Edible vaccines are plant-based vaccines that are administered orally. They activate mucosal immunity and have several advantages over traditional injectable vaccines like lower cost, easier administration and storage, and activation of mucosal immunity. Common foods that have been engineered to produce edible vaccines include potatoes, lettuce, tobacco. Studies in humans and animals have shown that edible vaccines against diseases like diarrhea, hepatitis B, and measles can successfully induce immune responses and antibody production after oral administration.

1. EDIBLE VACCINES
(THERAPEUTIC PROTEINS)

2.  Definition of vaccine.
 History of vaccines.
 Types of vaccines.
 Why edible vaccines?
 What are edible vaccines ?
 How they are produced ?
 What are the Advantages of Edible vaccines?
 Foods transformed to edible vaccines
 Functions of edible vaccine.
 Role of edible vaccines in ensuring health, food
and nutrition security.
 Summary.
 Conclusion.
 References.

3. The terms vaccine and vaccination are derived from Variolae vaccinae,
First used by Edward Jenner.
A vaccine is a biological preparation that induces immunity to a
particular disease.
A vaccine typically contains an agent that is made from weakened, killed
form of microbes, its toxins or surface proteins that stimulates the
immune system.
Administration of vaccines is called vaccination.
(Ref: WHO)

4. VARIOLATION
Done by
inserting or
rubbing the
powered
smallpox scabs
over ruptured
skin.
NASAL-
INSUFFLATION
Administered by
blowing powdered
smallpox scabs, up
the nostrils.
FIRST
GENERATION
VACCINE
Edward Jenner -
cow pox vaccine
Vaccination was
done by arm to
arm transfer.
SECOND
GENERATION
VACCINE
Louis Pasteur
developed
vaccines for
cholera, anthrax
etc.
Vaccination was
done through
injections.
EDIBLE
VACCINE
Vaccination
is through
oral intake of
transgenic
foods
10th century 16th century 16th -17th century 18th -20th century 21st century
HISTORY

5. VACCINES
Live / Attenuated
Weakened form of
the pathogens.
Ex: Measles,
Mumps
Killed or Inactivated
Vaccines
Pathogens do not
replicate but are intact.
Ex: Polio,
Hepatitis
Toxoid vaccines
Contain a toxin or
chemical made by
the bacteria or virus
Ex: Diphtheria,
Tetanus
Subunit & Conjugate
Vaccines
Contain part of a target
pathogen to provoke a
response.Ex: Human
papilloma viruses

6.  vaccines are revolutionary for the prevention of diseases and reduction of morbidity
and mortality.
 In spite of worldwide vaccination against dreadful diseases 20% of infants remain un
immunized especially in the under developed areas of the globe (Lal. P et al., 2018).
 This may be due to various constraints associated vaccine production, storage,
transportation and delivery.
 In the scenario of increasing rate of diseases, some dreadful infections do not have
vaccines, it they are they are unreliable, or they are costly.
 These requirements led the researchers to use plants as the factories for synthesizing
vaccines known as edible vaccines.(Sharma. M et al., 2011).
 Dr.Arntzen expressed first plant derived vaccine for hepatitis.
WHY EDIBLE VACCINES ?

7. EDIBLE VACCINES
 A vaccine in which an antigenic protein is engineered into
an edible plant which after ingestion is uncloaked and
recognized by the immune system to create an immune
memory is called as EDIBLE VACCINE.
(REF: Segen's Medical Dictionary)
 This antigenic protein is produced in the plant by introducing desired gene of interest.
 This process of inducing desired gene of interest and altering plant to produce antigenic
proteins is called TRANSFORMATION.
 Transformed plants are called TRANSGENIC PLANTS.

8. GENE
TRANSFER
1. Entire gene is
inserted.
2. Gene
fragment
encoding a
specific epitope
is inserted.
TRANSFERRED
TO PLANT

9. TECHNIQUE:
 A microorganism is used as carrier for the gene of interest that is to be transferred to plants.
 This process of using a vector to transfer a gene or fragment of gene into a plant is
called vector Transformation.
PROCESS
1.Production of recombinant cell.
2.Exposure of plant part to solution
containing the recombinant cell
4. Exposure to antibiotic medium
3. Callus formation and selection.
4. Plant regeneration.
1
2
4 5
3

