Types of COVID-19 Vaccines

How They Work: Differences and Similarities

Scientists began working to develop vaccines to prevent infection and end the pandemic very soon after the first appearance of the coronavirus (SARS-CoV-2) that causes COVID-19. However, creating a vaccine was a massive task because researchers initially knew little about the virus. Also, at first, it wasn’t even clear if a vaccine would be possible.

Since that time, researchers have made unprecedented strides. They have designed several vaccines in a much faster time frame than has ever been done before. Many different commercial and non-commercial teams around the world have used some existing and some newer strategies to approach the problem.

This article explains vaccine development, the different types of COVID-19 vaccines, and how they work. It also covers why a variety of COVID-19 vaccine types is beneficial.

Young woman getting vaccinated

Geber86/ E+/ Getty Images

General Vaccine Development Process

Vaccine development proceeds in a careful series of steps. These detailed processes ensure the final product is both safe and effective.

Research and Vaccine Trials

First comes the phase of basic research and preclinical studies in animals. After that, vaccines enter small phase 1 studies, focusing on safety. Then, more extensive phase 2 studies focus on effectiveness.

Finally, much larger phase 3 trials study a vaccine's effectiveness and safety in tens of thousands of participants. If things still look good at that point, researchers can submit a vaccine to the U.S. Food and Drug Administration (FDA) for review and potential release.

Emergency Use Authorization (EUA)

In the case of COVID-19, the FDA first approved qualifying vaccines under a specialized emergency use authorization (EUA) status. That meant they became available to some members of the public even though they hadn’t received the extensive study required for a formal FDA approval.

Even after the release of vaccines under EUA, the FDA and Centers for Disease Control and Prevention (CDC) continue to monitor any unexpected safety concerns. For example, the agencies recommended a temporary pause in using the Johnson & Johnson COVID-19 vaccine while investigating six reported cases of rare but serious blood clots.

The agencies lifted the pause after conducting a safety review. They also added information about the rare condition to fact sheets for healthcare professionals and people receiving the vaccine.

COVID-19 Vaccines

When the FDA initially approved COVID-19 vaccines, not everyone eligible could get a vaccine right away because there wasn't enough. Priority went to certain people, such as frontline workers.

As more vaccine doses became available, the CDC opened eligibility to anyone within the age groups initially authorized by the FDA.

Over 100 different vaccines worldwide have moved into clinical trials in human beings. Even more vaccines are still in the preclinical development phase (in animal studies and other laboratory research).

In the U.S., everyone 6 months and older are eligible for an mRNA COVID-19 vaccine.

Pfizer-BioNTech (Comirnaty)

The FDA's first EUA for a COVID-19 vaccine went to the one developed by Pfizer and BioNTech. Their vaccine received emergency use authorization for people 16 and older on December 11, 2020. This was based on data from its phase 3 trials.

The initial doses of the Pfizer vaccine are two 30 microgram (mcg) doses spaced 21 days apart.

On May 10, 2021, the FDA expanded the EUA for Pfizer's vaccine to include children ages 12 to 15. Kids in this age range receive the same dosage on the same schedule as people 16 and older.

In March 2021, Pfizer announced the start of trials in children ages 6 months to 11 years. On October 29, 2021, Pfizer's COVID-19 vaccine received EUA from the FDA for children ages 5 to 11. Their dose is 10 mcg, or one-third of the dosage for those 12 and older. It is also given in two doses, 21 days apart.

In June 2022, the FDA granted full approval of the Pfizer vaccine for people 12 and older. The vaccine is marketed under the name Comirnaty.

All individuals 6 months and older are now eligible to receive a Pfizer vaccine. The Pfizer vaccine for adolescents and children remains under an EUA, however.

The CDC recommends that some immunocompromised people receive an additional primary dose of the Pfizer vaccine at least four weeks after their second Pfizer dose.

