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Contents
Introduction
Potential Advantages
Strategies For Production
Candidates for Edible vaccines
Factors Affecting Efficacy of Edible Vaccines
Mode of action of edible vaccines
Recent Developments
Patents on edible vaccine technologies
Limitations of edible vaccines
Future Research
Conclusion
References
Introduction
A Vaccine is a biological preparation that improves
immunity to a particular disease
The 20% of infants still missed by the vaccination &
about two million unnecessary deaths each year .
This is because of the constraints on vaccine “production,
distribution and delivery”.
Their use in many parts of the world is limited because of
the high costs.
Alternative-cost effective, easy administer store, safe and
socio-culturally readily acceptable-Edible Vaccines.
Edible vaccines are antigenic proteins that are genetically engineered into a consumable crop.
Following consumption, the protein is recognized by the immune system and elicit immune response.
The first report of the production of edible vaccine in tobacco, in the form of a patent(1990)-under IPCT
First tested on humans in 1997, when scientists asked volunteers to eat anti-diarrheal transgenic potatoes .
Potential advantages
Cheap and do not require refrigeration
carried safely to rural areas near site of use.
Lack of needles, Require little or no training at all, which
reduces the cost of vaccination programs.
Subunit vaccine (not attenuated hence, safe)
Generation of systemic and mucosal immunity
Elimination of the purification requirement
Ideal for facing bio-weapons .
Strategies for production
1) Expression of foreign antigens in plant via stable
transformation
2) Delivery of vaccine epitopes via plant virus
Ag-mediated transformation, biolistic methods are some of the
common gene transfer techniques used for production of
edible vaccines .
Candidates of Edible Vaccines
Potato was the first major system
to be used for vaccine production
Potatoes
Bananas
Tomatoes
Lettuce
carrots
Rice
Wheat
Corn
Peanuts and
Soybean
Factors affecting efficacy of edible vaccines
1. Adjuvants : Cholera toxin and E.coli enterotoxins (LT) are potent oral antigens also provide adjuvantcity to other antigens
Mucosal adjunts known to enhance the immunogenicity of the orally delivered antigens
2. Delivery vehicles , to retain the immunogenicity of the antigen when processed .
Mode of action of edible vaccines
The goal of oral vaccine is to stimulate both mucosal and humoral immunity against pathogens
Thus, an antigen produced in the edible part of a plant can serve as a vaccine against agents which invade epithelial membranes
Peyer’s patches are enriched sources of IgA producing plasma cells, populate mucosal tissues.
Targeting strategy
Attaching antigens to cells that bind with M cells inintestinal lining
M cells take in materials that enter intestines and pass them down to other cells like antigen-presenting cells.
Macrophages degrade proteins/antigens into fragments and display them on the cell surface.
When T lymphocytes recognize the foreign fragments they trigger the release of antibodies
and help in bigger attack on the cells .
Recent developments in edible vaccines
A humanized monoclonal antibody against glycoprotein B of
herpes simplex virus 2 (HSV-2) has been expressed in
soybean.
A hybrid monoclonal antibody (IgA/G), having constant
regions of IgG and IgA fused, has been used successfully
against human dental caries caused by the bacterium
Streptococcus mutants .
Transgenic tobacco carrying Norwalk virus capsid protein
(NVCP), tested in mice .
Successful expression of antigens for virus G protein in
tomato against Rabies
Successful expression of Ag for rotavirus VP7 in
transgenic potato, mice when fed produced VP7
specific IgG and IgA .
Genetically modified lactic acid bacteria when fed to
mice, developed antibodies for SARS virus.
The use of alfalfa mosaic virus coat protein fusion
vectors to produce HIV and rabies vaccines has been
studied .
PATENTS ON EDIBLE VACCINES
About 16 international companies obtained patents on edible
vaccine technology such as
Prodigene
Ribozyme – pharm
Rubicon-lab
Applied physiologics
University of Yale
University of Texas
Cornell University
Scripps Res.Institute etc…
(Neeraj Mishra et al., 2008)
Limitations
Development of immune tolerance to vaccine peptide or protein.
Consistency of dosage from fruit to fruit and from plant to plant and from generation to generation is not similar.
Selection of best plant in difficult.