10. TECHNIQUE:
 In this method a gene gun shoots the adequately processed DNA particles which penetrate
into chloroplast and integrate with its genome.
 Also called as micro projectile bombardment method or biolistic method.
PROCESS
1. DNA particles are coated with gold.
2. Precipitation of DNA micro particles on plate.
3. Bombardment of plate with plant tissue,
4. Penetration of micro particles and release of
exogenous DNA
5. DNA penetrate in to chloroplast and integrate
With genome.
1
2
3
4,5

11. TECHNIQUE:
 A recombinant plant virus is produced that consists of a
combination of the genomes of two viruses and display
biological properties characteristic for both parent viruses.
 These chimeric viruses are produced by
1. Epi coat technology :
Involves the expression of only the foreign protein.
2. Over coat technology :
Allows the plant to produce entire protein.
A.VIRUS B.CHIMERIC VIRUS
PROCESS: Chimeric viruses are produced and plants are
infected with these viruses.

12. TECHNIQUE:
DNA is introduced into cell by exposing them to high voltage electric pulse for specific time
period.
PROCESS:
1. Exposing cells to DNA 2. Application of electric pulse 3. INTEGRATION OF DNA

13. Activates mucosal
immunity
Adjuvant are not
required.
Relatively low cost Easy for mass
production
Safe Administered
easily
Easy for storage Stable
ADVANTAGES OF EDIBLE VACCINES
EDIBLE VACCINES
VACCINES

14. FOODS TRANSFORMED
TO EDIBLE VACCINE
COMMON FOODS OTHERPLAGUE,RABIES
ANTHRAX
DIARHHEA
HEPATITIS
HEPATITIS,DIABETIS
MEASLES
DIARHHEA
HEPATITIS HEPATITIS

15. Grow quickly and can be cultivated broadly
High content of vitamin A may help to boost the immune response
Easy and cost effective propagation.
Easily transformed and can be propagated ‘eyes’
Can be stored for long periods with out refrigeration.
Does not need cooking.
Proteins not destroy even if cooked.
Consumed raw
Grows fast
High yield
ADVANTAGES

16. FUNCTIONS OF EDIBLE VACCINE
1. INDUCES IMMUNITY: Edible vaccines when
orally taken make the organism immunopotent by
 Activating mucosal immunity.
2. Quashes autoimmunity: Intake of edible vaccines
having autoantigens supresses autoimmunity by
switching on “suppressor” cells of the immune system,
which then block the destructive activities of their
cousins.

17. IMMUNE SYSTEM
1. ACTIVATION OF M CELLS
The immune system is as an organ system that is distributed throughout the body to provide host
defence against pathogens wherever these may enter or spread.
MUCOSAL IMMUNE SYSTEM

18. 2. ACTIVATION OF IMMUNE RESPONSE

19. 1.ACTIVATION OF IMMUNITY: MECHANISM

20. IMMUNE REACTION AFTER EDIBLE VACCINATION

21. DIARRHOEA
Entero toxicogenic Escherichia coli, Noro virus are leading cause of diarrhoea in infants and
in the travellers.
After ingestion of the contaminated food or water these micro organisms colonizes the gut
and releases the toxins called ENTEROTOXIN (LT), NORO VIRUS CAPSID PROTEIN.
Enterotoxin has two sub units:
1. LT- A: responsible for metabolic changes that results in diarrhoea.
2. LT- B: binds to cells and initiates the transport of LT-A .
 Oral immunization with LT-B subunits results in appearance of LT-B antibodies there by
preventing action of LT-A sub unit. (Ref: Carol et al., 1998)
 Noro viruses is single capsid protein that can assemble and stimulate immune response.

22. DISEASE STUDY RESULT REFERE
-NCE
DIARRHOEA POPULATION: 14 healthy adults
EXPERIMENTAL DESIGN
 6 member were fed with
100 grams of transgenic potato expressing LT-B.
 5 members were fed with 50
Grams of transgenic potato expressing LT-B
 3 members were fed with 50grams of potato
DOSAGE: 3.7-15.7μg/ gram
DURATION: 3 days i.e. on 0th ,7th ,21st day.
PARAMETERS EVALUATED:
Blood was screened for
1.Antibodies before and at 7,14,21,28,59th day
after first dose
2.Antibody secreting cells on o,7,14,,28 days.
3.Dairy was maintained for 7 days after each
feeding
4.Stool was assayed for IgA on 7, 14, 21, 28,
59th day
 Serum and stool antibodies
 Neutralizing antibody Titers
11 volunteers showed ˃1:100 at some
point.
Geometric mean on 28th day 1: 267
 Anti body secreting cells:
Day 1 : 0
Day 7 :18.4 per 10 6 PBMC
DAY14 : 6.6 per 10 6 PBMC
DAY 28: 9.1 per 10 6 PBMC
 DAILY DAIRY: 2 members fed
with 100g of TP complained of
nausea.
Corel, etal.,
O et al., 1998
4 Times in 91 % volunteers
4 Times in 55% volunteers
These levels remained higher even
after 59 days from the first day.
LT- B: E. coli toxin ; PBMC: Peripheral blood mononuclear cells