Moderna (Spikevax)

On January 31, 2022, the FDA granted full approval of Moderna's COVID-19 vaccine for adults, making it the second COVID-19 vaccine approved. The vaccine is now marketed as Spikevax.

All individuals 6 months and older are now eligible to receive a Moderna vaccine. Like the Pfizer vaccine, the Moderna vaccine for adolescents and children remains under EUA.

The CDC recommends that some immunocompromised people receive an additional primary dose of the Moderna vaccine at least four weeks after their second Moderna dose.

Johnson & Johnson/Janssen (J&J)

Johnson & Johnson's COVID-19 vaccine, from its company Janssen Pharmaceuticals, was granted an EUA on February 27, 2021.

The J&J vaccine differs from Pfizer and Moderna because it is a single-dose vaccine of .5 mL.

However, the CDC recommends those who are immunocompromised receive a second dose after four weeks. Since the J&J vaccine is not approved for two doses, additional doses must be a Pfizer or Moderna vaccine.

The J&J is only approved for adults over 18. It remains under a EUA.

Due to possible side effects, the CDC recommends that people seek one of the mRNA vaccines (Moderna or Pfizer) or the Novavax vaccine over a J&J vaccine, where possible.

AstraZeneca

AstraZeneca is approved for emergency use in 90 countries. However, it is not FDA-approved for any use in the U.S.

Novavax

On July 13, 2022, the Food and Drug Administration (FDA) authorized the Novavax COVID-19 Vaccine, Adjuvanted for emergency use in individuals ages 18 and older. It is the first protein-based COVID-19 vaccine authorized in the U.S.

On September 12, 2022, the FDA extended the Novavax COVID-19 vaccine to people 12 years and older.

The CDC recommends that everyone receive an updated bivalent booster at least two months after their second Novavax dose.

Booster Shots

On August 31st, 2022, the FDA granted EUAs for updated bivalent boosters of the Moderna and Pfizer COVID-19 vaccines. Bivalent boosters have replaced all previous monovalent booster doses.

The CDC recommends an updated bivalent booster shot for all people over the age of 5, no matter the type of vaccine series initially received. A bivalent booster shot is recommended two months after receiving a primary COVID-19 vaccine series or the last booster dose. 

Children ages 5 years or older are only eligible to receive the bivalent Pfizer booster. Everyone ages 6 years and older can choose to get the Pfizer or Moderna bivalent booster. 

How Do Vaccines Work?

All the vaccines designed to target COVID-19 have some similarities.

All are made to help people develop immunity to the virus that causes the symptoms of COVID-19. That way, if a person is exposed to the virus in the future, they will have a significantly reduced chance of getting sick.

Immune System Activation

To design effective vaccines, researchers leverage the natural powers of the body’s immune system. The immune system works to identify and eliminate infectious organisms (such as viruses) in the body.

It does this in many complex ways, but specific immune cells called T cells and B cells play an essential role. T cells identify specific proteins on the virus, bind them, and ultimately kill the virus. B cells perform critical functions in making antibodies, small proteins that also neutralize and destroy the virus.

If the body encounters a new type of pathogen, either through infection or vaccination, it takes a while for these cells to learn to identify their target. That’s one reason it takes you a while to get better after becoming sick. It's also why it can take a few weeks for your body to build immunity to the virus after vaccination.

Long-Term Immunity

COVID-19 vaccines teach your body to develop long-term immunity. They do this by introducing a small amount of material from the virus to your body. This amount is not enough to make you ill. But it is enough to prompt the production of special T cells and B cells that can recognize and target the COVID-19 virus.

If these cells later encounter these same viral proteins in the wild, they get right to work because they have a "memory" of the virus and how to fight it.

In some cases, they kill the virus and shut down the infection before you ever have a chance to experience symptoms. In others, you might get a little bit sick, but not nearly as ill as you would have if your body never been exposed to the virus through vaccination.

The available COVID-19 vaccines differ in how they interact with the immune system to get this protective immunity going.

