Edible Vaccines
Today eighty percent of infants are being vaccinated for diphtheria; pertussis (whooping cough), polio, measles, tetanus and tuberculosis (Landrige 2000). This percentage is up from about five percent in the mid-1970s; however, the death toll from these infections is roughly three million annually. Millions still die from infectious diseases for which immunizations are non-existent, unreliable, or too costly. Vaccines all function with the same idea in mind, priming the immune system to swiftly destroy specific disease-causing agents, or pathogens, before the agents can multiply enough to cause symptoms (Landrige 2000). Classically, this priming has been achieved by presenting the immune system with whole viruses or bacteria that have been killed or made too weak to proliferate much (Landrige 2000).
In the early 1990’s Charles J. Arntzen of Texas A&M found a way to solve many of the problems that bar vaccines from reaching all too many children in developing nations (Landrige 2000). Then Arntzen heard of a world health organization call for an inexpensive, oral vaccine that needed no refrigeration. He then visited Bangkok, where he saw a mother soothe a crying baby with a banana and he thought that perhaps food could be genetically engineered to produce vaccines in their edible parts, which could then be eaten when inoculations were needed (Landrige 2000). A genetically engineered food that would produce a vaccine is an amazing breakthrough in the world of immunization; vaccinations would become cheaper and more readily available.
Long before the causes of disease were known and long before the processes of recovery were understood, and interesting thing was observed: if people recovered from a disease, rather than succumbing to it, they appeared to be immune from a second bout with the same illness (Okonek 2001). First the Chinese tried to prevent small pox (a deadly disease characterized by pus-filled blisters) by exposing uninfected individuals to matter from smallpox lesions. This process was known as “variolation,” and took on several different forms. One form consisted of removing pus and fluid from a smallpox lesion and using a needle to place it under the skin of the person to be protected (Okonek 2001). Another method involved peeling scabs from lesions, drying and grinding then to a powder, and letting an uninfected person inhale this powder. The third and final method was involving a small amount of the scab powder with a needle and then using the needle place the powder directly into the individuals veins (Okonek 2001). During this time Lady Mary Wortley Montagu, wife of the British Ambassador to Turkey saw these procedures taking place in China and brought it back to England (Okonek 2001).
In the late 1700s Edward Jenner noticed a relationship between the equine disease known as “grease” and a bovine disease known as “cowpox” (Okonek 2001). Jenner saw that farmers who treated horses with grease lesions often saw the development of cowpox in their cows, also with very similar lesions to those seen in smallpox. However, unlike smallpox, the cowpox blisters eventually disappeared leaving only a little scar at the site of each blister (Okonek 2001). In 1976 Jenner infected a young boy with cowpox in hopes of preventing a subsequent smallpox infection (Okonek 2001). After allowing the boy to fully recover, Jenner then infected him with smallpox by injecting pus from a smallpox lesion directly under his skin. Luckily as Jenner predicted the boy did not contract smallpox (Okonek 2001).
Disease causing organisms have at least two distinct effects on the body (Six 2001). The first effect is that we feel sick, exhibiting symptoms such as fever, nausea, vomiting, diarrhea, rash, and many others. The second is the disease-causing organism induces an immune response in the infected host, thus resulting in the eventual recovery from the disease. As the response increases in strength over time, the infectious agents are slowly reduced in number until symptoms disappear and recovery is complete (Six 2001). The disease causing organisms contain proteins known as antigens, and the resulting immune response is multi-fold and includes the synthesis of proteins called antibodies. These proteins bind to the disease causing organisms and lead to their eventual destruction. Memory cells are produced in an immune response, and these are cells which remain in the blood stream ready to activate and immune response against subsequent infections with the particular disease-causing agent (Six 2001). This response is so rapid that if the host comes in contact with the disease the infection never develops, you are immune from infection (Six 2001).
The antibodies are the key to the vaccination process because they stick to things. Anti bodies (also called immunoglobulins) are the predominate form of immunity induced by most vaccines (How Do Antibodies 2001). The fact that antibodies stick to things alone can disrupt a lot of pathogen’s functions. The process of a virus infecting a cell can be pretty delicate, and having a big blob of protein hanging off the virus can be enough to block this fine tuned procedure. Especially if the antibodies recognize different parts of a virus, that way you can get twenty antibodies covering the surface of the virus which pretty much will prevent it from doing anything (How Do Antibodies 2001). Antibodies also have some more active functions. Like, after they are bound, some of the antibody subtypes become activated. When activated they trigger a series of events in their general area which will result in inflammation, and generally make that area inhospitable to bacteria and some viruses (How Do Antibodies 2001). Antibodies also increase the efficiency of phagocytosis (the procedure by which cells engulf and destroy particles). When a cell bumps into another particle, it needs some kind of signal to tell it whether it should engulf and destroy it or whether it is a useful component of the body. If the particle had an antibody stuck to it, then that cell would take that as a signal to engulf and destroy it (How Do Antibodies 2001). Antibodies do tend to be relatively ineffective if they’re low in concentrations; they are somewhat less effective at clearing an already-established infection. This particularly pertains to viral infections because the virus rapidly enters a cell and is more or less hidden from the antibody; this is less true for a bacterial infection because bacteria are more likely to hang out outside a cell (How Do Antibodies 2001). Does this mean that antibodies are useless in the case of a viral infection? No necessarily! Many viruses must enter the humoral space (those fluids which are outside the cells of the body) when they leave one cell and enter the next, then they are vulnerable to antibodies. All viruses must be present in the humoral space at one point: when they first enter the body, and it is at this time that the virus is most vulnerable. The virus hasn’t yet had time to replicate, so there are fewer particles there. This is why antibodies (even if they aren’t effective at clearing an already established infection) can be extremely effective at preventing an infection (How Do Antibodies 2001).
Here is a run down of a vaccination process:
1. The vaccine is given by a shot or liquid by mouth. Most vaccines contain a weak or dead disease germ (How Do Vaccines 2001).
2. The body makes antibodies to fight the weak or dead germs in the vaccine (How Do Vaccines 2001).
3. These antibodies practice on the weak germs, so when the real disease germs come the antibodies will know how to destroy them (How Do Vaccines 2001).
4. Protective antibodies stay on guard in the body to safeguard it from the real disease germs (How Do Vaccines 2001).






