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During the last 200 years, vaccination has controlled many major diseases and has led
to the eradication of many deadly diseases. Vaccines that are used for human beings are
mainly of three types: live attenuated microorganisms, inactivated whole microorganisms, or
split or subunit preparations. In 1986, the first recombinant subunit vaccine, the hepatitis
B surface antigen vaccine, produced in Saccharomyces
cerevisiae (Valenzuela et al., 1982), was licensed. First generation vaccines are whole-organism vaccines - either live
and weakened or killed forms - (Alarcon et al., 1999), live, attenuated vaccines, such
as smallpox and polio vaccines that are able to induce killer T-cell
(TC or CTL) responses, helper T-cell
(TH) responses, and antibody immunity. However, there is a small risk that
attenuated forms of a pathogen can revert to a dangerous form, and may still be able to cause
disease in immunocompromised people (such as those with AIDS). While killed vaccines do not
have this risk, they cannot generate specific killer T-cell responses, and may not work at
all for some diseases. In order to minimize these risks, the so-called second
generation vaccines were developed. These are subunit vaccines, consisting of defined protein
antigens (such as tetanus or diphtheria toxoid) or recombinant protein components (such as
the hepatitis B surface antigen) able to generate
TH and antibody responses, but not
killer T-cell responses.
DNA vaccines are third generation vaccines, made up of a small, circular piece
of bacterial DNA (called a plasmid) that has been genetically engineered to produce
one or two specific proteins (antigens) from a microorganism. The
DNA vaccine is injected into the cells of the body, where the
`inner machinery' of the host cells `reads' the
DNA and converts it into pathogenic proteins. Because these proteins are recognized
as foreign, they are processed by the host cells and displayed on their surface to alert
the immune system, which then triggers a range of immune responses. These DNA
vaccines were developed from `failed' gene therapy experiments. The first demonstration of
a plasmid-induced immune response was when mice inoculated with a plasmid
expressing human growth hormone elicited
antibodies, instead of altering growth (Tang et
al., 1992). |