Global health calls on an old foe to help fight Ebola

by Charlie Whittaker

Since March this year, at least 5,800 people across the countries of Guinea, Liberia, Nigeria, Senegal and Sierra Leone have contracted Ebola. Of those infected, more than 2,800 have died. As well as being the largest outbreak on record, this particular incident is worrying because of its potential scale- in August, the WHO hoped to have it contained within 9 months (and with 20,000 infected) but recent research by American epidemiologists suggests that the process of containment could take up to 18 months, with 100,000s of people infected before the outbreak is brought under control.

Ebola is the common name for Ebola Haemorrhagic Fever, caused by the similarly named ebolavirus. Spread through direct contact with bodily fluids such as blood or vomit, symptoms tend to manifest after a 1-2 week incubation period. Fever, muscle pain, vomiting and declining organ function are all symptoms, usually followed by significant internal and external bleeding.

The disease has a startlingly high mortality rate; this varies from outbreak to outbreak, but is usually put at somewhere between 50 and 90%. Pressingly, there is currently no available specific treatment for the disease, with care usually limited to oral rehydration therapy and intravenous fluids. This lack of effective treatment coupled with the naturally high mortality rate means any outbreak has the potential to claim many lives, and is therefore a serious concern for both the countries involved and the wider international community.

Recent efforts by the American government have seen an experimental vaccine fast tracked and delivered to 2 infected aid workers without the usual rounds of clinical trials. ZMapp contains neutralising humanised antibodies that recognise and bind specifically to ebolavirus particles, rendering them harmless.

Given the potential scale and immediacy required of doses of vaccine, a problem is presented in terms of the means of production. Many thousands of doses are required, often at very short notice. In order to circumvent this potential issue, researchers have been investigating the potential for the use of plants as “bioreactors” to grow and produce these antibodies.

The principle behind this approach involves the inoculation and subsequent infection of a particular strain of tobacco, Nicotiana benthamiana (a close relative of the cigarette supplying cousin Nicotiana tabaccum) with a virus from the group of plant viruses called the Geminiviridae. These have single stranded circular DNA genomes, and although responsible for significant crop losses worldwide, here they have been co-opted for human benefit.

Nicotiana benthamiana  Image Credit: Charles Andres

Nicotiana benthamiana
Image Credit: Charles Andres

Their genomes are exceedingly pliable, and extra sections of DNA can be inserted in without compromising infectivity. In this case, DNA sections encoding the humanised antibodies making up the ZMapp treatment were inserted, and the subsequent genome produced then transfected into the plant. Once inside the plant, the existing viral features of the genome ensure replication and propagation of the entire vector, including the antibody, leading to production of high levels of antibody. These antibodies can then be purified and extracted from the plant, and refined in order to provide doses of the vaccine.

The advantages of production and accumulation of antibodies from plant-based bioreactors are numerous. Firstly, the particular viruses in question, the Geminiviridae, are able to replicate extensively within the plant, resulting in high yields. In addition, costs of production are lower as the maintenance of growing conditions is relatively inexpensive. Finally, generating the Ebola antibodies in plants minimises the risk of cross contamination with other mammalian viruses.

All in all then, could this be a timely and effective source of the treatment for this deadly disease? ZMapp has been fast-tracked in this instance, but must first still pass a battery of clinical trials to ensure its efficacy and safety, and questions still remain over the accessibility of it as a healthcare option for the poorest worldwide, for whom it is perhaps most urgently needed. Perhaps more solidly impressive is the global attention gained for the use of plants as bioreactors, and for their ability no act as relatively inexpensive and high yielding sources of various pharmaceutical goods. This makes them potentially able to lower the current cost of production to levels that would make these pharmaceutical products more universally affordable.

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