Vaccine Technology

The vaccines for COVID-19 can be broken up into two overarching categories:

  • Classical vaccines: These include live (weakened) virus vaccines, inactivated virus vaccines, and protein-based subunit vaccines.
  • Next-generation vaccine platforms: These include nucleic acid-based vaccines (such as those based on mRNA) and viral vector vaccines.

Classic vaccine methods have made almost all the vaccines for human beings currently on the market. However, all three COVID-19 vaccines authorized in the U.S. rely on newer methods.

Nucleic-Acid Based Vaccines

Newer vaccine technologies are built around nucleic acids: DNA and mRNA. DNA is the genetic material you inherit from your parents, and mRNA is a kind of copy of that genetic material used by your cell to make proteins. Both the Pfizer and Moderna vaccines utilize this newer technology.

How They Are Made

These vaccines utilize a small section of mRNA or DNA synthesized in a lab to trigger an immune response. This genetic material contains the code for the specific viral protein needed (in this case, the COVID-19 spike protein).

The genetic material goes inside the body’s cells (by using specific carrier molecules that are also a part of the vaccine). Then the person’s cells use this genetic information to produce the actual protein.

This approach sounds a lot scarier than it is. While the vaccine uses your cells to produce a protein usually made by the virus, a virus needs a lot more than that to work. So, there’s no possibility of being infected and getting sick from a DNA or mRNA vaccine.

Some of your cells will make a little COVID-19 spike protein (in addition to the many other proteins your body needs daily). That will activate your immune system to start forming a protective immune response. 

Over the past several years, researchers have worked on many different mRNA-based vaccines for infectious diseases like:

However, none of these other vaccines have reached the stage of development leading to official approval by the FDA for use in humans. The same is true of DNA-based vaccines, although some of these have been approved for veterinary uses.

Advantages

DNA and mRNA vaccines can make very stable vaccines that are very safe for manufacturers to handle. They also have the potential to make very safe vaccines that also give a solid and long-lasting immune response.

Thanks to these techniques, scientists are producing successful COVID-19 vaccines more quickly than in the past.

Disadvantages

With DNA vaccines, there is the theoretical possibility that part of the DNA might insert itself into someone's DNA. This usually wouldn't be a problem, but there is a theoretical risk of a mutation that might lead to cancer or other health issues in some cases. However, mRNA vaccines may have an even greater safety profile compared to DNA vaccines since mRNA-based vaccines don't pose that theoretical risk.

In terms of manufacturing, because these are newer technologies, some parts of the world may not have the capacity to produce or store these vaccines. However, in places where they are available, these technologies have the ability for much more rapid vaccine production than earlier methods.

mRNA COVID-19 Vaccines

Both the Pfizer and Moderna COVID-19 vaccines are mRNA-based vaccines. In addition, several other DNA and mRNA-based vaccines are currently undergoing clinical trials worldwide.

Viral Vector Vaccines

Viral vector vaccines have a lot of similarities to the vaccines based on mRNA or DNA. They just use a different mode of getting the viral genetic material into a person's cells. The Johnson & Johnson vaccine uses viral vector technology.

How They Are Made

Viral vector vaccines use part of a different virus—one genetically modified not to be infectious. Viruses are particularly good at getting into cells.

With the help of an inactivated virus (such as adenovirus), the specific genetic material encoding the COVID-19 spike protein is brought into the cells. Just as for other mRNA and DNA vaccines, the cell itself produces the protein that triggers the immune response.

Although the principle is the same, from a technical standpoint, these vaccines can fall into two categories:

  1. Replicating viral vectors (those that continue to make copies of themselves in the body)
  2. Non-replicating viral vectors (those that can't continue to make copies)

Just like other types of nucleic acid-based vaccines, you can't get COVID-19 itself from getting such a vaccine. The genetic code only contains information to make a single COVID-19 protein, one to prompt your immune system but which won't make you sick.

