Many vaccines are susceptible to heat, and degrade when not refrigerated. In developed countries, this is not an issue, but in developing countries, proper storage is hard to find. In addition, needles and qualified personnel are needed to administer injected vaccines. An alternative to injection is to use oral vaccines. These are taken by mouth in liquid or pill form. Of course, the antigen that is delivered orally must not be degraded by digestive enzymes and must still stimulate the immune system. One example is the oral polio vaccine, which contains live attenuated polio virus, whereas the injected polio vaccine contains inactivated virus. The advantage of the oral vaccine is that the attenuated viruses colonize the intestine and stimulate the immune system the same way that the virulent form of polio would. The disadvantage is the possibility that the live attenuated virus may convert back to a virulent form and the recipient would get polio. The estimate for this is 1 virulent dose in 2.5 million. Where polio itself is very rare, this risk is too great. Most children in the United States now receive the inactivated form of polio vaccine.
Another method of creating heat-stable, low-cost vaccines is to express the antigens in plants and then eat the plant. The benefits of edible vaccines include being able to “manufacture” the vaccine in large quantities cheaply. The patient has to eat a certain portion of plant tissue to acquire immunity. Distributing the vaccine in developing countries is easy, and storage is the same as for standard crops. Recent advances in expressing foreign proteins in plants have facilitated the development of edible vaccines. Genetically engineered potatoes containing a hepatitis B vaccine have currently entered human trials. The volunteers ate finely chopped chunks of raw potato expressing a surface protein from hepatitis B. Sixty percent of those who ate the vaccine had more antibodies against hepatitis B. All participants had previously received the traditional vaccine, so the potato vaccine simply boosted immunity. The main drawback of using vaccines in a food source is the possibility of the vaccine vegetables being confused with normal vegetables and used as food.
Instead of food-based vaccines, researchers are now developing heat-stable oral vaccines. Instead of crops like corn and potato, other edible plants are being developed to express the vaccine. One potential plant is Nicotiana benthamiana, a relative of tobacco that is edible, but is not used for food. The plant is easy to make transgenic, and the vaccine antigens are expressed in the leaf tissue. In order to keep the antigens in the leaf tissue, the recombinant protein is produced only in the chloroplast. Because chloroplasts are only inherited maternally, pollen from the transgenic plant does not contain the transgene. (If pollen did contain recombinant genes, it could be carried to fields of normal tobacco and affect the genetics of normal plants.) Once the vaccine-expressing plant has grown, the leafy part is harvested, washed, ground up, and freeze dried. The powder is then loaded into gelatin capsules. This type of vaccine is easy to transport and distribute, the freeze-dried leaves are heat stable, and the pills are easily administered. Of course, the effectiveness and potential side effects need to be assessed through a series of clinical trials.