Several basic strategies are used to make vaccines, as shown in this infographic. The strengths and limitations of each approach are described here.

Weaken the virus

Viruses are weakened, so they reproduce very poorly once inside the body. Vaccines for measles, mumps, rubella, rotavirus, polio (oral version; not used in the U.S.), chickenpox (varicella), and influenza (intranasal version) vaccines are made this way. These are all vaccines that protect against viruses. Viruses cannot reproduce on their own. They need cells from other organisms to make more virus particles. Viruses reproduce thousands of times during a natural infection, meaning an infection that occurs after exposure to the virus in the community. 

Live, weakened vaccine viruses usually reproduce fewer than 20 times. This is enough times to cause immunity, but not enough to cause disease. The immune response generates "memory B cells" that protect against infection in the future. Find out more about these and other cells of the immune system.

The advantage of live, weakened vaccines is that one or two doses usually lead to life-long immunity. The limitation of this approach is that these kinds of vaccines usually cannot be given to people with weakened immune systems (like people with cancer or AIDS). Find out more about what happens when the immune system doesn’t work properly.

Watch this video to see how viruses are weakened to make vaccines.

Inactivate the virus

Viruses are completely inactivated (or killed) with a chemical. Killing the virus prevents it from reproducing itself or causing disease. Examples include the polio (shot version), hepatitis A, influenza (shot version), and rabies vaccines. Because the immune system defends against the dead virus, it generates immunity that can protect the person if they are exposed to the virus in the future.

Two benefits to this approach include:

• The vaccine cannot cause even a mild form of the disease that it prevents.
• The vaccine can be given to people with weakened immune systems.

A limitation of this approach is that it typically requires several doses of the vaccine to develop protective immunity.

Use part of the virus

Part of the virus is used as the vaccine. Examples include the hepatitis B, shingles, human papillomavirus (HPV), and one of the influenza vaccines. This approach can be used when an immune response to one part of the virus can protect against disease. Usually, this type of vaccine is made from one or more proteins found on the surface of the virus.

These vaccines can be given to people with weakened immunity and appear to induce long-lived immunity after a couple of doses.

Watch this video to see how genetic engineering is used to make effective vaccines.

Use part of the bacteria

Some bacteria cause disease by making a harmful protein called a toxin. Several vaccines are made by taking toxins and inactivating (killing) them with a chemical. The inactivated toxin is called a toxoid. A toxoid can no longer cause disease. The diphtheria, tetanus and pertussis vaccines are made this way.

Other bacteria have a sugar coating (or polysaccharide), and protection against infection requires immunity to this sugar coating (and not the whole bacteria). Young children don't make a very good immune response to these sugar coatings, so scientists have found a way to attach a harmless protein to the sugar coating. These are called "conjugated polysaccharide" vaccines, and they allow young children to generate protective immunity after vaccination. The Haemophilus influenzae type b, pneumococcal, and some meningococcal vaccines (called MenACWY) are made this way.

The meningococcal vaccines for meningococcus type B are made using two or more proteins from the bacteria, not the sugar coating.

Bacterial vaccines made in these ways can be given to people with weakened immune systems, but they often require several doses to induce adequate immunity.

Provide the genetic code (DNA, mRNA, or vectored viruses) for part of the virus

Using this strategy, the person who is vaccinated makes part of the virus and their immune system responds to generate immunity. 

mRNA vaccines

These vaccines deliver mRNA that is the code, or blueprint, for the part of the virus that we need an immune response against for protection. Examples include some COVID-19 and respiratory syncytial virus (RSV) vaccines. The COVID-19 vaccines deliver mRNA for the spike protein of the SARS-CoV-2 virus. The RSV vaccine delivers mRNA for a surface protein that is needed for the virus to attach to cells. 

Once a person gets vaccinated, immune system cells, called dendritic cells, use the mRNA blueprint to make the protein. When the immune system realizes the protein is “foreign,” it creates an immune response against it. Part of the immune response includes making immunologic memory, so the next time the person is exposed to the virus, the immune system is ready to respond rapidly. 

This strategy can be used when an immune response to one part of the virus is capable of protecting against disease.

These vaccines can be given to people who are immune-compromised but may require more than one dose to be protective. 

• Watch this animation to see how mRNA vaccines work.
• Listen to Dr. Offit explain mRNA vaccines in this short video.

DNA vaccines

DNA vaccines deliver the genetic code from which mRNA is made. The mRNA then serves as the blueprint for making the viral protein. As with mRNA vaccines, the immune system recognizes the protein as “foreign” and responds to protect the body and create immunologic memory. Currently, no DNA vaccines are commercially available in the U.S.

• Listen to Dr. Offit explain DNA vaccines in this short video.

Vector virus vaccines 

Another way to deliver genetic material is to put the gene for the virus protein into another virus, called a vector virus. The vector virus doesn’t cause disease, but it can enter cells and deliver the needed gene. Examples include some COVID-19 vaccines (none used in the U.S.) and the Ebola vaccine. 

These vaccines can be given to people who are immune-compromised.