In many developing countries, the number of people covered by vaccination programmes is still too low to secure sufficient protection of the population. The main problem in increasing the coverage is not the availability or the price of vaccines as such, but reaching the people. Therefore, it is doubtful whether edible vaccines will be the ‘magic bullet’ which will solve existing constraints on vaccination.

It is better to prevent a disease than to cure it. The best way to prevent a disease is to have antibodies (be immunized) and the most effective way to get immunized is by vaccination. Vaccinations are by far the most cost-effective health care intervention. According to the World Bank publication ‘Better Health in Africa’, especially vaccination programmes were contributive to reducing the infant mortality rate in Africa from 145 per 1,000 babies under 1 year of age (1970) to 104 (1992). For example, the percentage of vaccinated children under 1 year of age went up from 19 per cent in 1980 to 45 per cent in 1992 for Diphtheria, Tetanus and Pertussis, and from 29 to 61 per cent for tuberculosis (BCG vaccine). In Africa, vaccination coverage has actually reached a level of around 40 to 50 per cent, but has been rising too slowly in recent years. Therefore, alternatives are welcomed to increase this coverage.
Alternative approaches, such as edible vaccines, which aim to increase the vaccination coverage, have to provide clear advantages over the existing ones. Therefore, a new approach has to score better on four criteria for vaccination: it should be (1) available, (2) accessible; (3) acceptable to the ‘consumer’, and (4) effective.

Availability
Especially because of the efforts of UNICEF, availability of vaccines in developing countries is no major problem any more. At the moment, vaccines against Diphtheria, Tetanus, Pertussis, Poliomyelitis, Measles, Tuberculosis, cholera and yellow fever are available in virtually all districts in all countries worldwide. Therefore, edible vaccines are not likely to increase the availability of vaccines.

Accessibility
One might find two types of constraint on accessibility: financial and geographical. Coverage is not limited by financial constraints at the moment, since, from the consumers’ point of view, vaccination programmes are usually free-of-charge. So, if edible vaccines are cheaper, it will be an advantage for donors like UNICEF, but it is not likely to increase coverage. However, it is questionable if a vaccination programme based on edible vaccines will be cheaper, since the cost of such a programme is determined by logistics (the cold chain of refrigerators, etc.), and not by production-costs of the vaccines. Edible vaccines might include logistic advantages since they do not need a cold chain, but might also lead to new logistic problems such as the transport of large volumes of fresh fruit in tropical conditions.
In the case of ‘new’ vaccines produced by recombinant technologies, such as vaccines against malaria, AIDS and hepatitis B, plant vaccines might hold a promise. Production costs of these vaccines tend to be high, and might be a constraint on their inclusion in vaccination campaigns in the future. If plant vaccines could reduce the production costs, they might increase accessibility.
Although vaccines are available at district level, the access of the consumer to these vaccines are often restricted due to distance. Geographical accessibility is the single most important reason why coverage is still below expectations. Edible vaccines could increase geographical accessibility if they are produced at the peripheral level. But this increased accessibility is unlikely to occur if the necessary quality control is only possible at a more central level. Quality control needs advanced technology, of which the availability might even be problematic at national level. At the moment, simple quality control of drugs is often a problem in many countries.

Acceptability
Whether (the form of) a vaccination is acceptable by the consumer, differs per country and even within a country. Acceptability influences the extent to which clients seek contact for vaccinations. The oral rehydration salts, for example, were presented as an important solution to reduce child mortality as it prevents dehydration caused by diarrhoea. But it faced an acceptance problem since it was seen as a drug in various societies. When it appeared not to cure the diarrhoea, people lost confidence.
Cultural meanings are often at stake, using categories which are difficult to deal with by the scientist. For example, whether a particular vaccine will be considered a ‘hot’ or a ‘cold’ subject, determines to a large extent whether or not people will accept it as a possible solution for a particular disease. Besides, every fruit has a certain image because of taste, consistency, shape, or other characteristics. What is considered a positive characteristic by one person, might be considered negative by another. Therefore, it seems important to include cultural acceptability as a selection criteria for suitable plants. This might include the need for more than one plant to distribute one vaccine. It is difficult to predict whether vaccines in tomatoes or bananas will be more or will be less acceptable than ‘conventional’ vaccines.

Effectiveness
The new vaccines are still a long way from proving their effectiveness, that is, producing enough immunity in a child to prevent it from getting the disease. In this respect, testing in animals is of very little significance since many vaccines which have proved to be efficient in animals failed in humans. New vaccines have to be tested worldwide, since their effectiveness is not uniform in different contexts. When the tuberculosis vaccine (BCG) was tested in Wales (UK) and Denmark, it proved to be effective. But recently, it has been shown that it is not effective in the Indian state Madras, probably because tuberculosis is related to corporal defence, and therefore to nutritional status. But even if it will prove to be effective, will it be as effective as existing vaccines? New vaccines are not always an improvement in this respect. For example, the oral polio vaccine, notwithstanding the fact that is includes some clear benefits, has a lower potential than the injected one.
It seems to be difficult to produce vaccine in plants that is stable and constant in quantity and quality. In particular, the quantity of the vaccine in one item might be a problem: one tomato or banana is never the same size as another, while also significant differences in protein content might occur. Therefore the risk of either underdosing (resulting in not having immunized the child) or overdosing (resulting in adverse effects) is real. Also possible side-effects due to interactions between vaccine and vehicle (the fruit) are not known.
Although increasing coverage is the main problem in vaccination campaigns, it only has meaning when the effectiveness and the safety of the vaccine is guaranteed. Edible vaccines still have to prove that they can meet these requirements. It is unacceptable and would adversely affect vaccination programmes if an individual, once  reached by a vaccination programme, receives a vaccine that does not generate immunity to protect him or her from the disease.
Jurrien Toonen

Royal Tropical Institute, Mauritskade 63, 1092 AD Amsterdam, the Netherlands. Fax (+31) 20 568 8444; E-mail Health@KIT.support.nl