Table of ContentsView AllTable of ContentsVaccine DevelopmentAvailable OptionsHow They WorkNucleic-Acid Based VaccinesViral Vector VaccinesLive Virus VaccinesInactivated Virus VaccinesProtein-Based Subunit VaccinesBenefits
Table of ContentsView All
View All
Table of Contents
Vaccine Development
Available Options
How They Work
Nucleic-Acid Based Vaccines
Viral Vector Vaccines
Live Virus Vaccines
Inactivated Virus Vaccines
Protein-Based Subunit Vaccines
Benefits
Scientists began working to develop vaccines to prevent infection and end the pandemic very soon after the first appearance of thecoronavirus(SARS-CoV-2) that causes COVID-19. However, creating avaccinewas 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.
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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.
COVID-19 Vaccine
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.
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 theJohnson & Johnson COVID-19 vaccinewhile 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:Stay up to date on which vaccines are available, who can get them, and how safe they are.
COVID-19 Vaccines
When the FDA initially authorized COVID-19 vaccines, not everyone eligible could get a vaccine right away because there wasn’t enough. Prioritywent to certain people, such as frontline workers.
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 is eligible for a COVID-19 vaccine.
In October 2022, the CDC’s Advisory Committee on Immunization Practices (ACIP) approved adding COVID-19 vaccination to the immunization schedules for children and adults. The updated schedules including COVID-19 vaccines were then published in February 2023.
Pfizer-BioNTech (Comirnaty)
The initial doses of the Pfizer vaccine are two 30 microgram (mcg) doses spaced 21 days apart.
In July 2022, theFDA granted full approvalof the Pfizer vaccine for people 12 and older.For eligible vaccine recipients younger than 12, the vaccine remained available under an EUA. The vaccine is marketed under the nameComirnaty.
The CDC recommends that some high-risk groups, including immunocompromised people receive an additional dose of the Pfizer vaccine at least four weeks after their second Pfizer dose.
The composition of the vaccine has been updated since the initial version. First, in 2022, a bivalent version was created protecting against the original SARS-CoV-2 strain and omicron variants circulating at that time. Then, in 2023, another update dropped the original strain and contained components of only a newer omicron strain.
Moderna (Spikevax)
Like the Pfizer vaccine, the Moderna mRNA vaccine was first granted an EUA before it was fully approved. 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 asSpikevax.
All individuals 6 months and older are now eligible to receive a Moderna vaccine.
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.
As with the Pfizer vaccine, updated versions have since been created targeting the predominant virus strains in circulation.
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. Updated vaccines have been authorized each year since, targeting the predominant omicron variant.
Johnson & Johnson/Janssen (J&J)
Johnson & Johnson’s COVID-19 vaccine, from its company Janssen Pharmaceuticals, was granted an EUA on February 27, 2021.However, the J&J vaccine is no longer available in the U.S. after all remaining stock of the vaccine expired on May 7, 2023.
The J&J vaccine differs from Pfizer and Moderna because it is a single-dose, viral vector vaccine.
AstraZeneca
AstraZeneca’s vaccine is approved or authorized for emergency use in over 100 countries. However, it is not FDA-approved for any use in the U.S.The vaccine is marketed as Vaxzevria.
Booster Shots and Updated Formulas
The first booster shot authorized for use was the Pfizer vaccine, in September 2021. The following month, Moderna’s vaccine was also granted EUA for use as a booster.
The FDA has authorized updated formulas each year, based on recommendations from the FDA’s Vaccines and Related Biological Products Advisory Committee. For example, the committee recommended that the 2024-2025 vaccine formulas target the KP.2 strain that became dominant in 2024. Both of the mRNA vaccines were updated to target this strain and the Novavax vaccine was updated to target the parent of the KP.2 strain, called JN.1.
The CDC recommends that everyone age 6 months and older receive an updated vaccine. Those who are immunocompromised may receive additional doses.
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 ofCOVID-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’simmune 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 andB cellsplay an essential role. T cells identify specific proteins on the virus, bind them, and ultimately kill the virus. B cells perform critical functions in makingantibodies, 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
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:
Classic vaccine methods have made almost all the vaccines for human beings currently on the market. However, three of the four COVID-19 vaccines that have been authorized in the U.S. rely on the newer methods.
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).
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:
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 VaccinesBoth 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.
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 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.
Viral vector vaccines use part of adifferentvirus—one genetically modified not to be infectious. Viruses are particularly good at getting into cells.
With the help of aninactivatedvirus (such asadenovirus), 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:
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.
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 forEbola, 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.
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 VaccinesJohnson & Johnson’s COVID-19 vaccine is a non-replicating viral vector that uses an inactivated adenovirus as the delivery method.The AstraZeneca vaccine also uses a non-replicating viral vector. Neither vaccine is available in the United States.
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.The AstraZeneca vaccine also uses a non-replicating viral vector. Neither vaccine is available in the United States.
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.
Alive virus vaccineuses 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. These vaccines are also called live-attenuated vaccines.
An example of a live, weakened virus vaccine that many people are familiar with is themeasles, mumps, and rubella vaccine (MMR), given in childhood.
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 additionaladjuvant—an agent that improves the immune response (but which may also have its own risk of side effects).
Such vaccines may not be safe if you haveimpaired immune systems, either from taking certain medications or certain medical conditions.They also need careful storage to stay viable.
COVID-19 Vaccines in DevelopmentNone of the U.S.-approved COVID-19 vaccines use live virus technology.
COVID-19 Vaccines in Development
None of the U.S.-approved COVID-19 vaccines use live virus technology.
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.
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:
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.
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 DevelopmentSeveral COVID-19 vaccines made using this approach have been approved outside of the U.S., like Sinovac’s CoronaVac. Numerous inactivated virus vaccines are under development, including one undergoing clinical trials in the U.S.
Several COVID-19 vaccines made using this approach have been approved outside of the U.S., like Sinovac’s CoronaVac. Numerous inactivated virus vaccines are under development, including one undergoing clinical trials in the U.S.
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.
Instead of using inactivated or weakened viruses, these vaccines use apartof 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:
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 ExamplesThe 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 virusInactivated virusProtein subunit versions (made from purified protein and recombinant protein)
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 virusInactivated virusProtein subunit versions (made from purified protein and recombinant protein)
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:
All these flu vaccines have slightly different properties in terms of their effectiveness, safety, route of administration, and their requirements for manufacturing.
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.
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 Benefits of Various COVID-19 Vaccine Technologies
Ultimately, it’s helpful to have multiple safe, effectivevaccinesavailable.
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 specificstorage 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 thevaccinesmay become more apparent with time.
Summary
Three COVID-19 vaccines are available in the U.S.—Pfizer (Comirnaty), Moderna (Spikevax), and Novavax. In the U.S., updated 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 or protein 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 ourcoronavirus news page.
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