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An inactivated vaccine (or killed vaccine) is a
vaccine A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified.
consisting of
virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsk ...
particles,
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...
, or other
pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a g ...
s that have been grown in
culture Culture () is an umbrella term which encompasses the social behavior, institutions, and norms found in human societies, as well as the knowledge, beliefs, arts, laws, customs, capabilities, and habits of the individuals in these groups ...
and then killed to destroy disease-producing capacity. In contrast, live vaccines use pathogens that are still alive (but are almost always attenuated, that is, weakened). Pathogens for inactivated vaccines are grown under controlled conditions and are killed as a means to reduce infectivity and thus prevent
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...
from the vaccine. Inactivated vaccines were first developed in the late 1800s and early 1900s for
cholera Cholera is an infection of the small intestine by some strains of the bacterium '' Vibrio cholerae''. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea that lasts a few days. Vomiting an ...
,
plague Plague or The Plague may refer to: Agriculture, fauna, and medicine *Plague (disease), a disease caused by ''Yersinia pestis'' * An epidemic of infectious disease (medical or agricultural) * A pandemic caused by such a disease * A swarm of pes ...
, and
typhoid Typhoid fever, also known as typhoid, is a disease caused by ''Salmonella'' serotype Typhi bacteria. Symptoms vary from mild to severe, and usually begin six to 30 days after exposure. Often there is a gradual onset of a high fever over several d ...
. Today, inactivated vaccines exist for many pathogens, including
influenza Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptom ...
,
polio Poliomyelitis, commonly shortened to polio, is an infectious disease caused by the poliovirus. Approximately 70% of cases are asymptomatic; mild symptoms which can occur include sore throat and fever; in a proportion of cases more severe sy ...
(IPV),
rabies Rabies is a viral disease that causes encephalitis in humans and other mammals. Early symptoms can include fever and tingling at the site of exposure. These symptoms are followed by one or more of the following symptoms: nausea, vomiting, ...
,
hepatitis A Hepatitis A is an infectious disease of the liver caused by ''Hepatovirus A'' (HAV); it is a type of viral hepatitis. Many cases have few or no symptoms, especially in the young. The time between infection and symptoms, in those who develop the ...
and pertussis. Because inactivated pathogens tend to produce a weaker response by the immune system than live pathogens,
immunologic adjuvant In immunology, an adjuvant is a substance that increases or modulates the immune response to a vaccine. The word "adjuvant" comes from the Latin word ''adiuvare'', meaning to help or aid. "An immunologic adjuvant is defined as any substance tha ...
s and multiple " booster" injections may be required in some vaccines to provide an effective immune response against the pathogen. Attenuated vaccines are often preferable for generally healthy people because a single dose is often safe and very effective. However, some people cannot take attenuated vaccines because the pathogen poses too much risk for them (for example,
elderly people Old age refers to ages nearing or surpassing the life expectancy of human beings, and is thus the end of the human life cycle. Terms and euphemisms for people at this age include old people, the elderly (worldwide usage), OAPs (British usage ...
or people with
immunodeficiency Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
). For those patients, an inactivated vaccine can provide protection.


Mechanism

The pathogen particles are destroyed and cannot divide, but the pathogens maintain some of their integrity to be recognized by the immune system and evoke an adaptive immune response. When manufactured correctly, the vaccine is not infectious, but improper inactivation can result in intact and infectious particles. When a vaccine is administered, the
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respon ...
will be taken up by an
antigen-presenting cell An antigen-presenting cell (APC) or accessory cell is a cell that displays antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes usi ...
(APC) and transported to a draining lymph node in vaccinated people. The APC will place a piece of the antigen, an epitope, on its surface along with a major histocompatibility complex (MHC) molecule. It can now interact with and activate T cells. The resulting helper T cells will then stimulate an antibody-mediated or
cell-mediated Cell-mediated immunity or cellular immunity is an immune response that does not involve antibodies. Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines i ...
immune response and develop an antigen-specific adaptive response. This process creates an
immunological memory Immunological memory is the ability of the immune system to quickly and specifically recognize an antigen that the body has previously encountered and initiate a corresponding immune response. Generally, these are secondary, tertiary and other subs ...
against the specific pathogen and allows the immune system to respond more effectively and rapidly after subsequent encounters with that pathogen. Inactivated vaccines tend to produce an immune response that is primarily antibody-mediated. However, deliberate adjuvant selection allows inactivated vaccines to stimulate a more robust cell-mediated immune response.