23. DIARRHOEA POPULATION:24 healthy adults
EXPERIMENTAL DESIGN
 11 member were fed with 3 doses
of transgenic potato expressing NV
capsid protein on 0th ,7th ,21st day.
 10members were fed with 2 doses
transgenic potato expressing NV
capsid protein on 0th 21st day.
 4 members were fed with 3 doses
of wild potato on 0th, 7th , 21st day.
DOSAGE: 215-751μg per dose
PARAMETERS EVALUATED:
Blood was screened for
1.Antibodies before and at
7,14,21,28,60 days after first dose.
2.Antibody secreting cells on
o,7,14,21,28 days.
Dairy was maintained for 7 days after
each feeding
 Serum antibodies:
19 of 20 volunteers developed IgG
and Ig M antibodies.
 Anti body secreting cells:
95%(19)0f20 volunteers Reported
IgAASC @ 6-280/106 PBMC.
13 out of 19 responses occurred
after first dose.
 Neutralizing antibody Titers
Corel, etal.,
2007
NV: Noro virus; ASC: Antibody secreting cells ; PBMC: Peripheral blood mononuclear cells
TITER VALUE
Before
Immunization
Ig M Ig G
< 1: 15 1:67
After
Immunization
1:100 1:757

24. GASTRO
ENTERITIS
POPULATION: 24 healthy
individuals
EXPERIMENTAL DESIGN
DOSAGE: 150 grams of TP
containing 215–751 mg of NVCP.
PARAMETERS EVALUATED:
1.Antibodies before and at
7,14,21,28,61st day after first dose.
2.Antibody secreting cells on
o,7,14,21,28 and 30th day.
3.Whole stool was collected on days
0, 7, 14, 21, 28, and 61.v
Corel,
etal., et
al 2000.
No . Of
volunteers
Feeding days
10 0th, 7th 21st TP
10 0th, 21st TP, 7th NP
04 7th, 14th , 21st NP
TP: Transgenic potato; NP: normal potato; NVCP: Norwalk virus capsid protein

25.  Hepatitis refers to an inflammatory condition of the liver.
 It’s commonly caused by a viral infection.
 There are 5 types of viral hepatitis namely A,B,C, D, E.
 Among them viral hepatitis is responsible for significant mortality and morbidity
despite the availability of injectable vaccines.
 Hence HBs surface antigen was expressed in plants which activate immune
system.
HEPATITIS-B

26. HEPATITIS POPULATION: 42 healthy adults
EXPERIMENTAL DESIGN
DOSAGE:
100- 110 grams of potato
HBs antigenic protein:8.5μg/gram
potato.
PARAMETERS EVALUATED:
Blood was screened for
1.Antibodies before and at 7,14,21,28,
35, 42, 56, 70 day.
2.Dairy – card: subjects recorded their
responses from the day of feeding till 3
days.
 10 of 17 members showed marked
increase in antibodies when compared to
day 0.
Six members- double the values after first
dosage.
Four members- Four times the values after
first dosage.
 Six members(fed with 2 doses of
(TP)showed 4 fold increase in antibodies on
70th day when compared to day 1.
 Highest titer value obtained among
the 3 doses fed individuals is 4785 mIU/ml.
 Highest titer value obtained among the
2 doses fed individuals is 863 mIU/ml.
 Dairy card record showed that there
were no adverse reaction after intake of
transformed food up to 3 days.
Thanvala,
et., al
2005.No . Of
volunteers
Feeding days
17 0th, 14th 28st TP
16 0th , 28th ,TP 14th ,
NP
9 0th, 14th 28st NP
TP: Transgenic potato; NP: normal potato; HBs :Hepatitis B surface Protein.

