Edible Vaccines

WHAT IS  VACCINE?

• The vaccine is a biological preparation that improves immunity against a particular disease.
• It contains an agent that resembles a disease-causing microorganism and is often made from a weakened or killed form of microbe, its toxins or one of its surface proteins.
• The agent stimulates the body’s immune system to recognize foreign antigen and destroy it.
• Edward Jenner in 1796 used the first vaccine in humans which was against smallpox.

Image Source: Srinivas Bhairy

What is the Edible vaccine?

• The edible vaccine involves the introduction of selected desired genes into plants and then inducing these altered plants to manufacture the altered protein.
• The genes encoding antigens of bacterial and viral pathogens can be expressed in plants in a form in which they retain native immunogenic properties.
• Edible vaccines were initially thought to be useful only for preventing infectious diseases.
• it has also found application in the prevention of autoimmune diseases and cancer therapy.

CONCEPT OF EDIBLE VACCINE

Developed by Arntzen in 1990s

      Introduce genes of interest in plants(transformation)

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      Genes expressed in the plant tissues edible parts(transgenic plants)

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       Genes encode punitively protective vaccine antigens from viral, bacterial and parasitic pathogens that cause disease in humans and animals

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      Ingestion of edible parts of the transgenic plant

                (oral delivery of vaccine)

MECHANISM OF ACTION

• Edible vaccine when taken orally undergoes the mastication process and the majority of plant cell degradation occurs in the intestine as a result of the action of digestive or bacterial enzymes on the edible vaccine.
• Peyer’s patches are an enriched source of IgA producing plasma cells and have the potential to populate mucosal tissue and serve as mucosal immune effector sites.
• The breakdown of edible vaccine near PP, consisting of the 30-40 lymphoid nodules on the outer surface of the intestine and contain follicles
• These follicles act as the site from which antigen penetrates the intestinal epithelium, thereby accumulating antigen within the organized lymphoid structure.
• The antigen then comes in contact with M-cell.
• M-cell passes the antigen to macrophages and B-cell.
• This B-cell activates the T-cell to provide an immune response.

FACTORS AFFECTING EFFICACY OF EDIBLE VACCINES

• Antigen selection.
• Efficacy in the model system.
• Choice of plant species.
• Delivery and dosing issues.
• Safety issues.
• Public perceptions and attitudes to genetic modification.
• Quality control and licensing.

PLANTS USED FOR EDIBLE VACCINE

• Tobacco
• Potato
• Banana
• Tomato
• Rice
• Lettuce
• Soybean
• Alfalfa
• Carrot
• Peanuts
• Wheat
• Corn

Advantages and disadvantages of different plants

Potato 

Advantage

• Easily transformed.
• Easily propagated.
• Stored for long periods without refrigeration.

Disadvantage

• Need cooking which denatures antigen

Banana

Advantages

• Do not need cooking.
• Protein not destroyed even after cooking.
• Inexpensive.
• Grown widely in developing countries.

Disadvantages

• Trees take 2-3 to mature years.
• Spoils rapidly after ripening.

Rice

Advantages

• Commonly used in baby food.
• High expression of the antigen.

Disadvantages

• Grows slowly.
• Requires a glasshouse condition.

Properties of ideal vaccine

• It should be effective and affordable.
• Vaccination should be simple.
• Should not contaminate the environment.
• Long-lasting cellular and humoral immunity.
• Nontoxic or non-pathogenic.
• Very low levels of side effects.
• Do not cause problems in individuals with impaired immune systems.

DEVELOPING AN EDIBLE VACCINE

• There are two ways of developing an edible vaccine.
• In one case, the entire structural gene is inserted into the plant transformation vector between 5’ and 3’: this will allow the transcription and accumulation of encoding sequence in the plant.
• In the second case, epitope within the antigen are identified, DNA fragment encoding these can be used to construct gene by fusion with a coat protein gene from plant virus e.g. TMV or CMV.

CLINICAL TRIAL

Hepatitis B:

• First human trials of a potato-based vaccine against Hepatitis B have reported encouraging results.
• The amount of HBsAg needed for one dose could be achieved in a single potato.
• Levels of specific antibodies significantly exceeded the protective level of 10mIU/mL in human

ADVANTAGES

• Do not require administration by injection.
• Possible production of vaccines by low cost.
• Do not require separation and purification of vaccines from plant materials.
• Activate both mucosal and systemic immunity.
• Necessary syringe and needles not required.
• Economical in mass production and transportation.
• Heat stable, eliminating the need for refrigeration.

DISADVANTAGES

• Development of immunotolerance to vaccine peptide or protein.
• Consistency of dosage from fruit to fruit, plant to plant and generation-to-generation is not similar.
• The stability of the vaccine in fruit is not known.
• Dosage of vaccine would be variable.
• The selection of the best plant is difficult.
• Certain foods like potatoes are not eaten raw and cooking the food might weaken the medicine present in it.
• Not convenient for infants.

LIMITATION

• Transgenic contamination can occur.
• Antibiotic resistance marker genes can spread from genetically modified food to pathogenic bacteria.
• Difficulty in dose maintenance.

CONCLUSION

• The edible plant-derived vaccines may lead to a future of safer and more effective immunization.

Edible Vaccines