Types

''Inactivated vaccines'' often refer to ''non-live vaccines.'' They are further classified depending on the method used to inactivate the pathogen: * ''Whole pathogen inactivated vaccines'' are produced when an entire pathogen is 'killed' using heat, chemicals, or radiation, although only
formaldehyde Formaldehyde ( , ) ( systematic name methanal) is a naturally occurring organic compound with the formula and structure . The pure compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde (refer to section ...
and
beta-Propiolactone β-Propiolactone is an organic compound of the lactone family, with a four-membered ring. It is a colorless liquid with a slightly sweet odor, highly soluble in water and miscible with ethanol, acetone, diethyl ether and chloroform.''Merck Index ...
exposure are widely used in human vaccines. * ''
Subunit vaccine A subunit vaccine is a vaccine that contains purified parts of the pathogen that are antigenic, or necessary to elicit a protective immune response. A "subunit" vaccine doesn't contain the whole pathogen, unlike live attenuated or inactivated ...
s'' are produced by purifying out the
antigens In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
that best stimulate the
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
to mount a response to the pathogen, while removing other components necessary for the pathogen to replicate or survive or that can cause adverse reactions. *''Split virus vaccines'' are produced by using a detergent to disrupt the
viral envelope A viral envelope is the outermost layer of many types of viruses. It protects the genetic material in their life cycle when traveling between host cells. Not all viruses have envelopes. Numerous human pathogenic viruses in circulation are encase ...
. This technique is used in the development of many
influenza vaccines Influenza vaccines, also known as flu shots, are vaccines that protect against infection by influenza viruses. New versions of the vaccines are developed twice a year, as the influenza virus rapidly changes. While their effectiveness varies fro ...
. * '' Toxoid vaccines'' are created by inactivating
toxins A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849� ...
produced by bacteria. The toxoid mounts an immune response against the toxin.


Examples

Types include: * Viral: ** Injected
polio vaccine Polio vaccines are vaccines used to prevent poliomyelitis (polio). Two types are used: an inactivated poliovirus given by injection (IPV) and a weakened poliovirus given by mouth (OPV). The World Health Organization (WHO) recommends all chi ...
(
Salk vaccine Polio vaccines are vaccines used to prevent poliomyelitis (polio). Two types are used: an inactivated poliovirus given by injection (IPV) and a weakened poliovirus given by mouth (OPV). The World Health Organization (WHO) recommends all child ...
) ** Hepatitis A vaccine ** Rabies vaccine ** Most
influenza vaccines Influenza vaccines, also known as flu shots, are vaccines that protect against infection by influenza viruses. New versions of the vaccines are developed twice a year, as the influenza virus rapidly changes. While their effectiveness varies fro ...
** Tick-borne encephalitis vaccine ** Some
COVID-19 vaccine A COVID19 vaccine is a vaccine intended to provide acquired immunity against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), the virus that causes coronavirus disease 2019 (COVID19). Prior to the COVID19 pandemic, an e ...
s: CoronaVac,
Covaxin Covaxin (codenamed as BBV152) is a whole inactivated virus-based COVID-19 vaccine developed by Bharat Biotech in collaboration with the Indian Council of Medical Research - National Institute of Virology. As of October 2021, 110.6 million ...
, QazVac, Sinopharm BIBP, Sinopharm WIBP, TURKOVAC, CoviVac * Bacterial: ** Injected typhoid vaccine **
Cholera vaccine Cholera vaccines are vaccines that are effective at preventing cholera. For the first six months after vaccination they provide about 85percent protection, which decreases to 50percent or 62percent during the first year. After two years the level ...
** Plague vaccine ** Pertussis vaccine


Advantages and disadvantages


Advantages

* Inactivated pathogens are more stable than live pathogens. Increased stability facilitates the storage and transport of inactivated vaccines. * Unlike live attenuated vaccines, inactivated vaccines cannot revert to a virulent form and cause disease. For example, there have been rare instances of the live attenuated form of poliovirus present in the oral
polio vaccine Polio vaccines are vaccines used to prevent poliomyelitis (polio). Two types are used: an inactivated poliovirus given by injection (IPV) and a weakened poliovirus given by mouth (OPV). The World Health Organization (WHO) recommends all chi ...
(OPV) becoming virulent, leading to the inactivated polio vaccine (IPV) replacing OPV in many countries with controlled wild-type polio transmission. *Unlike live attenuated vaccines, inactivated vaccines do not replicate and are not contraindicated for
immunocompromised Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
individuals.


Disadvantages

*Inactivated vaccines have a reduced ability to produce a robust immune response for long-lasting immunity when compared to live attenuated vaccines. Adjuvants and boosters are often required to produce and maintain protective immunity. * Pathogens must be cultured and inactivated for the creation of killed whole-organism vaccines. This process slows down vaccine production when compared to genetic vaccines.


References

{{Vaccines