Last week's International Conference on AIDS in Thailand was marked by a report that pointed to a dearth of innovation in HIV vaccine research, both from the manufacturing perspective and in terms of the mechanism of action of clinical candidates.
Now, researchers in Russia have taken the first steps towards developing an edible HIV vaccine - in transgenic tomatoes - that if successful could provide a low-cost vaccine that stimulates a type of immunity largely ignored by the sponsors of HIV vaccine trials.
The scientists, from the Institute for Biological Chemistry and Fundamental Medicine in Novosibirsk, have managed to express a gene coding for two proteins that could form the basis of an HIV vaccine in the tomato. Significantly, they have acheived expression of the protein not only in the leaves of the tomato plant, but also in its fruit.
Last week's report, published by the International AIDS Vaccine Initiative, took issue with the current thrust of HIV vaccine research because just about all the candidates in trials are based on the same hypothesis that the key to a successful strategy is to stimulate cell-mediated immunity.
This means that if the hypothesis proves incorrect - something that will not happen until major trials complete in 2007 - it will be a major setback.
One alternative hypothesis put forward by the IAVI as justifying further story is that of mucosal immunity, in which a vaccine stimulates an immune response locally, in the tissues of mouth or genital tract. The hope is that this type of vaccine could be effective in preventing transmission of HIV.
Delivering a vaccine in an edible fruit such as a tomato would be one means of engendering mucosal immunity.
Meanwhile, another criticism of the IAVI report was that manufacturing and processing has been largely ignored by the sponsors of current vaccine trials, to the extent that a number of candidates are unsuitable for the large-scale production demanded of a widespread vaccination effort.
The tomato could be an ideal solution, according to the researchers. It is easy to cultivate and does not requrie the thermal processing of other transgenic crops, such as potatoes, that would inactivate the delicate HIV antigens. Also, it is a good storage vehicle for ensuring that the protein antigens retain their activity until they can be delivered to the patient, and compliance should be simple. Individuals would simply be asked to eat the tomato!
They used plasmid DNA to introduce the gene sequences coding for the two HIV proteins into the tomato genome, along with a caulifolower mosaic virus that acted as a promoter to improve the yield of the proteins.
This construct was introduced into tomato germ cells and these were cultivated on a nutrient medium. Those plants which grew roots were planted into soil and cultivated in the hothouse till they matured and developed fruit. Further testing revealed that the genetic trait was passed into the leaves, fruit and seeds of the tomato plants, and was detected in the offspring.
However, the fact that the transgene was present in the progeny of the plants could have advantages in terms of production, but could mobilise opposition to the use of plant crops for this type of 'biomanufacturing'.
Last week, a major European effort to explore the use of transgenic plants for protein production attracted criticism from environmental groups, which are worried that the use of crop plants for biomanufacturing could lead to transgene contamination in the food supply.
One solution put forward to this problem is to use non-food crops such as tobacco or alfalfa, while another is to produce transgenic plants that are only sterile males, which should reduce the risk of transgenes cross-contaminating non-GM crops.