Breaking News

Edible Vaccines – Friends Or Foes?

Edible Vaccines – Friends Or Foes?

As Archimedes could attest, inspiration can strike anywhere. Legend has it that the ancient Greek thinker discovered the mathematical laws governing buoyancy in the bathroom while idly watching soap float. And then running, wet and naked, through the streets of Syracuse yelling, “Eureka!” (“I have found it!”). The nature of scientific research may have changed since the third century B.C., but the spirit of observational inquiry that led to Archimedes’s principle is still active.

Vaccinating people with edible plants is a new idea that appears to hold great promise. Current research is focused at mixing viral or bacterial DNA in a formula, which is then inserted into soil bacteria. When a plant takes on the bacteria, therapeutic DNA becomes stitched into the plant’s genetic makeup and as the plant grows, its cells start to produce whatever proteins the new genes are designed to make. When the plant or fruit is eaten, immunization starts, prompting the body to produce the appropriate antibodies.

The development of vaccines has saved millions of lives around the world. Vaccines have accomplished near miracles in the fight against infectious disease. They have consigned smallpox to history and should soon do the same for polio. By the late 1990s an international campaign to immunize all the world’s children against six devastating diseases was reportedly reaching 80 percent of infants (up from about 5 percent in the mid-1970s) and was reducing the annual death toll from those infections by roughly three million. Yet these victories mask tragic gaps in delivery. The 20 percent of infants still missed by the six vaccines-against diphtheria, pertussis (whooping cough), polio, tetanus and tuberculosis-account for about two million unnecessary deaths each year, especially in the remotest and impoverished parts of the globe. Upheavals in many developing nations now threaten to torpedo the advances of the recent past.

Vaccination stands as one of modern medicine’s greatest success stories. Early experiments by Edward Jenner and Louis Pasteur taught physicians they could prevent disease merely by exposing a patient to a weakened or inactivated pathogen. While his protocols violate today’s clinical trials regulations, Dr. Jenner was able to prevent children from getting smallpox – even when he deliberately exposed them to it – after first inoculating them with the pus from cowpox. Though materially different from those developed by Jenner and Pasteur, modern vaccines, still build upon the same fundamental principle: If the immune system is trained to recognize a pathogen prior to infection, the disease can be prevented when the actual pathogen is encountered.

The problem with current vaccination protocols is that what works in the developed world is often much more difficult to deliver in the developing world, or simply too costly to purchase.

Unfortunately, this often means that the people who most need a vaccine cannot get it.

Disease prevention via an edible vaccine, thus, is great news for people around the globe. An oral vaccine incorporated into a plant bypasses the need for sterile syringes, costly refrigeration, or multiple injections. Furthermore, since many of the developing world’s most deadly diseases – cholera, rotavirus, and E. coli infection, to name a few – enter the body through the gastrointestinal tract, a vaccine that is ingested may actually provide the best protection because it mimics the natural route of infection.

Edible vaccines hold great potential, especially in Third World countries where transportation costs; poor refrigeration and needle use complicate vaccine administration. While research is also being conducted with laboratory animals, diabetics may someday benefit from an edible form of insulin. Researchers have developed technologies that permit the introduction of a hybrid gene that produces human insulin in potatoes.

For diabetics, insulin-bearing potatoes may help train the body’s defenses to stop reacting to insulin as if it were a foreign material. Some scientists see greater promise in plants, which are not affected by human diseases and could produce antibodies at costs up to 100 times less than traditional cell fermentation. Several companies are growing crops that have been engineered to produce human antibodies to diseases like malaria. Edible vaccines for other intestinal pathogens are already in the pipeline–for example, potatoes and bananas that might protect against Norwalk virus, a common cause of diarrhea, and potatoes and tomatoes that might protect against hepatitis B.

Edible vaccines activate both mucosal and systemic immunity, as they come in contact with the digestive tract lining, which is not possible with sub-unit vaccines which provide poor mucosal response. This dual effect of edible vaccines provides first-line defense against pathogens invading through mucosa: like Mycobacterium tuberculosis and agents causing diarrhea, pneumonia, STDs, HIV, etc.

Other advantages of edible vaccines include:

A. Administration of edible vaccines to mothers to immunize the fetus-in-uterus by trans-placental transfer of maternal antibodies or the infant through breast milk. Edible vaccines have a potential role in protecting infants against diseases like group-B Streptococcus, respiratory syncytial virus (RSV), etc, which are under investigation.