Advantages

Researchers have more experience with viral vector vaccines than new approaches such as those based on mRNA. For example, this method has been safely used for a vaccine for Ebola, and it’s undergone study for vaccines for other viruses such as HIV. However, it’s currently not licensed for any applications for humans in the U.S.

One advantage of this method is that it may be easier to produce a single shot method for immunization than other new vaccine technologies. In addition, compared to other newer vaccine techniques, it also may be easier to adapt for mass production at many different facilities worldwide.

Disadvantages

A disadvantage of viral vector vaccines is that the vaccine may not be as effective if a person has pre-existing immunity.

Viral Vector COVID-19 Vaccines

Johnson & Johnson's COVID-19 vaccine is a non-replicating viral vector that uses an inactivated adenovirus as the delivery method. (It is the only authorized one-shot method COVID-19 vaccine in the U.S.). In addition, the AstraZeneca vaccine (not available in the U.S.) also uses a non-replicating viral vector.

Live Virus Vaccines

A live virus vaccine uses a weakened virus to produce an immune response. These vaccines use classic technology. None of the U.S.-approved COVID-19 vaccines use this kind of technology.

How They Are Made

A live virus vaccine uses a still active and alive virus to provoke an immune response. However, the virus has been altered and severely weakened so that it causes few if any symptoms.

An example of a live, weakened virus vaccine that many people are familiar with is the measles, mumps, and rubella vaccine (MMR), given in childhood.

Advantages

Because they still have a live virus, these vaccines require more extensive safety testing.

In addition, they tend to provoke a robust immune response that lasts a long time. As a result, it’s easier to design a one-shot vaccine using a live virus vaccine than with some other vaccine types.

These vaccines are also less likely to require an additional adjuvant—an agent that improves the immune response (but which may also have its own risk of side effects).

Disadvantages

Such vaccines may not be safe if you have impaired immune systems, either from taking certain medications or certain medical conditions. They also need careful storage to stay viable.

In addition, they may be more likely to cause significant adverse events than those made by other methods.

COVID-19 Vaccines in Development

None of the U.S.-approved COVID-19 vaccines use live virus technology.

Inactivated Virus Vaccines

Inactivated virus vaccines use a killed virus to produce an immune response. These are also classic vaccines. None of the U.S.-approved COVID-19 vaccines use this technology.

How They Are Made

Inactivated vaccines were one of the first kinds of general vaccines created. They are made by killing the virus (or another type of pathogen, like a bacteria). Then the dead, inactivated virus is injected into the body.

Because the virus is dead, it can’t infect you, even if you have an underlying problem with your immune system. But the immune system still gets activated and triggers the long-term immunological memory that helps protect you if you’re ever exposed in the future.

Examples of inactivated vaccines in the U.S. include:

Advantages

Working with both inactivated and weakened virus vaccines requires specialized safety protocols. But they both have well-established pathways for product development and manufacturing.

Inactivated virus vaccines are safer and more stable to work with than live-virus vaccines.

Disadvantages

Vaccines using inactivated viruses usually require multiple doses, and they may require repeat booster doses over time. They may also not provoke quite as strong a response as a live vaccine.

COVID-19 Vaccines in Development

No vaccines undergoing clinical trials in the U.S. use either a live virus or inactivated SARS-CoV-2 virus approaches. However, several Phase 3 trials are taking place abroad that are developing inactivated virus vaccine approaches. In addition, at least one vaccine is being developed utilizing a live vaccine method.

Protein-Based Subunit Vaccines

These are also classical types of vaccines. However, there have been some newer innovations within this category. The Novavax, Adjuvanted vaccine is the first protein-based COVID-19 vaccine authorized in the U.S.

How They Are Made

Instead of using inactivated or weakened viruses, these vaccines use a part of a pathogen to induce an immune response.

