Overview of Inactivated Vaccines

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 antibodies that fight diseases—they tend to induce a less robust response and often need multiple doses and/or booster shots to achieve the same level of protection.

Woman administering a vaccine
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Inactivated vaccines were first developed at the end of the 19th century. While 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, the practice was also used for diseases like typhoid, plague, and cholera.

Scientists in the 19th century learned that by isolating the disease-causing pathogen and killing it, the body would still recognize it as harmful when introduced into the body and trigger a disease-specific response. This lead to the development of the first inactivated vaccines in the 1880s and the first general-use cholera vaccine in 1896.

Over the generations, scientists have used different methods to kill the pathogen, 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.

Types of Inactivated Vaccines

There are 85 single and combination vaccines approved for use by the U.S. Food and Drug Administration (FDA). Among these are a small handful of inactivated vaccines, also known as whole-killed vaccines, that protect against the following diseases:

  • 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 five doses for children and three for adults)
  • 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.

There is also a live vaccine for influenza called FluMist licensed in the United States and a live oral vaccine for polio, which is not.

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, making any comparison moot.

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 duration a vaccine is effective. Comparatively speaking, the durability of inactivated vaccines tend to fall short when compared to live vaccines. This is because the immune system can better "recognize" a bacteria or virus that actively replicate even if it doesn't cause disease.

While inactivated vaccines may require up to five doses to achieve the optimal level of protection, live ones generally require one or two. For instance, a live vaccine like the measles, mumps, and rubella (MMR) vaccine only requires two doses but delivers what is effectively lifetime protection.

By contrast, 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.

The same applies to the oral typhoid vaccine, which requires repeated doses every five years for people in endemic regions. (There is also an inactivated typhoid vaccine delivered by injection that requires a repeat dose every two years.)

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. Their response tend to be more robust than inactivated vaccines because the fragment was chosen because of its strong antigenic (immune-stimulating) effect.

Even so, subunits vaccines often need booster shots to maintain immune protection.

Storage and Shipping

inactivated vaccines have the advantage of being easily stored snd shipped. Because the pathogen in the vaccine is dead, the vaccines generally do not require refrigeration and are ideal for parts of the world where resources are limited.

By contrast, live vaccines typically require special shipping and storage requirements. While this is not a huge problem in the United States, it does create problems in resource-poor areas. This demand can also increase costs and lead to wastage due to shorter shelf life.

Storage and shipping have become a major topic of concern with the approval of the Moderna and Pfizer COVID-19 vaccines in 2020, both of which require subzero storage temperatures. Even in the United States, this limits their distribution to sites that have the facilities to properly store them, slowing the rate of vaccinations.

Vaccine Safety

Inactivated vaccines can be given to most people in that there is no chance of the dead virus causing disease. By contrast, there is a small chance that live vaccines can revert to their original state and cause illness in people who are immunocompromised.

This includes organ transplant recipients on immunosuppressive drugs, people with HIV, and those undergoing cancer chemotherapy. Not all live vaccines need to be avoided, but the benefits and risks need to be weighed before such vaccines are given.

A Word From Verywell

Vaccines are among the greatest achievements of medical science. Irrespective of their type, the benefits—in terms of disease prevention, illness, and death—greatly outweigh the risks.

By contrast, the avoidance of vaccines not only places you or your child at risk but threatens the resurgence of diseases once thought eliminated. Such is the case with measles, a disease declared eliminated in the United States in 2000 that is making a big comeback due in part to anti-vaccination myths and misconceptions.

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