About Author: Mr.Mahendra G. Pawar* (B.Pharmacy) Ms.Komal  R. Nikam (B.Pharmacy), Mr.Rakesh D.Amrutkar (M.Pharmacy)

Reference ID: PHARMATUTOR-ART-1059

Biotechnologists in recent years have come up with a new concept.This new concept is about edible vaccine. The difference here lies, that crops like “golden rice” provided extra nutrition that naturally didn’t occur in it. But edible vaccines are GM crops that would provide extra added “immunity” from certain diseases.
Edible vaccines are composed of antigenic proteins and do not contain pathogenic genes (because obviously they use attenuated strains). Thus, they have no way of establishing infection and safety is assured.Oral administration is possible , 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,Cheaper (single dose of hepatitis-B vaccine would cost approximately 23 paise), grown locally using standard methods and do not require immense capital investment of pharmaceutical manufacturing facilities, exhibit good genetic stability. Do not require special storage condition. Since syringes and needles are not used chances of infection are also less. 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.

Edible Vaccines have many potential advantages:(21)
Edible plants are very effective as a delivery vehicle for inducing oral immunization.
Adjuvant for immune response is not necessary.
Excellent , feasibility of oral administration compared to injection.
Easy for separation and purification of vaccines from plant materials.
Effective prevention of pathogenic contamination from animal cells.
Convenience and safety in storing and transporting vaccines.
Effective maintenance of vaccine activity by controlling the temperature in plant cultivation.
Easy for mass production system by breeding compared to an animal system.
Possible production of vaccines with low costs.
Reduced need for medical personnel and sterile injection conditions.
Economical to mass produce and transport.
Reduced dependence on foreign supply.
Storage near the site of use.
Heat stable, eliminating the need for refrigeration.
Antigen protection through bioencapsulation.
Subunit vaccine (not attenuated pathogens) means improved safety.

Dosage of vaccines would be variable.
Not convenient for infants.

Producing stable and reliable amounts of vaccines in plants is complicated by the fact that tomatoes and bananas don’t come in standard sizes! There may also be side-effects due to the interaction between the vaccine and the vehicle. People could ingest too much of the vaccine, which could be toxic, or too little, which could lead to disease outbreaks among populations believed to be immune.

Side Effects of Edible Vaccine:(62)
Development of edible vaccines is a possible high-volume, low-cost delivery system for third-world countries to fight against fatal maladies like AIDS, hepatitis and diarrhea. Research by the National Institute of Allergy and Infectious Diseases (NIAID) and the University of Maryland School of Medicine showed no significant side effects in a small study using genetically-engineered potatoes to make toxin of the Escherichia coli, a diarrhea-causing bacterium.

No Serious Side Effects:
Volunteers reported no serious adverse reactions to genetically-altered potatoes used to deliver edible vaccine toxin, according to the National Institutes of Health. The NIH said 10 to 11 volunteers who ate the raw potato bites developed four times the antibodies against the E. coli bacteria without obvious side effects.

Reduced Anaphylactic Risk:
Reduced risk of anaphylactic side effects from edible vaccine over injection systems is one benefit reported by the They report the edible vaccine carries only part of the allergen compared to injection methods that reduce anaphylactic risk.

Possible Disease Spread:
Potential risk of spreading the disease by edible vaccine delivery is a concern of Potential contamination of the oral delivery system is a possible danger.

Delayed Reactions:
Long-term reactions to edible vaccines are yet to be determined. Possible delayed reactions not yet discovered are dangers the World Health Organization would like further study on before edible vaccines are put into production.

The objective of present review article is to provide detailed information on a new dosage form of vaccines i.e. edible vaccines produced from transgenic plants. This review includes the study of edible vaccines, their advantages, and their future prospectus along with some examples.