27. HEPATITIS POPULATION: 05 healthy individuals
EXPERIMENTAL DESIGN
 3 members were fed with 2 doses
of transgenic lettuce expressing HBs
Antigenic protein 2 times with in 2
months of time.
 2 members were fed with 2 doses
of non transgenic lettuce .
DOSAGE:
200 g first, and within 2 month, 150 g
HBs antigenic protein: 0.1 to 0.5 mg/100
g of fresh tissue.
PARAMETERS EVALUATED:
Blood was screened for
1.Antibodies before and at 2 and 4 week
after the first ingestion, and 2, 4, and 12
week after the second lettuce ingestion.
 2nd and 4th week after the
first ingestion revealed no significant
levels of HBsAg-specific IgG.
 2 weeks after the second feeding,
sera from all three volunteers
showed HBsAg-specific antibody
titers above 3 IU/l.
 sera from two of these
volunteers had an HBsAgspecific
antibody level higher than 10 IU/l,
accepted as a minimum protective
level against HBV.
 HBsAg-specific antibody
levels declined to 1.7 IU/I
 No side effects were observed
upto 20 wk after first ingestion.
 serum IgA were not detected.
Kapusta.,
et al .2018

28. 50μg of MV-H DNA
vaccine.
Intra muscular
1gram of transgenic
tobacco plant extract
On 21st ,28th 35th 42nd
day
50μg of MV-H DNA
vaccine.
Intra muscular
1gram of tobacco
plant extract
On 21st ,28th 35th 42nd
day
10
MICE
5
5
MEASLES
 Measles is a highly contagious viral disease that is responsible for over 8,00,000 deaths every year.
 Vaccination strategies using two different routes of administration or types of vaccines result in
improved immune responses
 IgG was detected in 90% of
the mice immunized with
MV-H DNA
 Average MV-specific IgG
titers increased from 1,215
to 16,038 following MV-H
plant vaccination
 Neutralizing titer increased
to 100
1gram of tobacco
plant extract
On 90st, 97th 104th
111th day
MV-specific IgG was
detected in all mice
immunized with MV-H
DNA.
By day 70, titers had
54% of mice.
MV-specific serum IgG
titers for mice boosted
with MV-H plant extract
titer, 2,813.
Ref: Diane, et al., 2002

29. ANTHRAX Tomato 2 Groups(5 in
each) of mice
1. Experimental
group
2. Control
group
0th , 14th , 28th , and
60th day transgenic
potato (expressing
anthrax antigen @300
µg) was administered
to groups 1
II wild-type tomato
Transgenic tomato plants
Generated an antibody-
mediated immune response
Mean antibody titer was
1600, as measured before
second booster dose
This level of antibody titer
was maintained until the
last record, which was done
at day 59
Aziz et al., 2005
DIARRHOEA/
CHOLERA
Maize 2 groups 5 mice
in each group
Mice were fed with
maize pellets
containing 10µg of
maize-synthesized or
bacterial LT-B on days
0, 3, 7, and 21
Mice were challenged
with 25μg of CT –B
toxin
Serum anti-LT- B IgG
levels were detected on day
13 after 1st immunization.
Experimental group mean
Ig G :5.7mg/ml
Control group: 5.8mg/ml
Mice did not develop
adverse symptoms of
cholera.
Chikwamba etal.,
2002
DISEASE FOOD SUBJECTS EXPERIMENTAL
DESIGN
CONCLUSION REFERENCE

30. RABIES Spinach
leaves
10 Eight-week-
old female
Swiss–Webster
mice
1 g per dose
7 days transgenic leaves and
7 days normal
(4times)
serum IgG and IgA are
two fold higher than
control group.
40% of the mice were
protected against
challenge infection with
a lethal dose(10ml
IMLD50)
of rabies virus.
Modelska et al.,
1998
RABIES tobacco
plants
Eight-week-old
female Swiss–
Webster mice
5 mice in each group
1.Experimental (10 μg/dose)
intraperitoneal injections at
2-week intervals, and serum
samples were collected 12
days after 3rd and 7th
immunizations
2. control
Low levels of serum
antibodies were
detectable after the3rd
dose
14 days after the last
immunization high titers
of rabies-specific
antibodies were detected
Yusibav etal .,
1997
PLAGUE Tomato 6 Female
BALB/c mice
0th
11th
day
3 doses of transgenic tomato
(300μg of F1–V) with 7 days
interval
Final higher dose of 1200μg
IgG1 was detected
in100% of the mice that
were primed
subcutaneously with
bacterial F1–V.
Highest mean Ig G
detected was
Alvarez et al.,
2006
Bacterially produces
Plague vaccine (0.19
mg per dose)

