases antibodies directed against a single protein are sufficient to give you immunity. In other cases it's not that simple, so you wouldn't use a strategy that only delivers a single protein. But in every case, it really boils down to exposing the immune system to the right viral proteins in the right way.
