How Do COVID-19 Vaccines Work?

Currently, there are 96 candidate vaccines for COVID-19, with 27 candidate vaccines in stage 3 clinical trials. So far,13 vaccines have been authorized across multiple countries, and as of May 10th, 3 vaccines have been authorized and recommended for use in the United States: Pfizer-BioNTech, Moderna, Johnson & Johnson.


Differing in how they provide immunity to the virus that causes COVID-19, there are four types of COVID-19 vaccines: mRNA, non-replicating viral vector, protein subunit, and inactivated whole virus.


1. mRNA vaccine

Both Pfizer-BioNTech and Moderna are mRNA vaccines developed for COVID-19. These vaccines provide messenger RNA (mRNA) that encodes for a piece of the virus’s “spike protein.” Separated from the rest of the virus, this protein piece is completely harmless; it is not strong enough to cause infection and is easily identified by one’s immune system. The mRNA, following injection, enters cells, which then uses the mRNA to make the protein piece. Next, the cell displays the protein piece on its surfaces. Immune cells, recognizing the protein piece as “foreign,” begin producing antibodies specific to the protein piece, identical to what happens in a natural infection against COVID-19. Having built an immune response to a ubiquitous element of COVID-19, the body has learned how to protect against future COVID-19 infections.


2. Non-replicating viral vector vaccine

Currently in Phase 3 clinical trials, Oxford-AstraZeneca is an example of a viral vector vaccine, which works similarly to mRNA vaccines. In this type of vaccine, genetic material from the COVID-19 virus is inserted into a weakened live virus vector, which enables entry into a host cell. After the vector enters a host cell, the cell will use the instructions encoded in the virus’s genes to produce copies of the harmless S protein associated with the COVID-19 virus. S proteins are then presented on the cell’s exterior surface. Once immune cells recognize the S proteins as antigens, the host’s immune system responds by creating antibodies and white blood cells that can respond quickly upon a COVID-19 infection.


3. Protein subunit vaccine

The Novavax vaccine is an example of a protein subunit vaccine. In this type of vaccine, isolated protein fragments of SARS-CoV2 are injected into the body. The pieces have been carefully studied to determine which combinations are able to trigger effective immune response. Once isolated, these fragments are considered “purified” since they do not have the virus’s full structure; thus, their function is limited and side effects are minimized. But, the protein subunits would still be able to trigger an immune response and keep one protected from future SARS-CoV-2 virus.


4. Whole virus vaccine

Both Sinopharm and Sinovac are examples of an inactivated virus vaccine. Unlike mRNA, viral vector, and protein subunit vaccines, inactivated vaccines contain the entire SARS-CoV-2 virus. However, the virus is chemically modified to be inactivated, removing its ability to self-replicate. Thus, the vaccine cannot cause a COVID-19 infection. Like the other vaccines described, the body’s immune system “memorizes” the foreign viral particles, providing protection against future COVID-19 infections. Because inactivated viruses usually produce a weaker immune response than other types of vaccines, adjuvants (which increase the immune response to a vaccine) and booster shots are used to generate a stronger, longer-lasting immunity to the virus.


All four types of vaccines provide protection against natural COVID-19 infection. Given that the four differ in how they prepare your immune system, you may be wondering which vaccine works best for you. For this, we defer to the CDC’s advice:


The best COVID-19 vaccine is the first one that is available to you. Do not wait for a specific brand. All currently authorized and recommended COVID-19 vaccines are safe, effective, and reduce your risk of severe illness.


For help finding COVID-19 vaccines near you, visit vaccines.gov.


For more information about vaccines:

Understanding How COVID-19 Vaccines Work | CDC

Different types of COVID-19 vaccines: How they work - Mayo Clinic



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