31. 2. SUPPRESSION OF AUTO IMMUNITY: MECHANISM

32.  Type 1 diabetes is metabolic disorder involving the autoimmune destruction of insulin
producing pancreatic beta cells.
 It if often diagnosed by the detection of auto antibodies against insulin, glutamic acid
decarboxylase, tyrosine phosphatase.
 These auto antigens can be produced in the plants and are used to induce oral tolerance
TYPE-1 DIABETES

33. CHOLERA TOXIN B- SUB UNIT HUMAN PROINSULIN(CTB)
PROTECTS AGAINST DEVELOPMENT OF INSULITIS IN NON
OBESE DIABETIC MICE(NOD)
5 week old mice 5 in each
group received
1. Untreated leaf
2. Transgenic leaf
expressing CTB
EXPERIMENTAL DESIGN
DOSAGE: 8mg of tobacco leaf
containing 14μg of CTB.
DURATION :once in a week for
seven weeks
PARAMETERS EVALUATED
1.Histochemistry for insulitis.
2. Preservation of B cells
3.Serum and intestinal antibodies.
4.Blood glucose.
5.Urine glucose.

34. Histo chemistry for insulitis.
Pancreas were collected from 12
week old mice to assess the
degree of infiltration
Insulitis score of CTB treated
group: 2
Insulitis score of control was
group: 4
Preservation of B cells of
pancreas
In Mice group fed with CTB the b
cells were not destroyed due
apoptosis as there was reduced
synthesis of caspase-3.
Serum
Immunoglobulins.
Serum IG g values of
experimental
group:3mg/ml
Serum IG g values of
control group: nearly
1mg/ml
Experimental
group
Control group
Blood glucose 100 -120mg/dl Above 200
mg/dl
Urine glucose <100mg/dl Up to 200mg/dl
Blood and urine blood glucose levels
Continued………
Ruhlmant, etal., 2007

35. IMMUNOGENECITY OF GLUTAMIC ACID DECARBOXYLASE – A HUMAN AUTO ANTIGEN
 Chlamydomonas reinhardtii algae was transformed to produce glutamic acid D
carboxylase(GAD)
The immunogenicity of the algal derived GAD was determined by its:
1.Reactivity with serum of type 1 diabetic mice
2.In vitro Spleen T cell proliferation responses to algal derived GAD
1.Reactivity with serum of type 1 diabetic mice
50μl of algal solution expressing GAD@ 10μg/ml was
added to micro plate
Incubated overnight at 4°C
50 μl of diabetic serum and non diabetic serum was
added
Color was developed and OD was measured.

36. 2. Spleen T cell proliferation responses to algal derived GAD
In this 7 week old diabetic mice spleen cells were stimulated with
a. Algal derived GAD
b. Insect derived GAD
c. Unrelated antigenic protein
Continued………
This shows that:
 Number T cells are increased stating
that GAD acts as autoantigen.
 Proliferation rate with algal GAD is
comparable with insect GAD.
 Unrelated antigenic protein response
is low suggesting T cell proliferation is
specific to GAD.
Bertini, etal., 2018

37. ROLE OF EDIBLE VACCINES IN ENSURING HEALTH, FOOD AND
NUTRITION SECURITY
EDIBLE VACCINE
HEALTH

38.  Plants can be genetically transformed to produce disease specific antigens.
 Plants can be transformed using different methods.
 Tomatoes, carrots, potatoes and maize are some of the foods that are successfully transformed
to produce specific antigen .
 These transgenic plants when consumed activates immune system and produces antigen
specific antibodies.
 Some clinical evidences suggest that these edible vaccines elicit immune responses on par
with other vaccines.
 Plants can also be transformed to produce autoantigens, to manage autoimmune disorders.

39. • Edible vaccines gives an opportunity to manage infectious diseases and autoimmune disorders
with foods.
• This concept needs more scientific research, several factors have yet to be studied like stability of
antigen upon storage and effect of processing etc.,
• Awareness should be created to ensure its acceptance and sustainable usage.
• As nutrition plays an important role in immunity a combined strategy where plants expressing
more nutrients, antigenic proteins can be a future approach to address the viscous cycle of
malnutrition and decreased immunity.

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