An inactivated vaccine is one that uses a killed virus or bacteria to stimulate the immune system to protect the body against infection. Because the bacteria or virus is dead, it cannot replicate or cause disease.
While inactivated vaccines have the same aims as live vaccines—namely to generate immunity, including antibodies that fight diseases—they may induce a less robust response and often require multiple doses and/or booster shots to achieve adequate protection.
How Do Vaccines Work?
Woman administering a vaccine
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History
Inactivated vaccines were first developed at the end of the 19th century. The practice of variolation (inoculating an uninfected person with pus from an infected person) was commonly used during the 18th century to prevent bacterial infections like smallpox, and it was also sometimes used for preventing diseases during outbreaks, such as typhoid, plague, and cholera.
Scientists in the 19th century learned that isolating the disease-causing pathogen, killing it, and injecting it into the body could still make the body recognize it as harmful, and trigger a disease-specific response. The first inactivated vaccines were developed in the 1880s and the first general-use cholera vaccine in 1896.
Over the generations, scientists have used different methods to kill pathogens being prepared for inactivated vaccines, including heat, chemicals, and radiation.
By the 20th century, chemical inactivation was successfully applied to viruses, in some cases involving the whole pathogen and, in others, only part of the pathogen. It is the latter discovery that led to the development of the subunit vaccine.1
History of Vaccines and Vaccinations
Types of Inactivated Vaccines
There are 85 single and combination vaccines approved for use by the U.S. Food and Drug Administration (FDA).2 Among these are the many inactivated vaccines, also known as whole-killed vaccines, that protect against the following diseases:2
Hepatitis A (given by injection in two doses)
Influenza (given as a flu shot annually)
Japanese encephalitis (given by injection in two doses)
Polio (given by injection in four doses for children and not typically given to adults unless they didn't get it during childhood)
Rabies (given by injection in three doses)
Typhoid (given as a single shot before travel to an endemic region)
Some inactivated vaccines are no longer available in the United States, including those for cholera and plague.
Advantage and Disadvantages
There are pros and cons to every vaccine. In many cases, there is only one version of a vaccine to choose from. Even so, understanding how inactivated vaccines work can help you understand why vaccine doses differ and why some cost more than others.
Vaccine Durability
Vaccine durability refers to the timeframe that a vaccine is effective. Comparatively speaking, the durability of inactivated vaccines tends to fall short when compared to live vaccines.3 This is because the immune system can better recognize a bacteria or virus that actively replicates, even if it doesn't cause disease.
While inactivated vaccines may require up to four doses to achieve the optimal level of protection, live ones generally require one or two.
Examples:
A live vaccine like the measles, mumps, and rubella (MMR) vaccine only requires two doses and delivers what is effectively lifetime protection.4
An inactivated vaccine like the one used for rabies may be needed every six months to two years for those at increased risk of exposure, such as veterinarians, animal control and wildlife officers, and those who work in rabies virus research labs.5
The live oral typhoid vaccine requires repeated doses every five years for people in endemic regions and the inactivated typhoid vaccine delivered by injection requires a repeat dose every two years.6
Subunit Vaccine Durability: While subunit vaccines are technically inactivated, they do not involve the whole pathogen (but rather a fragment of a pathogen) and are considered a distinct category of vaccines. The fragment that's used is chosen for its strong antigenic (immune-stimulating) effect. Subunit vaccines often need booster shots to maintain immune protection.
Storage and Shipping
Because the pathogen in the vaccine is dead, inactivated vaccines have the advantage of being easily stored and shipped, which makes transport easier, especially in parts of the world where resources are limited.
Live vaccines, on the other hand, typically require special shipping and storage requirements. This limitation creates problems in resource-poor areas. These needs can also increase costs and lead to waste due to shorter shelf life.
Storage and shipping have become major topics of concern with the approval of the Moderna and Pfizer COVID-19 vaccines in 2020, both of which require subzero storage temperatures. This limits their distribution to sites that have the facilities to properly store them, slowing the rate of vaccination.
Vaccine Safety
Inactivated vaccines can be given to most people because there is no chance of the dead virus causing disease. With live vaccines, however, there is a small chance that a virus can replicate and cause illness in some people.7
With that said, the only vaccine that is known to have reverted to its pathogenic (disease-causing) form is the live oral polio vaccine, which is no longer used in the United States.8
There is a live vaccine for influenza that is licensed in the United States called FluMist, and the live oral vaccine for polio is not licensed in the US.
Live Vaccine Risk Groups
Organ transplant recipients or anyone taking immunosuppressive drugs, people with HIV, and those undergoing cancer chemotherapy can be at risk of getting an infection from a live vaccine. Not all live vaccines need to be avoided in these situations, but the benefits and risks need to be weighed.8
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