Scientists carefully select a small part of the virus that will best get the immune system going. For COVID-19, this means a protein or a group of proteins. There are many different types of subunit vaccines, but all of them use this same principle. They include:

  • Specific protein purified from a live virus
  • Recombinant protein—a lab synthesized protein (the hepatitis B vaccine, for example)
  • Virus-like particles (VLPs)—multiple structural proteins from the virus, but none of the virus's genetic material (human papillomavirus (HPV), for example)

For COVID-19, almost all vaccines target a specific viral protein called the spike protein, one which seems to trigger a robust immune response. When the immune system encounters the spike protein, it responds like it would as if seeing the virus itself.

Protein-based subunit vaccines can't cause any active infection. That's because they only contain a viral protein or group of proteins, not the complete viral machinery needed for a virus to replicate.

Flu Vaccine Examples

The different versions of the flu vaccine provide a good example of the different types of classical vaccines available. Versions of it are made from:

  • Live virus
  • Inactivated virus
  • Protein subunit versions (made from purified protein and recombinant protein)

All these flu vaccines have slightly different properties in terms of their effectiveness, safety, route of administration, and their requirements for manufacturing.

Advantages

One of the advantages of protein subunit vaccines is that they tend to cause fewer side effects than those that use whole viruses (as in weakened or inactivated virus vaccines).

For example, the first vaccines against pertussis in the 1940s used inactivated bacteria. Later, pertussis vaccines used a subunit approach. These were much less likely to cause significant side effects.

Another advantage of the protein subunit vaccines is that they have been around longer than newer vaccine technologies. Their track record means that their safety is better established overall.

Disadvantages

On the other hand, protein subunit vaccines require adjuvant to boost the immune response, which can have its own potential adverse effects. And their immunity may not be as long-lasting compared to vaccines that use the whole virus. Also, they may take longer to develop than vaccines using newer technologies.

COVID-19 Subunit Vaccines

The Novavax COVID-19 vaccine, authorized by the FDA in July 2022, is a subunit vaccine (made from a recombinant protein).

The Benefits of Various COVID-19 Vaccine Technologies

Ultimately, it’s helpful to have multiple safe, effective vaccines available.

Easier To Mass Produce

Part of the reason for this is that it is impossible for any single manufacturer to quickly release enough vaccines to serve the whole world's population. Therefore, it will be much easier to perform widespread vaccination if several safe and effective vaccines are produced.

Meet Different Needs

Also, not all these vaccines will have the same properties. Hopefully, multiple successful vaccines might help meet different needs.

Some require specific storage conditions, like freezing. Some require very high-tech facilities that aren’t available in all parts of the world, but others use older techniques that can be more easily reproduced. And some will be more expensive than others.

Compare Efficacy

Some vaccines may provide longer-lasting immunity compared to some others, but that isn’t clear at this time. Some might be better for specific populations, like the elderly or people with certain medical conditions. For example, live virus vaccines will probably not be advised for anyone with problems with their immune system.

As scientists conduct more research and health officials collect more data, comparisons of the vaccines may become more apparent with time. 

Summary

Four COVID-19 vaccines are available in the U.S.—Pfizer (Comirnaty), Moderna (Spikevax), Johnson & Johnson, and Novavax. In the U.S., COVID-19 vaccines are open to everyone over 6 months old. Globally, even more vaccines are available, and more are in the development and trial phases.

Vaccines do not all use the same technology. Some utilize a live or inactivated virus. Others use protein-based subunits. Still others use DNA, mRNA, or viral vectors. The U.S.-approved COVID-19 vaccines use mRNA, viral vector, or protein-based subunit technology.

The information in this article is current as of the date listed, which means newer information may be available when you read this. For the most recent updates on COVID-19, visit our coronavirus news page.

32 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Jeyanathan M, Afkhami S, Smaill F, Miller MS, Lichty BD, Xing Z. Immunological considerations for COVID-19 vaccine strategies. Nat Rev Immunol. 2020;20(10):615-632. doi:10.1038/s41577-020-00434-6

  2. Centers for Disease Control and Prevention. Vaccine safety: overview, history, and how the safety process works.

  3. U.S. Food and Drug Administration. Emergency use authorization.

  4. Centers for Disease Control and Prevention. FDA & CDC lift recommended pause on Johnson & Johnson (Janssen) COVID-19 vaccine use following thorough safety review.

