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

Using this strategy, viruses are weakened so they reproduce very poorly once inside the body. The vaccines for measles, mumps, German measles (rubella), rotavirus, oral polio (not used in the U.S.), chickenpox (varicella), and influenza (intranasal version) vaccines are made this way. Viruses usually cause disease by reproducing themselves many times in the body. Whereas natural viruses reproduce thousands of times during an infection, vaccine viruses usually reproduce fewer than 20 times. Because vaccine viruses don't reproduce very much, they don't cause disease, but vaccine viruses replicate well enough to induce "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 provide immunity that is usually life-long. The limitation of this approach is that these 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

Using this strategy, viruses are completely inactivated (or killed) with a chemical. By killing the virus, it cannot possibly reproduce itself or cause disease. The inactivated polio, hepatitis A, influenza (shot), and rabies vaccines are made this way. Because the virus is still "seen" by the body, cells of the immune system that protect against disease are generated.

There are two benefits to this approach:

• 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

However, the limitation of this approach is that it typically requires several doses to achieve immunity.

Use part of the virus

Using this strategy, just one part of the virus is removed and used as a vaccine. The hepatitis B, shingles, human papillomavirus (HPV), and one of the influenza vaccines are made this way. The vaccine is composed of a protein that resides on the surface of the virus. This strategy can be used when an immune response to one part of the virus (or bacteria) is responsible for protection against disease.

These vaccines can be given to people with weakened immunity and appear to induce long-lived immunity after two 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 them with a chemical (the toxin, once inactivated, is called a toxoid). By inactivating the toxin, it no longer causes disease. The diphtheria, tetanus and pertussis vaccines are made this way.

Another strategy to make a bacterial vaccine is to use part of the sugar coating (or polysaccharide) of the bacteria. Protection against infection by certain bacteria is based on immunity to this sugar coating (and not the whole bacteria). However, because young children don't make a very good immune response to the sugar coating alone, the coating is linked to a harmless protein (this is called a "conjugated polysaccharide" vaccine). The Haemophilus influenzae type B (or Hib), pneumococcal, and some meningococcal vaccines are made this way.

Two meningococcal vaccines, which prevent one particular type of the bacterium (type B) not contained in the other meningococcal vaccines, are made using two or more proteins from the bacteria, not the bacterial polysaccharide.

Just like for inactivated viral vaccines, bacterial vaccines can be given to people with weakened immune systems, but 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. Some of the vaccines for COVID-19 are made this way.

mRNA vaccines

The COVID-19 messenger RNA (mRNA) vaccine contains mRNA that is the code, or blueprint, for the spike protein of the SARS-CoV-2 virus. The vaccinated person’s dendritic cells use the blueprint to make the spike protein from the surface of the virus. Once the immune system realizes this protein is “foreign,” it creates an immune response against it, including immunologic memory, so the next time, the person is exposed to the virus, the immune system is ready to respond rapidly. Similar to vaccination strategies that inject parts of a virus directly, 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 require two doses to be protective. The Pfizer and Moderna COVID-19 vaccines are made this way.

• 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, and the immune system, recognizing it is “foreign,” responds to protect the body and create immunologic memory. Currently, no DNA vaccines are commercially available.

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

Vector virus vaccines (e.g., adenovirus-based vaccines)

Another way to deliver the gene that codes for the coronavirus spike protein is to put that gene into a virus that can’t reproduce itself but can still enter cells and deliver the needed gene. This strategy is being used in so-called replication-deficient human or simian adenovirus vaccines. Although adenoviruses can cause disease in people, these vectored viruses are engineered so that they can’t cause disease; as such, they can be given to people who are immune-compromised.

The Johnson & Johnson (J&J)/Janssen and AstraZeneca (AZ) COVID-19 vaccines are made this way. The J&J/Janssen vaccine is given as one dose and the AZ vaccine is given as two doses.