Chapter 7 Edible Vaccine

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Edible Vaccine: The phrase edible vaccines was first used by Charles Arntzen in 1990 and refers to

any foods; typically plants, that produce vitamins, proteins or other nourishment that act as
a vaccine against a certain disease. Edible vaccines are developed by introducing the selected
desirable genes into the plants and then allowing the production of encoded proteins by these altered
plants (Transgenic plants); the process in termed as transformation.

Some antigens Produced by Edible Plants:

Antigens Plants
CT-B Potato
Foot and mouth virus Arabidopsis
Herpes virus B surface antigen Tobacco
Human cytomegalovirus glycoprotein B Tobacco
Rabies glycoprotein Tomato

Advantages:

 They have better immunization action as they do not require subsidiary elements for
stimulating immune response.
 They cause mucosal immunity.
 They are affordable since they do not require cold chain storage conditions like traditional
vaccines.
 They have greater storage stability since the seeds of transgenic plants can be dried easily due
to their low moisture content.
 They do not require sophisticated equipment and machines, since they can be grown on rich
soils.
 They are acceptable due to their oral administration.
 They impart better opportunity for second-generation vaccines by incorporating many
antigens, which act on M cells at the same time.
 They lack heat-killed pathogens which remove the risk of protein reformation into an
infectious organism, thus are safe.
 Their process of production can be rapidly scaled up by breeding.
Limitations:

 Immune tolerance may develop in the individual for particular vaccine protein or peptide.
 Their dose changes on the basis of generation, plant, protein content, patient’s age and
weight, ripeness of the fruit, and food quantity ingested.
 Their administration requires standardization methods for plant material/product since low
doses produce lower antibodies count and high doses cause immune tolerance.
 They depend on plant stability since some foods cannot be eaten raw and needs to be cooked.
 They are vulnerable to microbial attack.
 A demarcation line should be provided between the vaccine fruit and normal fruit.
 Their functions get disturbed due to the variation in glycosylation pattern of plants and
humans.

Applications:

 Cancer therapy: Monoclonal antibodies made by engineering many plants are verified for
effectiveness in cancer therapy.
 Birth control: Tobacco mosaic virus administration produces a protein present in Mousezona
pellucida. This protein inhibits egg fertilization in mice because of antibodies formed.
 Chloroplast transformation: The chloroplast genome transformation into crops through
usual cross-pollination is not possible, because of its nature of maternal inheritance. But
transmission and accumulation of chloroplast genome in large quantity are possible as
transgenic protein.
 Role in autoimmune diseases: With respect to autoimmune diseases, self-antigen production
in plants and its scale up is under development.
 Recombinant drugs/proteins: Many vaccines and antibodies are produced by recombination
technique.

Example:
 Transgenic potatoes for diarrhoea
 Transgenic tomatoes against diarrhoea.

Production of Vaccine Potatoes:

Genetically modified potatoes are also a viable option and seem to be the desired vector.
Many of the first edible vaccines were synthesized in potato plants. The transgenic potatoes
were developed and grown by Arntzen and Mason and their research group at the Boyce
Thompson Institute for Plant Research, Cornell University. Previously, NIAID supported in
vitro and preclinical studies by John Clements and colleagues at Tulane University School of
Medicine, in which 14 volunteers ate bite-sized pieces of raw potato that had been genetically
engineered to produce part of the toxin secreted by E. coli causing diarrhea. The investigators
periodically collected blood and stool samples from the volunteers to evaluate the vaccine’s
ability to stimulate both systemic and intestinal immune responses. Ten of the 11 volunteers
(91 %) who ingested the transgenic potatoes had fourfold rise in serum antibodies at some
point after immunization, and 6 of the 11 (55 %) also showed fourfold mount in intestinal
antibodies. The potatoes were well tolerated and no one experienced serious adverse side
effects. Vaccine development has successfully tested a potato-based vaccine to combat the
Norwalk Virus, which is spread by contaminated food and water. The virus causes severe
abdominal pain and diarrhea.
A research team led by William Langridge of the Loma Linda University in California has
reported that transgenic potatoes engineered with a cholera antigen, CTB can effectively
immunize mice. Mice fed transgenic potatoes produce cholera-specific antibodies in their
serum and intestine; IgA and IgG antibodies reach their highest levels after the fourth
feeding. In yet another experiment genetically engineered potatoes containing a hepatitis B
vaccine have successfully boosted immunity in their first human trials.
Attempts have also been made to boil the potatoes as raw potatoes are not very appetizing but
unfortunately the cooking process breaks down about 50 % of the proteins in the vaccine.
While some proteins are more tolerant to heat, for most proteins it will be necessary to
amplify the amount of protein in the engineered foods if they are to be cooked before
consumption.
Transformation: The edible vaccines are developed by introducing the selected desired genes which
are incorporated into the selected plants, so that these genetically altered plants (transgenic plants) can
produce encoded proteins, this technique is known as transformation.

Electroporation Method: In this method, the cells are incorporated with DNA. Later high voltage
electrical pulse is applied to these cells, as a result of which transient pores within the plasma lemma
are produced. It also requires a mild enzymatic treatment to weaken the cell wall since it acts as a
barrier for the entry of DNA into the cell cytoplasm.

Plants can make monoclonal


antibodies for cancer
therapy in sufÞ cient quantities.
Soybean has been genetically
engineered to make monoclonal
antibody (BR-96) as a
vehicle for targeting doxorubicin for
breast, ovarian, colon
and lung tumors.3,39 Non-Hodgkin’s
lymphoma is also being
Plants can make monoclonal
antibodies for cancer
therapy in sufÞ cient quantities.
Soybean has been genetically
engineered to make monoclonal
antibody (BR-96) as a
vehicle for targeting doxorubicin for
breast, ovarian, colon
and lung tumors.3,39 Non-Hodgkin’s
lymphoma is also being
Role of Edible Vaccine on Cancer Therapy: Several plants have been successfully engineered to
generate monoclonal antibodies that have been verified as effective cancer therapy agents. One
example is that of monoclonal body in case of soyabean (BR-96) is an efficient agent that attacks
doxorubicin responsible for breast cancer, ovarian cancer, colon cancer and lung tumors.
Plants can make
Role of Edible Vaccines on Cancer Therapy:

monoclonal antibodies for cancer


therapy in sufÞ cient quantities.
Soybean has been genetically
engineered to make monoclonal
antibody (BR-96) as a
vehicle for targeting doxorubicin for
breast, ovarian, colon
and lung tumors.3,39 Non-Hodgkin’s
lymphoma is also being

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