Nearly 160 COVID-19 vaccine candidates are in development. Although all approaches are distinct, they are based on a few simple strategies. Here's a closer look at how they work.

Traditional approaches

Some researchers are attempting to use the entire SARS-CoV-2 coronavirus to induce a broad immune response, knowing that minor viral infections can inoculate patients against more serious disease. An advantage of these methods is their proven efficacy. They have helped defeat polio, hepatitis A, rabies and other diseases. But working with a live virus is risky, these vaccines are challenging to create, and production is time-consuming.

Live attenuated virus vaccine

Developed in 1937 by virologist Max Theiler to create a yellow fever vaccine, this protocol takes a live virus and introduces it to mice, chicken embryos or other nonhuman species. As the virus becomes more successful at replicating in nonhuman cells, it loses its ability to replicate in human cells. When introduced back into the human body, attenuated viruses still trigger an attack by the immune system. Such vaccines provide protection against measles, mumps, rubella, chickenpox and one type of rotavirus.

Inactivated virus vaccine

This protocol, pioneered by Jonas Salk in the early 1950s, takes live viruses and kills them so they can't replicate. The inactivated, or dead, virus is injected into the body, which prompts the creation of antibodies. Inactivated virus vaccines often require periodic booster shots. This protocol was used to create Salk's injectable polio vaccine, and the hepatitis A and rabies vaccines.

Newer approaches

Many researchers are hoping that a single protein on the coronavirus' surface can do the job. Disable the so-called spike protein, or S protein, the theory goes, and the virus can't access the host cell. But some researchers worry that if the S protein mutates, the vaccine will be ineffective.

Viral vector vaccine

Researchers splice genetic instructions for making the S protein into a harmless virus, which is then injected into the body. The virus uses human cells to mass-produce the protein, and the immune system attacks the virus and the protein with antibodies. Sometimes the harmless virus has been modified so that it cannot replicate inside the body. Non-replicating viruses might require higher doses or booster shots. Researchers used this approach to develop an Ebola vaccine.

Virus-like particle vaccine

Researchers are trying to develop a "particle" that resembles the coronavirus but without the deadly genetic machinery. Once introduced into the body, this harmless particle should appear foreign enough for the immune system to attack. The human papillomavirus vaccine takes this approach.

Protein-subunit vaccine

Researchers hope that by injecting synthetically produced S protein into the body with no genetic material attached, they can induce an immune response that would prime the body to attack the coronavirus. If this defense isn't entirely successful, it could still prevent developing serious complications like pneumonia. Some influenza vaccines work this way.

RNA- and DNA-based vaccines

Researchers have sequenced the SARS-CoV-2 genome and are using it to synthesize its RNA. Like many viruses, coronaviruses have RNA instead of DNA, and some scientists use the RNA to create the corresponding DNA. Once the genetic material is injected into the body — without a virus to carry it — it is taken up by cells that begin producing the S protein, triggering an immune response. There is some concern that the vaccine's DNA could subvert the cell's normal function. But DNA has the advantage of being more stable than RNA.