July 28, 2022


Seth Toback, MD HeadshotScientists around the world are using multiple approaches to develop vaccines to help protect against SARS-CoV-2, the coronavirus that causes COVID-19. Special thanks to Seth Toback, MD, senior vice president, global medical lead at Novavax, Inc., for this guest blog post on the differences between current COVID-19 vaccine technologies.

With new vaccines being approved across the globe, it is a daunting challenge to keep up with the names, manufacturers, and all the data from various clinical trials. One somewhat helpful fact is that although there are many vaccines, there are only a limited number of vaccine technologies used in all of them—none of which can cause COVID-19.

They all build SARS-CoV-2 spike protein, but a few simple analogies can help explain the various technologies currently being used. Like a toolbox with different tools, COVID-19 vaccines use different methods and mechanisms to create spike protein to which the body responds by making protective antibodies. These antibodies and other immune system cells are what protect you when you encounter the virus at a later point in time.

mRNA vaccines, such as the Moderna and Pfizer vaccines, work by supplying the blueprints for the spike protein in the form of genetic material. This newer technology has been used with great success so far in the fight against COVID-19, partly owing to the speed in which the blueprints can be drawn up and the high efficacy of the resulting vaccines.


Viral vector COVID-19 vaccines, such as the J&J/Janssen vaccine, send in a “helpful guide” that instructs the immune system. These vaccines use another, harmless virus that is good at entering human cells to deliver blueprints to instruct your cells on how to build immunity to the virus that causes COVID-19. Vaccines using this technology have been used with good results.

Protein-based vaccines, such as the Novavax vaccine, use a different tactic. These vaccines utilize critical fragments or proteins from the virus and deliver them straight to your body. Manufacturers use a factory other than the human body, typically insect or plant cells, which are highly efficient at producing the protein fragments that the body needs to recognize in order to fight the disease. Protein-based vaccines have been used for decades, including some types of influenza (flu) vaccines, tetanus vaccines, and some hepatitis B vaccines.

Live or inactivated COVID-19 vaccines are made from whole SARS-CoV-2 viruses that are either weakened or killed. Several vaccine candidates using this technology are currently in pre-clinical and clinical development stages. When these weakened viruses are delivered to the body, the body responds by making protective antibodies. This technique, which is the traditional way of making vaccines, might seem like the simplest method and sometimes it can be. Yet, making live but weakened vaccines can be a slow process, and killing a whole virus has been associated with some side effects in previous inactivated vaccines. Another limitation of inactivated vaccines is that they are generally somewhat less effective than other vaccines.

More Arrows in the Quiver

Some vaccines are easy to ship, store, and administer. Other vaccines can be manufactured quickly or can quickly be changed to address new variants circulating. Still other vaccines have different degrees of side effects or the potential for rare serious adverse effects. Equally important is providing individuals a choice in selecting which COVID-19 vaccine to get, based on their own perception of potential risks and benefits.

Although not all COVID-19 vaccines are licensed and available in every country, in countries where more than one vaccine is available, vaccine choice is another arrow in the quiver to help overcome vaccine hesitancy—either hesitancy to accept a specific type of vaccine or hesitancy to accept a booster vaccine after experiencing side effects from the initial vaccine series.

More vaccine options and more tools in the toolbox will help us to vaccinate everyone against SARS-CoV-2, because no one is safe until we are all safe.

Learn More about COVID-19 Vaccines

Side Effects

For additional information about COVID-19 vaccines, view these resources from the National Foundation for Infectious Diseases (NFID) and other sources:

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