Many pathogens enter the body through the nose, mouth, or other openings (Landrige 2000). Hence, the first defenses they encounter are those in the mucous membranes that line the airways, the digestive tract and the reproductive tract; these membranes constitute the biggest pathogen-deterring surface in the body. When the mucosal immune response if effective, it generates molecules know as secretory antibodies that dash into cavities of those pathways to neutralize any pathogens they find (Landrige 2000). Injected vaccines initially bypass mucous membranes and typically do a poor job of stimulating mucosal immune responses. However, edible vaccines come in contact with the lining of the digestive tract. In theory, then they would activate both mucosal and systemic immunity (Landrige 2000). That dual effect should help improve protection against many dangerous microorganisms.
Classic vaccines pose a small, but troubling, risk that the vaccine microorganisms will somehow spring back to life, and cause the diseases that they were meant to prevent (Landrige 2000). It is for this reason that subunit vaccines are used. A subuint vaccine is composed primarily of antigenic proteins divorced from a pathogen’s genes (Landrige 2000). These proteins have no way of establishing an infection on their own. However, subunit vaccines are very expensive, and food vaccines are like subunit vaccines in that they are engineered to contain antigens, but bear no genes that would enable whole pathogens to form (Landrige 2000).
Food vaccines are going to place a high priority on combating diarrhea (Landrige 2000). The main causes of diarrhea are Norwalk virus, rotavirus, Vibrio Chloerae (the cause of cholera) and enterotoxigenic Escherichia coli (a toxin-producing source of “traveler’s diarrhea”). These diseases account for some three million infant deaths a year, however mainly in developing nations (Landrige 2000).
In 1995 Arntzen and his researchers had introduced into tobacco plants the gene for a protein derived from the hepatitis B virus, and had gotten the plants to synthesize the protein (Landrige 2000). They then injected the antigen into mice, and it activated the same immune system components that are activated by the virus itself. However injection is not the aim, feeding is. In the past five years experiments conducted by Arntzen and his group at the Boyce Thomson Institute for Plant Research at Cornell University, and the group at Loma Linda University have demonstrated that tomato or potato plants can synthesize antigens from the Norwalk virus, enterotoxigenic E. coli, V. coli, and the hepatitis B virus (Landrige 2000). Also, feeding antigen-laced tubers or fruits to test animals can evoke mucosal and systemic immune responses that fully or partly protect animals from subsequent exposure to the real pathogens or to microbial toxins. Edible vaccines have also provided lab animals with some protection against the rabies virus, Helicobacter pylori (a bacterial cause of ulcers) and the mink enteric virus (which does not affect humans) (Landrige 2000).
The way the edible vaccine provides protection is in the way the digestive tract takes up the vaccine (Landrige 2000). It is the rough outer wall of plant cells that serves as temporary armor for the antigens, keeping them relatively safe from gastric secretions. When the wall finally begins to break up in the intestines, the cells gradually release their antigenic cargo (Landrige 2000). An antigen in the food vaccine gets taken up by M cells in the intestine, and passed to various immune-system cells, which then launch a defensive attack (Landrige 2000)
One way of generating edible vaccines relies on the bacterium Agrobacteruim tumefaciens to deliver into plant cells the genetic blue prints for viral or bacterial antigens (Landrige 2000).
















The key to edible vaccination is the question of whether or not they can be useful in humans (Landrige 2000). Nevertheless, Arntzen and his collaborators obtained reassuring results in the first published human trial, of a dozen subjects who ate raw potatoes containing E. coli. Arntzen has also seen immune reactivity in nineteen of twenty people who ate a potato vaccine aimed at the Norwalk virus. Also Hilary Koprowski has fed transgeic lettuce carrying a hepatitis B antigen to three volunteers, and two of the subjects displayed a good systemic response (Landrige 2000). If research continues to provide results like the few just mentioned, the edible vaccine would be the next biggest thing since sliced bread to third world countries. Not only would these foods provide vaccination, but the would also provide nourishment, they would be relatively inexpensive, and easy to obtain!

















 
 
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    Luckily Jenner | Linda University | Texas A&M | | Edward Jenner | Vibrio Chloerae | Hilary Koprowski | Nevertheless Arntzen | landrige 2000 | okonek 2001 | Ambassador Turkey | antibodies 2001 | 2001 antibodies | England Okonek | immune response | antibodies 2001 antibodies | six 2001 | vaccines 2001 | edible vaccines | immune system | digestive tract | disease causing organisms | landrige 2000 injected | nations landrige 2000 | developing nations landrige |  
   
 
 
 
 
   
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