Ian C Ellul

In this editorial I will focus on one of biggest challenges which scientists are facing … vaccines. Actually vaccines represent one of the most successful cost-effective medical advances of all time. Epidemiologically targeted implementation of vaccination programs has diminished both morbidity and mortality from several infectious diseases.

Nowadays recent advances in biotechnology (as well as the understanding of the inductive and effector components of immune responses) are invigorating the whole field of vaccinology. In fact other illnesses are now becoming the new targets in this field, with the dual possibility of marketing either therapeutic vaccines (ex. oncology) or prophylactic vaccines (ex. HPV).

These new advances are basically based on either innovative antigens or the introduction of new adjuvants. We are already seeing several plant-made vaccines being manufactured for veterinary purposes, with current research mainly pursued with four diseases ie avian influenza, Newcastle disease, foot-and-mouth disease and enterotoxigenic Escherichia coli. However it is in this area that researchers are also eyeing what I call ‘virgin platforms’ …. the application of recombinant technology to plants in the field of human medicine.  The former has already brought about major advances in plant biology, allowing production of optimised GM plants. To be truthful, such progression has also meant headaches for key political champions … just a few weeks ago we have seen uproars surrounding the decision of our European Commissioner for Health and Consumer Policy, John Dalli to lift a 13-year ban on the cultivation of a GM potato, called Amflora, to be used for starch by industry.

Nonetheless, new technologies have also enabled the development of noncrop plants (tobacco) to produce pharmaceutical molecules. This approach has major advantages, particularly for the production of pharmaceutical-grade proteins (including glycosylated protein), in terms of speed, costs and safety. And this goes beyond the much advertised US creation of the lycopene-rich genetically modified tomatoes which presumably protect against prostatic cancer, way back in 2002 … and six years later, the Brits also developed the purple tomato, which is also rumoured to reduce cancer risk …. However, an innovative application of plants as bioreactors is their use to express antigenic molecules to be administered as vaccines. Major potential advantages of producing immunogens in plant systems include the possibility of enabling the participation of less developed countries in pharmaceutical production, with an obvious emphasis on addressing local health issues.

Examples of such scientific breakthrough are the recent production in tobacco of a H1N1 2009 vaccine based on the hemagglutinin (HA) protein and the initiation of clinical trials with a recombinant, plant-derived, idiotype vaccine to treat B-cell lymphomas.

In case you are just saying … Well, this is just an editorial for all its worth! … scientists’ Grapevine has it that the next pandemic may quite likely be the Chikungunya virus. The virus, usually transmitted by Aedes aegypti mosquitoes, has now repeatedly been associated with a new vector, Ae. Albopictus (Asian Tiger Mosquito, seen in Malta during the past few weeks). Analysis of full-length viral sequences reveals three independent events of virus exposure to the Asian Tiger Mosquito, each followed by the acquisition of a single adaptive mutation providing selective advantage for transmission by this mosquito. It is extremely rare for this phenomenon, known as evolutionary convergence, to be observed in nature. In virology, convergent mutations have been reported under the extreme selective pressure of antiviral therapy during the treatment of acute (eg neuraminidase mutations of influenza virus) or chronic (eg reverse-transcriptase/protease mutations of HIV) viral diseases. Apparently the selective pressure exerted on Mosquit-transmitted Chikungunya virus through the constraint of having to replicate in a new vector, is similar to that cited for antiviral therapy.

Since the dispersal of the Asian Tiger Mosquito from Asia to Europe is largely the result of human activities (such as the commercial transportation of scrap car tyres), the adaptation of Mosquit-transmitted Chikungunya virus to the Asian Tiger Mosquito provides an incredible demonstration of how viruses can readily circumvent the impact of human interference on the ecosystem. Obviously this means that we are far from immune from future emerging arboviruses that infect humans.