Edible vaccines hold great promise as a cost-effective, easy-to-administer, easy-to-store, fail-safe and socioculturally readily acceptable vaccine delivery system, especially for the poor developing countries. It involves introduction of selected desired genes into plants and then inducing these altered plants to manufacture the encoded proteins. Introduced as a concept about a decade ago, it has become a reality today. A variety of delivery systems have been developed. Initially thought to be useful only for preventing infectious diseases, it has also found application in prevention of autoimmune diseases, birth control, cancer therapy, etc. Edible vaccines are currently being developed for a number of human and animal diseases. There is growing acceptance of transgenic crops in both industrial and developing countries. Resistance to genetically modified foods may affect the future of edible vaccines. They have passed the major hurdles in the path of an emerging vaccine technology. Various technical obstacles, regulatory and non-scientific challenges, though all seem surmountable, need to be overcome. This review attempts to discuss the current status and future of this new preventive modality.
Vaccines have been revolutionary for the prevention of infectious diseases. Despite worldwide immunization of children against the six devastating diseases, 20% of infants are still left un-immunized; responsible for approximately two million unnecessary deaths every year, especially in the remote and impoverished parts of the globe. This is because of the constraints on vaccine production, distribution and delivery. One hundred percent coverage is desirable, because un-immunized populations in remote areas can spread infections and epidemics in the immunized "safe" areas, which have comparatively low herd immunity. For some infectious diseases, immunizations either do not exist or they are unreliable or very expensive. Immunization through DNA vaccines is an alternative but is an expensive approach, with disappointing immune response hence the search is on for cost-effective, easy-to-administer, easy-to-store, fail-safe and socioculturally readily acceptable vaccines and their delivery systems. As Hippocrates said, "Let thy food be thy medicine," scientists suggest that plants and plant viruses can be genetically engineered to produce vaccines against diseases such as dental caries; and life-threatening infections like diarrhea, AIDS, etc. This is the concept of edible vaccines. The following discussion will address issues relating to their commercial development, especially their usefulness in preventing infectious diseases in developing countries.

Mechanism of Action:(50)
The antigens in transgenic plants are delivered through bio-encapsulation, i.e. the tough outer wall of plant cells, which protects them from gastric secretions and finally break up in the intestines. The antigens are released, taken up by M cells in the intestinal lining that overlie peyer's patches and gut-associated lymphoid tissue (GALT), passed on to macrophages, other antigen-presenting cells; and local lymphocyte populations, generating serum IgG, IgE responses, local IgA response and memory cells, which would promptly neutralize the attack by the real infectious agent.

Preparation of Edible Vaccines:(50)

Fig.1: Preparation of Edible Vaccines

Introduction of foreign DNA into plant's genome can either be done by bombarding embryonic suspension cell cultures using gene-gun or more commonly through Agrobacterium tumefaciens, a naturally occurring soil bacterium, which has the ability to get into plants through some kind of wound (scratch, etc.). It possesses a circular "Ti plasmid" (tumor inducing), which enables it to infect plant cells, integrate into their genome and produce a hollow tumor (crown gall tumor), where it can live. This ability can be exploited to insert foreign DNA into plant genome. But prior to this, the plasmid needs to be disarmed by deleting the genes for auxin and cytokinin synthesis, so that it does not produce tumor. Genes for antibiotic resistance are used to select out the transformed cells and whole plants, which contain the foreign gene; and for expressing the desired product, which can then be regenerated from them.
The DNA integrates randomly into plant genome, resulting in a different antigen expression level for each independent line, so that 50-100 plants are transformed together at a time, from which one can choose the plant expressing the highest levels of antigen and least number of adverse effects. Production of transgenic plants is species dependent and takes 3-9 months. Reducing this time to 6-8 weeks is currently under investigation. Some antigens, like viral capsid proteins, have to self-assemble into VLPs (virus-like particles). VLPs mimic the virus without carrying DNA or RNA and therefore are not infectious. Each single antigen expressed in plants must be tested for its proper assembly and can be verified by animal studies, Western blot; and quantified by enzyme-linked immunosorbentassay (ELISA).
Approaches to mucosal vaccine formulation include (i) gene fusion technology, creating non-toxic derivatives of mucosal adjuvants; (ii) genetically inactivating antigens by deleting an essential gene; (iii) co-expression of antigen and a cytokine, which modulates and controls mucosal immune response; and (iv) genetic material itself, which allows DNA/RNA uptake and its endogenous expression in the host cell. Various mucosal delivery systems include biodegradable micro- and nanoparticles, liposomes, live bacterial/viral vectors and mucosal adjuvants. "Prime-boost" strategy combines different routes of administration and vaccine types, especially where multiple antigens or doses are required. For example, a single parenteral dose of MV-H DNA (measles virus haemagglutinin) followed by multiple oral MV-H boosters could induce greater quantities of MV-neutralizing antibodies than with either vaccine alone.


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