DNA Vaccine Outlook

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 vaccination."

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
and cancer."

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.