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Abstract: Vaccines composed of DNA, when injected
into subjects the cellular machinery of subjects
translates the nucleotide sequences into peptides which
act as antigens. The peptides are presented in the
context of MHC class I molecules, and are therefore
capable of inducing a brisk cellular immune response, in
contrast with traditional vaccines which produce mainly
a humoral immune response. DNA may be transferred into
the cell by retrovirus, vaccinia virus or adenovirus
vectors or by attachment to cationically charged
carriers such as liposomes, calcium salts or dendrimers.
Alternatively, the desired gene may be directly inserted
into a plasmid and the naked DNA simply injected
intramuscularly. Naked plasmid DNA vaccines bypass the
problem of safety and manufacturing issues arising when
viral vectors are used, and also avoid complications or
interference from an immune response directed at the
delivery vector. For all delivery methods, there is the
unproved potential for insertional mutagenesis. There is
also the concern of inducing tolerance rather than
resistance or anti-DNA antibody formation, leading to
autoimmune diseases. There are no DNA vaccines on the
market, nor even any published data showing efficacy in
Man. Human trials are underway testing the safety and
efficacy of DNA vaccines against influenza, malaria,
hepatitis B virus, HIV, herpes simplex virus, colon
cancer and cutaneous T cell lymphoma. While these early
studies have only just begun to provide suggestions of
vaccine efficacy, the concepts brought forth by DNA
vaccines have dramatically changed the way many
investigators in the basic sciences are approaching
their work.
A DNA vaccine contains a nucleotide sequence encoding a
key antigenic determinant from a given pathogen that is
injected into a host, then translated by host cells into
a peptide that is foreign to the host. Therefore, the
protein is capable of inducing an immune response which
confers protection against the given pathogen.
DNA-mediated immunization, colloquially known as DNA
vaccines, represents a radical change in the way that
antigens are delivered; it involves the direct
introduction of a plasmid DNA encoding an antigenic
protein which is then expressed within cells of the
organism. This leads to surprisingly strong immune
responses, involving both the humoral and cellular arms
of the immune system. DNA-mediated immunization to a
single antigen can provide protection against infection
by a pathogen. This approach to immunization will
greatly facilitate studies of immunophysiological
responses to antigens of pathogenic organisms. After the
first report of a DNA vaccine, there has been an
explosion of work on numerous pathogens with the hope of
introducing a new era of immunization against diseases
which have not yielded to conventional vaccine
production techniques. Human trials testing the safety
and efficacy of vaccines against influenza, malaria,
HIV, herpes simplex virus (HSV), colon cancer and
cutaneous T cell lymphoma are underway. In addition,
animal studies are ongoing for many human pathogens,
from coxsackievirus A-16.
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