B. Edible vaccines would also be suitable against neglected/rare diseases like dengue, hookworm, rabies, etc. They may be integrated with other vaccine approaches and multiple antigens may also be delivered.

Various foods under study are banana, potato, tomato, lettuce, rice, etc. Edible vaccines are currently being developed for a number of human and animal diseases, including measles, cholera, foot and mouth disease and hepatitis B, C and E.

C. Their production is highly efficient and can be easily scaled up. For example, hepatitis-B antigen required to vaccinate whole of China annually, could be grown on a 40-acre plot and all babies in the world each year on just 200 acres of land!

D. They are cheaper, sidestepping demands for purification standard methods and do not require immense capital investment of pharmaceutical manufacturing facilities.

E. They exhibit good genetic stability.

F.They are heat-stable and do not require cold-chain maintenance.

G. Since they can be stored near the site of use, long-distance transportation can also be avoided.

H. Since syringes and needles are not used, chances of infection are also less.

I. Fear of contamination with animal viruses – like the mad cow disease, which is a threat in vaccines manufactured from cultured mammalian cells – is eliminated, because plant viruses do not infect humans.

If a vaccine can be expressed in a plant, the plant can then be eaten for the vaccination, and a person wouldn’t have to go to a doctor to have a shot administered. This could benefit third world countries which lack the infrastructure and resources to provide access to doctors. The first test of edible vaccines was performed by expressing a surface protein of Hepatitis B in potatoes which were then fed to mice. The mice developed antibodies to the Hepatitis surface protein, and developed a mucosal immunity to infection by the virus. It is important to note that the antibodies are secreted by the mucosal membranes (lining of nose, mouth, digestive track) which is the site that the virus is likely to invade the body.

Considerations in developing a plant-based vaccine

Antigen selection

– Is the antigen safe and non-pathogenic in all circumstances?

– Can the antigen induce a protective immune response?

– Is the antigen suitable for expression in plants?

Efficacy in model systems

– Does the antigen accumulate in plants in sufficient quantities?

– Is the plant-derived antigen immunogenic?

– Do trial animals develop protective immune responses?

Choice of plant species for vaccine delivery

– Is it able to be eaten raw and unprocessed?

– Is it suitable for infants?

– Can it be widely and easily grown?

– Can it be easily stored? Is it resistant to spoiling?

– Is it amenable to transformation and regeneration?

Delivery and dosing issues

– Are mucosal adjuvants required for a protective response?

– Can a large enough dose be delivered by simply eating the plant?

– How many doses will be required?

Safety issues

– Will vaccination produce oral tolerance?

– What are the health and environmental risks of genetically modified organisms

Public perceptions and attitudes to genetic modification

– Will negative attitudes to genetically modified organisms influence vaccine acceptability?

Quality control and licensing

– Can antigen expression be consistent in crop production?

– Who will control vaccine availability and

The future of edible vaccines:

The future of edible vaccines may be affected by resistance to GM foods, which was reflected when Zambia refused GM maize in food aid from the United States despite the threat of famine. Before endorsing such vaccines for human use, the WHO’s concerns of quality assurance, efficacy and environmental impact need to be addressed. Random insertion of genes can destabilize the genomes of its plant and animal hosts and the effects could ricochet through the neighboring ecosystem. By facilitating horizontal gene transfer/recombination, genetic engineering may contribute to emergence and re-emergence of infectious, drug-resistant diseases, rise of autoimmune diseases, cancers and reactivation of dormant viruses. Bacteria may take up transgenic DNA in food in human gut. Antibiotic resistance marker genes can spread from transgenic food to pathogenic bacteria, making infections very difficult to treat. Minor genetic changes in pathogens can result in dramatic changes in host spectrum and disease-causing potentials and inadvertently plants may become their unintentional reservoirs. There is also the risk of creating altogether new strains of infectious agents, like super viruses. By DNA shuffling, geneticists can create in a matter of minutes in the laboratory, millions of recombinant viruses that have never existed in billions of years of evolution. This may be misused for the intentional creation of bio-weapons.

The ecological and environmental risks of edible vaccines need to be considered. It is still a very crude science and has a long way to go before it will be ready for large-scale testing in people for combating infectious diseases and for autoimmunity. Addressing concerns about the use of GM food, it can not be overstressed, stringent controls on the growth and processing of plant vaccines to ensure that they never enter the food supply. These will include greenhouse segregation of medicinal from food crops to prevent out crossing, and separate storage and processing facilities.

Dr. Rubina Lone

Consultant Clinical Microbiology and Research

SKIMS Medical College, Srinagar


Feedback at: [email protected]