Attenuated virus
Encyclopedia
An attenuated vaccine is a vaccine
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...

 created by reducing the virulence
Virulence
Virulence is by MeSH definition the degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenicity of an organism - its ability to cause disease - is determined by its...

 of a pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...

, but still keeping it viable (or "live"). Attenuation takes an infectious agent and alters it so that it becomes harmless or less virulent. These vaccines contrast to those produced by "killing" the virus (inactivated vaccine
Inactivated vaccine
An inactivated vaccine consists of virus particles which are grown in culture and then killed using a method such as heat or formaldehyde.-Examples:Types include:* viral: polio vaccine and influenza vaccine...

).

Examples

Examples of "live" (i.e. attenuated) vaccines include:
  • Viral: measles vaccine
    Measles vaccine
    Measles vaccine is a highly effective vaccine used against measles. The measles-mumps-rubella-varicella combo vaccine has been available since 2005...

    , mumps vaccine
    Mumps vaccine
    Several varieties of mumps vaccine have been used since 1949, and at least 10 strains were in use in 2006:The first vaccine was a killed mumps virus vaccine developed in 1948 and used in the United States from 1950-1978. This vaccine produced little immune memory, thus had a short duration of...

    , rubella vaccine
    Rubella vaccine
    Rubella vaccine is a vaccine used against rubella.One form is called "Meruvax"....

    , chicken pox vaccine, oral polio vaccine
    Polio vaccine
    Two polio vaccines are used throughout the world to combat poliomyelitis . The first was developed by Jonas Salk and first tested in 1952. Announced to the world by Salk on April 12, 1955, it consists of an injected dose of inactivated poliovirus. An oral vaccine was developed by Albert Sabin...

     (Sabin), yellow fever vaccine
    Yellow fever vaccine
    Yellow fever vaccine is a vaccine used against yellow fever.The vaccine consists of a live, but attenuated, strain of the yellow fever virus called 17D. The 17D vaccine has been used commercially since the 1950s. The mechanisms of attenuation and immunogenicity for the 17D strain are not known...

    , and nasal-spray flu vaccine (including the seasonal flu nasal spray and the 2009 H1N1 flu nasal spray). Rabies vaccine
    Rabies vaccine
    Rabies vaccine is a vaccine used to control rabies. Rabies can be prevented by vaccination, both in humans and other animals.-In animals:Currently, pre-exposure immunization has been used on domesticated and normal non-human populations...

    s are now available in two different attenuated forms, one for use in humans, and one for animal usage.
  • Bacterial: BCG vaccine, typhoid vaccine
    Typhoid vaccine
    Typhoid vaccine is a vaccine used against typhoid fever.There are two effective types:* Ty21a, which is a live vaccine* Vi capsular polysaccharide vaccine, which is a subunit vaccine...


Development

Viruses may be attenuated via passage of the virus through a foreign host
Host (biology)
In biology, a host is an organism that harbors a parasite, or a mutual or commensal symbiont, typically providing nourishment and shelter. In botany, a host plant is one that supplies food resources and substrate for certain insects or other fauna...

, such as:
  • Tissue culture
    Tissue culture
    Tissue culture is the growth of tissues or cells separate from the organism. This is typically facilitated via use of a liquid, semi-solid, or solid growth medium, such as broth or agar...

  • Embryonated eggs
    Egg (biology)
    An egg is an organic vessel in which an embryo first begins to develop. In most birds, reptiles, insects, molluscs, fish, and monotremes, an egg is the zygote, resulting from fertilization of the ovum, which is expelled from the body and permitted to develop outside the body until the developing...

  • Live animals


The initial microorganism population is applied to the foreign host. One or more of these will possess a mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...

 that enables it to infect the new host. These mutations will spread, as the mutations allow the microorganisms to grow well in the new host; the result is a population that is significantly different to the initial population, and thus will not grow well in the original host when it is re-introduced to the original host (hence is "attenuated"). This makes it easier for the host's immune system to eliminate the agent and thus create the immunological memory cells which will likely protect the patient if they are infected with a similar version of the microorganism in "the wild".

Administration

In an attenuated vaccine, live virus particles with very low virulence are administered. They will reproduce, but very slowly. Since they do reproduce and continue to present antigen beyond the initial vaccination, boosters
Booster dose
In medicine, a booster dose is an extra administration of a vaccine after an earlier dose. After initial immunization, a booster injection or booster dose is a re-exposure to the immunizing antigen. It is intended to increase immunity against that antigen back to protective levels after it has been...

 are required less often. These vaccines are produced by growing the virus in tissue cultures that will select for less virulent strains, or by mutagenesis or targeted deletions in genes required for virulence. There is a small risk of reversion to virulence; this risk is smaller in vaccines with deletions. Attenuated vaccines also cannot be used by immunocompromised individuals.

Advantages of attenuated vaccines

  • Activates all phases of the immune system
    Immune system
    An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

     (for instance IgA
    IGA
    Iga or IGA may stand for:-Given name:* a female given name of Polish origin. The name originates from the female given name Jadwiga and stands for gia,or gina in the USA....

     local antibodies are produced)
  • Provides more durable immunity; boosters are required less frequently
  • Low cost
  • Quick immunity
  • Easy to transport/administer (for instance OPV
    Polio vaccine
    Two polio vaccines are used throughout the world to combat poliomyelitis . The first was developed by Jonas Salk and first tested in 1952. Announced to the world by Salk on April 12, 1955, it consists of an injected dose of inactivated poliovirus. An oral vaccine was developed by Albert Sabin...

     for Polio can be taken orally, rather than requiring a sterile injection by a trained healthworker, as the inactivated form IPV does)
  • Initial "spotting" method first discovered by Easan Anand has very few side effects in comparison to injected antibody vaccines (e.g. tetanus)

Disadvantages of attenuated vaccines

  • Secondary mutation can cause a reversion to virulence.
  • Can cause severe complications in immunocompromised
    Immunodeficiency
    Immunodeficiency is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. Immunodeficiency may also decrease cancer immunosurveillance. Most cases of immunodeficiency are acquired but some people are born with defects in their immune system,...

     patients.
  • Can be difficult to transport due to requirement to maintain conditions (e.g. temperature)

External links

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