Challenges involved in edible vaccine development

Three successful human clinical trials have shown that adequate doses of antigen can be achieved with plant-based vaccines.
To determine the right dosage, one must consider the person's weight, age; fruit/plant's size, ripeness and protein content. The amount to be eaten is critical, especially in infants, who might spit it, eat a part or eat it all and throw it up later. Too low a dose would fail to induce antibodies and too high a dose would, instead, cause tolerance.
Plants may also get contaminated by foreign proteins which accumulate in low amounts (0.01-2% of total protein) and are less immunogenic; therefore the oral dose exceeds the intranasal/parenteral dose.
For example, oral hepatitis-B dose is 10-100 times the parenteral dose; and 100 gm potato expressing B subunit of labile toxin of ETEC (LT-B) is required in three different doses, to be immunogenic. Attempts at boosting the amount of antigens often lead to stunted growth of plants and reduced fruit formation, as too much m-RNA from the transgene causes gene-silencing(neutralization) in plant genome. (A transgene is genetic material that has been transferred by any genetic engineering technique from one organism to another.).
Some of the techniques to overcome these limitations are
(i) optimization of coding sequence of bacterial/viral genes for expression as plant nuclear genes,
(ii) expression in plastids,
(iii) plant viruses expressing foreign genes,
(iv) coat-protein fusions and
(v) viral-assisted expression in transgenic plants.
Edible vaccines are targeted mostly at developing nations and only small technology companies are investing any research and time in them. The larger companies are more inclined to livestock market than human application. Only few international aid organizations and some national governments are rendering support, but the effort remains largely under-funded.
Also, injectable vaccines against disease such as diphtheria and tetanus are so cheap now that very few are attracted to the possibility of manufacturing edible vaccines for them.

References:
a.Lal P, Ramachandran VG, Goyal R, Sharma R. Edible vaccines: Current status and future. Indian J Med Microbiol [serial online] 2007 [cited 2008 May 2];25:93-102. Available from: http://www.ijmm.org/text.asp?2007/25/2/93/32713
b.Wikipedia