DNA Vaccine Outlook
By Sean Henahan, Access Excellence
D.C. (12/1//97) DNA vaccine technology is showing increasing promise
in the treatment of human diseases, and should offer immunizations that
are both safer and cheaper than conventional vaccines, according to a new
consensus report released by the American Academy of Microbiology.
The report, "The Scientific Future of DNA for Immunization" is based
on a colloquium of 25 international experts in microbiology, infectious
diseases and immunology convened in 1996. It suggests that DNA vaccination
may revolutionize the practice of human immunization.
"Recent results obtained from DNA-vaccine testing in animal models suggest
that this new technology may revolutionize the vaccination of humans,"
says Harriet Robinson of Emory University, co-author of the report."Already
we have been able to induce immune responses against diarrhea-causing viruses,
malarial parasites and tuberculosis."
Conventional vaccines have prevented many millions of cases of
killer diseases such as small-pox and polio. But some pathogens, such as
malaria, have proven to be a considerable challenge to vaccine developers.
It is in such cases that DNA vaccines may prove useful. Indeed, a promising
DNA vaccine candidate has been developed for malaria. DNA vaccines are
also currently being developed for over 15 other human illnesses including
AIDS, herpes, tuberculosis and rotavirus, a common cause of childhood diarrhea.
Traditional vaccination methods use either a weakened or killed version
of the disease-causing organism or a component of the organism, such as
inactivated toxins or proteins. These component vaccines can either be
purified from the organism itself or genetically engineered. The
injection or oral administration of these nondisease-causing mimics mobilizes
the immune system to protect the host from the disease.
"Since the first vaccine was developed for smallpox in 1789, the widespread
use of vaccines has resulted in the global eradication of that disease,"
says Dr. Robinson. "We have also eliminated polio and measles from
the United States and drastically reduced the incidence of diptheria, tetanus,
whooping cough, mumps and rubella. Nonetheless, infectious diseases
remain major killers, despite worldwide improvements in sanitation and
DNA vaccination differs from traditional vaccines in that just the DNA
coding for a specific component of a disease-causing organism is injected
into the body. The DNA can be administered either in a saline solution
injected through a hypodermic needle or on DNA-coated gold beads propelled
into the body using gene guns. The actual production of the immunizing
protein takes place in the vaccinated host. This eliminates any risk
of infection associated with some live and attenuated virus vaccines.
The report lists a number of other advantages DNA vaccines have over
classic vaccine methods:
DNA vaccination provides long-lived immune responses, unlike many component
vaccines that require multiple innoculations to maintain immunity.
Vaccines for multiple diseases can all be given in a single inoculation.
Currently, in the United States, the full course of childhood immunizations
requires 18 visits to the doctor or clinic.
All DNA vaccines can be produced using similar techniques. The ability
to use generic production methods greatly simplifies the vaccine development
and production process.
They are extremely stable. Unlike many conventional vaccines that
must be held at a constant temperature, DNA vaccines can be stored under
a vast array of conditions either dried or in a solution. This eliminates
the need for the "cold chain" -- the series of refrigerators required to
maintain a vaccine during distribution. This will greatly improve
the ability to deliver vaccines to remote areas in developing countries.
Candidate vaccines can be recovered from diseased tissue. Microbial DNA
can be isolated from the tissue of an infected animal, purified, amplified
and screened for vaccine candidates.
"It is remarkable that DNA vaccines have come so far since 1992 but
their real contribution is yet to come," says Stephen Johnston of the
University of Texas Southwest Medical Center, a member of the colloquium
steering committee. "In the next few years we will have sequenced
the genomes of most if not all of the worlds pathogens. DNA vaccines
probably offer the best way to translate all that sequence information
into useful vaccines. The marriage of genomics and DNA vaccines may
revolutionize vaccinology as applied to infectious diseases
DNA vaccination may have its own limitations. The most obvious is that
it is limited to developing immune responses against only the protein components
of pathogens. The question of which vector to use also remains controversial.
Moreover, some microbes have an outer shell made of polymerized sugars,
known as polysaccharides. DNA vaccines cannot substitute for the
more traditional polysaccharide-based vaccines, such as the pneumococcal
vaccine for bacterial pneumonia.