Edible Vaccines

By

J.Ravinder Raju

A new approach to

oral immunization

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 .

Mason et al.,1995

Agro Bacterium Mediated Gene transfer

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

Examples of edible vaccines

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

Hippocrates' celebrated proverb becomes reality:

"Let thy food be thy medicine".

Thankyou

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