Many diseases for which researchers are attempting to develop vaccines are extremely complex. Some, like AIDS and malaria, are still not fully understood and present an enormous challenge. New technologies resulting from scientific advancements in the area of molecular biology are aiding the development of a new generation of vaccines. These preparations involve the introduction of engineered DNA into the body. Animal models are essential to their development because they continue to provide the best ways of identifying promising and safe vaccines before advancing to human trials.

New approaches to vaccines development - genetic immunization

Delivery Vehicles for Recombinant DNA Vaccines
By the early 1990s, scientists had begun to study new approaches to the production of vaccines that differ in structure from traditional ones. The strategy involves genetic engineering, or recombinant DNA technology, which permits scientists to combine a segment of DNA from one organism with the gene(s) of a second organism.

Plasmid Vaccines. Among the most frequently studied vaccines are recombinant plasmids, DNA strands originally derived from a bacterium, which have been altered to carry a gene(s) that directs the production of an immunizing protein (antigen) from another infectious agent. Without causing disease, the DNA is taken up by the body's cells where it directs the synthesis of proteins that elicit an immune response.

Live, Viral Vector Vaccines. A variety of live infectious but non-disease-causing RNA or DNA viruses or bacteria have been engineered to express the proteins of a disease producing organism. The vector enters the body's cells where the proteins are generated and then induce humoral and cellular immune responses.

Scientists have demonstrated that these recombinant vaccines activate the immune systems of rodents and nonhuman primates, eliciting both antibody-type immunity and killer cell-type immunity against a variety of disease-producing organisms. Researchers are currently conducting additional tests in animals to develop ways of enhancing the immune response before moving to the stage of clinical testing. DNA vaccines can be administered intranasally, injected intramuscularly, or delivered by gene gun, an instrument that propels tiny DNA-coated gold beads into the body's cells.

Recombinant vaccines raise hopes that one day they will be accepted for use in humans to prevent AIDS, malaria, hepatitis C, and other infectious agents for which currently available vaccines produce only limited protection or do not exist at all. Recombinant vaccines also extend some hope for the control of cancer. While cancer cells are not foreign, they carry proteins that are different from those of normal cells. Cancer vaccines are aimed at stimulating an immune response against these tumor proteins. At present, vaccines aimed at prolonging the lives of people whose tumors have been surgically removed are being tested in early trials.

The Search for New Vaccines for Old and Emerging Diseases

AIDS. The statistics regarding HIV/AIDS around the world are astonishing. First recognized in 1981, AIDS has since become a pandemic. At this writing, an estimated 20 million people have died of AIDS around the world, and an additional 40 million are infected. It is well accepted that this disease cannot be eliminated without a vaccine. Animal research plays an especially prominent role in evaluating the effectiveness of potential vaccines to prevent or control HIV/AIDS. Nonhuman primates, particularly rhesus monkeys, provide the best models because they can be naturally and experimentally infected with a virus related to HIV. This animal model system provides a counterpart for studying the disease and for exploring novel approaches, including the use of DNA vaccines to combat this deadly and widespread epidemic. Since the first vaccine trial in 1987, researchers have studied many different potential vaccines in human volunteers.

Hepatitis C. This virus is transmitted through exposure to blood and other bodily fluids, often by contact with intraveneous drug users and persons who engage in high risk sexual behavior. Hepatitis C virus (HCV) infections have a high rate of chronicity, causing cirrhosis and liver cancer in the U.S. Almost 4 million Americans are chronically infected with HCV, resulting in up to 10,000 deaths annually. The isolation of the HCV- DNA in 1987 enabled scientists to begin the quest for a vaccine that protects against the long-term complications of the virus. To date, immunization studies using DNA vaccines that encode for HCV envelope proteins have been shown to be effective in the chimpanzee, the only known animal model susceptible to infection.

Malaria. One of the largest public health problems in the world, malaria affects between 300 million and 500 million people claiming two to three million lives annually. Spread by mosquitoes, malaria parasites invade liver cells and red blood cells. Vaccine development has been extremely difficult because the parasite is extremely complex and undergoes various cyclical changes in the mosquito vector and the human host. New candidate vaccine antigens are being discovered as scientists sequence the genome of the parasites at the various stages of its life cycle. At the present time, only certain monkey species can be infected by human malarial parasites. Potential vaccine candidates that have successfully protected these monkeys are now being tested in clinical trials in malaria endemic areas of the world.

Tuberculosis. The current vaccine, called BCG vaccine (Bacillus Calmette-Guerin), is a weakened strain of bovine tuberculosis (TB); however, it is not highly effective. Despite having a vaccine and antibacterial treatment modalities, three million people die from this disease each year. Although significant challenges remain, researchers have successfully protected mice against TB using a newly developed DNA vaccine that encodes for a protein of the organism. The availability of small animal models with pulmonary TB has enabled scientists to screen large numbers of potential vaccine candidates.

Periodontal Disease. Periodontitis or gum disease, which caused by certain oral bacteria affects 80 percent of the world's adults. Symptoms of this disease include pain, swelling, and bleeding of the gums that can lead to tooth loss. Some scientists believe that periodontitis may be an important risk factor for atherosclerosis and heart disease. Attempts to develop a vaccine to prevent or halt the progression of this disease are underway at this time.

Respiratory Disease. Respiratory Syncytial Virus (RSV) causes lower respiratory tract infections that can be life-threatening for infants and the elderly. At present, there is no licensed vaccine and so-called traditional vaccines have proven ineffective. Scientists are attempting to develop a recombinant RSV vaccine that is suitable for intranasal instillation. Tests for determining the safety and level of resistance that can be achieved by the vaccine are being conducted in the chimpanzee, the only animal that develops a respiratory illness similar to humans.

Leprosy. Also known as Hansen's disease, leprosy has been a public health threat for thousands of years. It affects the skin, nerve endings, upper respiratory system, and eyes, causing severe disfigurement. There is a very low incidence of the disease in the United States, but, tragically, it is endemic in 91 countries around the world. Development of a vaccine for leprosy has been slow due to the lack of animal models for the disease. The only established model is the nine-banded armadillo. Many experts believe that the eradication of this disease will be impossible without a vaccine, but only a few laboratories are working on one.

Hookworm Disease. Causing mild diarrhea or cramps in most people, this intestinal parasite can lead to serious health problems, including mental and physical retardation in newborns and children. Infection occurs in tropical and sub-tropical areas and is estimated to infect up to 1/5 of the world's population. The overwhelming scope of this disease continues despite attempts to control the disease through improvements in living conditions. A hookworm vaccine is currently under development using recombinant technology.