New Horizons in Biotechnology
EDIBLE VACCINES ---- A NOVEL APPROACH
Syeda Fakrunnisa Begum*1 and Vidya Godavari K*2
*1
Department of Zoology, K.V.R Govt College (W), KURNOOL, Email: sfag_14@rediffmail.com
*2
Department of Botany, STBC College, KURNOOL, Email : vidyagodavari@gmail.com
Cite this article as:
Syeda Fakrunnisa Begum and Vidya Godavari K (2015). Edible Vaccines - A Novel Approach. In: New Horizons in
Biotechnology. (Eds. Viswanath B and Indravathi G) Paramount Publishing House, India, pp. 298-299.
Majority of the human population is subjected to several infectious diseases. It is necessary to produce new vaccines that have
economic and other advantages over the existing injectable vaccines. Recently plants are being used as the alternative vaccine
production system because of its several advantages over animal system. Edible vaccines hold great promise as a cost-effective,
easy-to-administer, easy-to-store and socio-culturally 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. 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 need to be overcome. The first edible vaccines were
produced in tobacco in 1990 in which 0.02 % recombinant protein of the total soluble leaf proteins was found. Today, several
plants based edible vaccines including potato, banana, carrot, tobacco and maize etc are available that are successfully
engineered by researcher and scientists. For making edible vaccines against the different pathogens, it is necessary to find out
pathogen associated antigenic epitopes or surface antigens. The antigenic epitopes are proteins or peptides that are encoded by
genomic sequences. Among the different epitopes, protective one can be selected for vaccine development that provokes antibody
response. Consequently, edible plant-derived vaccine may lead to a future of safer and more effective immunization. They would
overcome some of the difficulties associated with traditional vaccines, like production, distribution and delivery and they can be
incorporated into the immunization plans. They have passed the major hurdles in the path of an emerging vaccine technology.
However, with limited access to essential health care in much of the world and with the scientific community still struggling with
complex diseases like HIV, malaria, etc, a cost-effective, safe and efficacious delivery system in the form of edible vaccines will
become an essential component in our disease-prevention arsenal.
Keywords: Vaccines, Epitopes, Antigens, Efficacious, Immunization, Recombinant DNA
CONCEPT BEHIND EDIBLE VACCINES:
Edible vaccines are developed by introducing selected
desired genes into plants and introducing these genetically
modified plants to manufacture the encoded proteins. This
process is known as “transformation” and the altered plants
are called as “transgenic plants “. When an antigen of a
pathogen can produce an immunogenic response when
delivered orally, it is considered as a likely unit for an edible
vaccine. The gene encoding the orally active antigenic
protein is isolated from the pathogen and a suitable vehicle
for constitutive or tissue – specific expression of the gene is
prepared. This gene vehicle is then introduced and stably
integrated into the genome of selected plant species and is
then allowed to express to produce the antigen. The
appropriate plant parts containing the antigen are then fed
raw to animals or humans to bring about immunization. This
is obviously more humane and more economical than the
traditional “injection” method generally followed. [1,2]
The selection of a plant system for delivery of edible
vaccines for humans is very important. The desired protein
has to be consumed in its raw and denatured form. So the
edible vaccines can be administered through raw food ie, alfa
alfa for animals and bananas or oranges for human beings.
Several genes encoding antigenic proteins have been
expressed in plants where they are produced in their native
immunogenic form. An effective vaccine for cholera was
developed by the support of WHO. Plants were transformed
with the gene encoding the B subunit of the E coli heat labile
enterotoxin (LT-B). Transgenic potatoes expressing LT-B
were found to induce both serum and secretory anti bodies
when fed to mice; these antibodies were protective in
bacterial toxin assays in vitro. This is the first “proof of
concept” for the edible vaccines. Edible vaccines research is
currently directed at human diseases. This technology is of
immense value for the production of inexpensive vaccines as
feed additives for agricultural animals. Alfa alfa, maize and
heat are the valuable vehicles to deliver vaccines for the
betterment of animal health.
MECHANISM OF ACTION OF EDIBLE VACCINES:
The gene which codes the active antigenic protein is
isolated from the pathogen and is incorporated in a suitable
“gene vehicle”. This gene vehicle is integrated into the
genome of the plant and is allowed to express to produce the
corresponding antigen. Then these plant parts are fed to
animals and humans to run their course. Plant parts are fed
directly since the outer tough wall of plant cells acts to
protect the antigens against attack by enzymes, gastric and
intestinal secretions. This method is known as
bioencapsulation. The plant cell wall breaks in the intestines
to release the antigens. the antigens released are taken up by
M cells in the intestinal lining that are present over the
peyer’s patches (in the ileum)and the gut associated
lymphoid tissue (GALT). Peyer’s patches are the groups of
lymphatic nodules also called aggregated lymphatic follicles.