Certain foods like potato are not eaten raw and cooking the food might weaken the medicine present in it .
Future Research on Edible Vaccines
Hold great promise in 3rd world countries, where transportation,
needle use, refrigeration complicate vaccination
MSP : merozite surface protein with mucosal adjuvants for malaria
are under study
Measels vaccines in banana
Hepatitis B vaccine
Auto immune diseases :GAD67 (glutamic acid de- carboxylase)
expressed in potato to prevent diabetes
Cholera vaccine in fruits than in potatoes
vaccines against HIV in trials19
Future on Edible Vaccines
More research is being done to:
Determine if one vaccine can help protect against
multiple diseases
Determine what would be a good dose or how
often vaccine would need to be taken
Selection of best targets for vaccine or antibody
production in plants.
If vaccine can cause a negative response instead
of positive
Edible vaccine should first be tested in animals.
(Neeraj Mishra et al., 2008)
Conclusion
The studies completed so far in animals and people have
provided a proof of principle-indicate that the strategy is
feasible.
Novel edible vaccines that are inexpensive , safe, easily
administered and capable of being stored and transported
without refrigeration.
Production of multi- component vaccines such as trivalent
vaccines that provide protection against several pathogens
References
1) Pant, Geetika and WK, Sanjana, International Journal of Current Agricultural Research Vol. 3, No. 5, PP.076-080, May, 2014.
2) Landridge, W. 2000. Edible vaccines. Scientific Am, 283, 66-71. Leben, M., Johansson, S., & Osek, J. 1993. Large–scale production of vibrio cholera toxin B subunit for use in oral vaccines. BioTechnology, 11, 1574-1578.
3) Ajaz Malik, Vashisht, V.K., Rizwan Rashid, Susheel Sharma and Jaskanwal Singh International Journal of Current Research Vol. 33, Issue, 5, pp.018-026, May, 2011
4) Haq, T.A., Mason, H.S., Clement, J.D. et. al. 1995. Oral Immunization with a Recombinant Bacterial Antigen Produced in Transgenic Plants; Science, 268: 714-716. human, Nat Med, 4 (1998) 601-606
5) Farran, L., Sanchez-Serrano, J.J., Medina, J.F., Prieto, J. & Mingo-Castel, A.M. 2002. Targeted expression of human serum albumin to potato tubers.Transgenic Res., 11: 337-346.
6) Neeraj Mishra, Prem N Gupta, Kapil Khatri, Amit K Goyal and Suresh P Vyas*, Edible vaccines: A new approach to oral immunization, Indian Journal of Biotechnology Vol 7, July 2008, pp 283-294
7) Yu J & Langride W H, A plant based multicomponent vaccine protects mice from enteric diseases, Nat Biotechnol, 19 (2001) 548-552
8) Ajaz Malik, Vashisht, V.K., Rizwan Rashid, Susheel Sharma and Jaskanwal Singh International Journal of Current Research Vol. 33, Issue, 5, pp.018-026, May, 2011
9) Ma J K C, Hikmat B Y, Wycoff K, Vine N D, Chargelegue, D et al, Characterization of recombinant plant monoclonal secretory antibodies in preventive immunotherapy Trends Biotechnol., 1995, 13, 388–392
10) Mason H S, Ball J M, Shi J J, Jiang X, Estes M K et al, Expression of Norwalk virus caspid protein in transgenic tobacco and potato and its oral immunogenicity in mice, Proc Natl Acad Sci USA, 93 (1996) 5335-5340
11) Wu Y Z, Li J T, Mou Z R, Fei L, Ni B, et al, Oral immunization with rotavirus VP7 expressed in transgenic potatoes induced high titres of mucosal neutralizing IgA, Virology, 313 (2003) 337-342
12) Yusibev V, Hooper D C, Spitsin S V, Fleysh, N., Kean, R.B et al, Expression implants and immunogenicity of plant virusbasedexperimental rabies vaccine, Vaccine, 20 (25-26) (2002) 3155-3164
13) Swamy Krishna Tripurani, N. S. Reddy and K. R. S. SambasivaRao*, Green revolution vaccines, edible vaccines, African Journal of Biotechnology Vol. 2 (12), pp. 679-683, December 2003
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