Killed or Live Vaccine, Which One to Choose?

By Acharya Tankeshwar •  Updated: 05/21/22 •  8 min read

Live, attenuated vaccines and inactivated vaccines are two basic types of vaccines used to protect susceptible individuals from infectious diseases.

Live-attenuated vaccines

Live-attenuated vaccines contain live pathogens, either bacteria or viruses that have been “attenuated,” or weakened. Wild viruses or bacteria are attenuated in a laboratory, usually by repeated culturing. For example, a live attenuated measles vaccine was prepared by almost 10 years of serial passage using tissue culture media.

Live-attenuated vaccines are strong enough to trigger the immune response and produce neutralizing antibodies but too weak to cause disease. If caused disease, it is usually much milder and is considered an adverse reaction to the vaccine.

Live attenuated vaccine production and working mechanism (image source: pfizer)

Benefits of Live Vaccines

The immune response to a live, attenuated vaccine is virtually identical to that produced by a natural infection. In general, live vaccines are preferred to killed vaccines because they offer greater and long-lasting protection.

Although live vaccines stimulate a long-lasting response, booster doses are now recommended with measles and polio vaccines.

Examples of Live Vaccines

Limitations of Live Vaccines

  1. Attenuated strains of pathogens may revert to virulent form either during the production of vaccines or in the immunized person. Of the commonly used live vaccines, only a polio vaccine has had problems regarding reversion to wild forms. Such reversions have not yet been seen with measles, mumps, rubella, and varicella vaccines.
  2. Live vaccine should not be given to immunocompromised people or to pregnant women because although attenuated (weakened), it can still be pathogenic in hosts with weakened immunity. Live, attenuated vaccine may cause severe or fatal infections in persons with a weakened immune system (people suffering from leukemia, HIV infection, or ongoing treatment with certain drugs).
  3. Vaccinated individuals excrete live vaccines in the environment. It is a double-edged sword. For example, the spread of the live attenuated poliovirus vaccine through the feces of the immunized individuals can successfully immunize other persons in that particular locality thus aiding in the production of herd immunity but if the virus reverts to wild type, the neurovirulent strain may spread to susceptible person and may cause paralytic polio (a rare event though).
  4. Contamination of the candidate vaccine by another virus during production may create problems.
  5. Live, attenuated vaccines must be stored and handled carefully as they are fragile and can be damaged or destroyed by heat and light.
  6. Circulating antibodies if present in the host (antibodies transferred from mother to child or antibodies due to previous sub-clinical infections or got via transfusion of blood products) can interfere with the replication of the vaccine organism and lead to poor response or no response to the vaccine, also known as vaccine failure.

Note: People who are allergic to eggs (who have shown anaphylactic reactions to eggs) should not get vaccines grown in chick embryos. For example, influenza, measles, mumps, and yellow fever vaccines.

 Inactivated (killed) vaccines

Inactivated or killed vaccines contain “wild viruses or bacteria that have been killed or inactivated with heat or chemicals. Viral vaccines are inactivated with either formaldehyde or beta-propiolactone (BPL). Formaldehyde is used for the inactivation of poliovirus, hepatitis A virus, Japanese encephalitis virus, and tick-borne encephalitis virus whereas BPL is used for the inactivation of Rabies and Influenza virus vaccines.

Inactivated vaccines include whole-cell inactivated vaccines (such as polio, hepatitis A, and rabies vaccine), subunit vaccines (e.g., influenza pneumococcal vaccines), toxoids (e.g., diphtheria and tetanus toxoid), and recombinant vaccines (e.g., hepatitis B, human papillomavirus (HPV) and influenza). Killed vaccines are usually given intramuscularly and multiple doses are required to produce protective immunity. Inactivated vaccines mostly provide humoral immunity with little or no cell-mediated immunity.

Live attenuated vaccine production and working mechanism (image source: Pfizer)

Benefits of Killed Vaccine

Limitations of Killed Vaccine

Examples of Killed Vaccines

  1. Killed Vibrio cholerae vaccine is used in many cholera endemic countries.
  2. Killed polio vaccine also known as IPV or Salk vaccine is the preferred vaccine to prevent poliomyelitis. It contains all three serotypes of the virus responsible for causing poliomyelitis. The current version of the inactivated vaccine is called enhanced polio vaccine, or eIPV. eIPV has a higher seroconversion rate and induces a higher titer of antibody compared to previous IPV.
  3. Killed Yersinia pestis vaccine is indicated for persons at high risk for contracting plague.
  4. Vaccine against typhus contains killed Rickettsia rickettsiae and is used primarily to immunize members of the armed forces.
  5. The vaccine against Q fever contains killed Coxiella burnetii and is used to immunize those who are at high risk of being exposed to animals infected with the organism.

Difference Between Live and Killed Vaccines

CharacteristicLive VaccineKilled Vaccine
Duration of immunityLongerShorter
Effectiveness of protectionGreaterLower
Immunoglobulins producedIgA (if the vaccine is given via the natural route) and IgGIgG
Production of Cell-mediated immunityYesWeakly or none
Interruption of transmission of virulent virusMore effectiveLess effective
Reversion to virulencePossibleNo
Stability at room temperatureLowHigh
Excretion of vaccine strain and transmission to nonimmune contactsPossibleNo

References and further readings

Acharya Tankeshwar

Hello, thank you for visiting my blog. I am Tankeshwar Acharya. Blogging is my passion. As an asst. professor, I am teaching microbiology and immunology to medical and nursing students at PAHS, Nepal. I have been working as a microbiologist at Patan hospital for more than 10 years.

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