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New Horizons in Biotechnology
The antigens are then passed on to macrophages and other
APCs (antigen presenting cells) and local lymphocytes .this
triggers formation of serum Ig G, Ig E and local Ig A
antibodies and memory cells. These immediately neutralize
the infectious agents present in the body. [3]
CHALLENGES INVOLVED IN EDIBLE VACCINES:
Human clinical trials have shown that adequate doses
of antigen can be achieved with plant based vaccines[4]. To
determine the right dosage, one must consider the persons
weight , age, fruit/ plant’s size, ripeness and protein content.
The techniques to overcome the limitations are
1. Optimization of coding sequence of bacterial/ viral
genes for expression as plant nuclear genes
2. Expression in plastids
3. Plant viruses expressing foreign genes
4. Coat protein fusions and
5. Viral-assisted expression in transgenic plants
ADVANATAGES OF EDIBLE VACCINES:
A subunit vaccine refers to a pathogen derived protein
that cannot cause disease but can elicit a protective immune
response against the pathogen. Conventional subunit
vaccines as well as edible vaccines are composed of
antigenic proteins and do not contain pathogenic genes .thus
they have no way of establishing infection and safety is
assured. [5,6] However conventional subunit vaccines are
1. Expensive
2. Require very advanced technology
3. Need purification
4. Require refrigeration and are injected through needles
by trained medical workers.
In contrast edible vaccines
1. Enhance conformity especially in children
2. Oral immunization eliminates the need for trained
medical personnel
3. Production is highly efficient
4. They are cheaper and do not require immense capital
investment of pharmaceutical manufacturing facilities
5. Production in large quantities makes us independent
and leads to decrease in foreign supply.
6. They exhibit good genetic stability
7. They are heat stable and do not require cold chain
maintenance
8. Since storage and units will be nearer, long distance
transportation can be avoided.
9. Since syringes and needles are not used, chances of
infection are also less.
10. Fear of contamination with animal viruses is
eliminated because plant viruses do not infect the
humans.
Special advantages are that the administration of edible
vaccines for mothers to immunize the fetus in uterus by
transplacental 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 (esv), etc. [7,8]
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 like banana,
potato, tomato, lettuce, rice etc can also be used involved in
preparing edible vaccines. 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. Edible vaccines show cell mediated
immunity followed by humoral immunity. There are
negligible side effects. [9,10]
CONCLUSION: Edible plant-derived vaccine may lead to a
future of safer and more effective immunization. They would
overcome some of the difficulties associated with traditional
vaccines, like production, distribution and delivery and they
can be incorporated into the immunization plans. They have
passed the major hurdles in the path of an emerging vaccine
technology. Before becoming a reality, the technical
obstacles, though all seem surmountable, need to be
overcome. However, with limited access to essential health
care in much of the world and with the scientific community
still struggling with complex diseases like HIV, malaria, etc,
a cost-effective, safe and efficacious delivery system in the
form of edible vaccines will become an essential component
in our disease-prevention arsenal. Due to various advantages
edible vaccines are definitely going to replace the usual
existing vaccines all through the globe.
REFERENCES
1. http://www.nal.usda.gov/pgdic/probe/v5n1/lead.html
2. http://www.molecular-plant-biotechnology.info/
transgenic-plants-11/ediblevaccines.html
3. Lal P, Ramachandran VG, Goyal R,Sharma R- Edible
vaccines : (2007) Current status and future . Indian
Journal Medical microbiology
4. www.sciencedaily.com
5. www.ijmm.org
6. www.whyfiles.org.
7. Using transgenic plants as bioreactors to produce
edible vaccines .
8. Gunn ,K.S. and Singh, N. and Giambrone,J. and Wu,
H. Journal of Biotech Research(2012) 4(1): 9299[Pubmed]
9. Edible Vaccine: A prospective substitute for better
immunization in future Kesar, R.R. and Kumar, S.and
Nidhi and Kumar,U.International Journal of Pharma
and BioSciences . (2012);3(3):B948-B955{Pubmed]
10. A banana or a syringe: journey to edible vaccines.
Monika Sharma, Bhumika Sood World Journal pf
Microbiology and Biotechnology (2011);27(3):471
11. Promotion of global health through ortal
immunotherapy using edible vaccines Pawar,K. and
Pawar, S.P. and Patel,V.A. and Patel, H.V.
Pharmaceutical Reviews.(2010);8(1) [Pubmed]
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