  5. Centers for Disease Control and Prevention. How CDC is making COVID-19 vaccine recommendations.

  6. World Health Organization. Draft landscape of COVID-19 candidate vaccines.

  7. Food and Drug Administration. FDA takes key action in fight against COVID-19 by issuing Emergency Use Authorization for first COVID-19 vaccine.

  8. Food and Drug Administration. Coronavirus (COVID-19) update: FDA authorizes Pfizer-BioNTech COVID-19 vaccine for emergency use in adolescents in another important action in fight against pandemic.

  9. Pfizer. Pfizer-BioNTech announce positive topline results of pivotal COVID-19 vaccine study in adolescents.

  10. Food and Drug Administration. FDA authorizes Pfizer-BioNTechCOVID-19 vaccine for emergency use in children 5 through 11 years of age.

  11. National Library of Medicine. Comirnaty label.

  12. Centers for Disease Control and Prevention. Stay up to date with your COVID-19 vaccines.

  13. Centers for Disease Control and Prevention. COVID-19 Vaccines for Moderately to Severely Immunocompromised People.

  14. Centers for Disease Control and Prevention. COVID-19 Vaccines for Moderately to Severely Immunocompromised People.

  15. Food and Drug Administration. Janssen COVID-19 vaccine.

  16. Centers for Disease Control and Prevention. Janssen COVID-19 vaccine (Johnson & Johnson).

  17. Center for Disease Control and Prevention. Overview of COVID-19 Vaccines.

  18. AstraZeneca. Two billion doses of AstraZeneca's COVID-19 vaccine supplied to countries across the world less than 12 months after first approval.

  19. Food and Drug Administration. Coronavirus (COVID-19) update: FDA authorizes emergency use of Novavax COVID-19 vaccine, adjuvanted.

  20. Food and Drug Administration. Novavax COVID-19 Vaccine, Adjuvanted.

  21. Centers for Disease Control and Prevention. Stay Up to Date with Vaccines.

  22. Centers for Disease Control and Prevention. Understanding how COVID-19 vaccines work.

  23. van Riel D, de Wit E. Next-generation vaccine platforms for COVID-19. Nat Mater. 2020;19(8):810-812. doi:10.1038/s41563-020-0746-0

  24. Centers for Disease Control and Prevention. Different COVID-19 vaccines.

  25. Pardi N, Hogan MJ, Porter FW, Weissman D. mRNA vaccines - a new era in vaccinology. Nat Rev Drug Discov. 2018 Apr;17(4):261-279. doi:10.1038/nrd.2017.243

  26. Wang J, Peng Y, Xu H, Cui Z, Williams RO 3rd. The COVID-19 vaccine race: challenges and opportunities in vaccine formulation. AAPS PharmSciTech. 2020;21(6):225. doi:10.1208/s12249-020-01744-7

  27. Kaur SP, Gupta V. COVID-19 vaccine: a comprehensive status report. Virus Res. 2020;288:198114. doi:10.1016/j.virusres.2020.198114

  28. Ura T, Okuda K, Shimada M. Developments in viral vector-based vaccines. Vaccines. 2014;2(3):624-641. doi:10.3390/vaccines2030624

  29. Centers for Disease Control and Prevention. Johnson & Johnson's Janssen COVID-19 overview and safety.

  30. National Institute of Allergy and Infectious Disease. Vaccine types.

  31. Centers for Disease Control and Prevention. How influenza (flu) vaccines are made.

  32. Novavax. Coronavirus vaccine candidate updates.

By Ruth Jessen Hickman, MD
Ruth Jessen Hickman, MD, is a freelance medical and health writer and published book author.