Scientists at UCT are using genetically altered tobacco plants to create vaccines against cervical cancer. They aim to create vaccines that fight the virus not the wallet. Read how.
Rows of bright green, leafy tobacco plants grow in a humid greenhouse. They look identical but one row is special. These are genetically altered tobacco plants, carrying the shell of the human papilloma virus which causes cervical cancer in women.
Tobacco leaves, dried, rolled and smoked, cause lung cancer. But these genetically modified tobacco leaves are little factories, producing a potentially inexpensive vaccine against cervical cancer, the biggest cancer killer of women in Southern Africa and one which is particularly difficult to catch early as it is buried deep within the female reproductive system.
The tobacco plant is an ideal crop for genetic modification. For a start, the genetic alteration doesn’t confer any survival advantage over plants that have not been tweaked. In addition, tobacco and humans have been around each other for so long that they have developed a reliance on each other: the plant can’t escape and grow wild. Just like maize, tobacco requires human intervention to survive in Africa.
"Tobacco is a really well understood crop," says Professor Ed Rybicki of the University of Cape Town. "All of the kinds of conditions that one needs to use to grow it are very well understood indeed. It is relatively tolerant of all sorts of conditions and you get an enormous volume of leaf out of each plant, one hectare of mature tobacco gives you 20,000 kilograms or 20 metric tons of wet leaf. So that is an enormous volume of plant material that you can actually make something out of."
What Rybicki and his team are trying to make out of tobacco is an affordable vaccine against the virus which causes cancer in the cervix, the gateway between the vagina and the uterus. (Men can transmit the virus. They can also develop cancer of the penis. However, men have a far lower rate of penile cancer, compared to cervical cancer in women, so it’s not quite the same public health issue.)
"You start with trying to make something that the immune system is going to recognise instead of the virus. You cannot use the live virus because you cannot culture these particular viruses, it is almost impossible," says the Zambia-born viral biotechnologist. "So what you do is make a portion of the virus - that is, the protein coat - which is what the immune system recognises. You can make this in a number of systems. And the nice thing about it is however you make it, it usually self-assembles - that is, it makes something that looks like the real virus. We can make it in animal cell cultures, we can make it in insect cell cultures, we can make it in plants. And we are trying to make plant production a reality."
The hollowed-out virus lacks nucleic acid, the trigger which makes the virus infectious. Consider a jacket or coat without anyone inhabiting it. It lies limp and flat. The same thing applies to this protein coat. Give a human the hollowed-out virus, with the outside intact, and the body’s immune system goes on attack. If the real virus shows up, transmitted by sex, it doesn’t stand a chance.
Plant vaccine factories
"The primary reason for making things like vaccines in plants is that it is potentially cheap," Rybicki said. "We may be able to cut costs by orders of magnitude, because you do not need a fermentation plant which you would for yeast or bacteria, you don't need huge tissue culture facilities which you would need for human or insect or animal tissue culture. What you need is a field or probably more likely a greenhouse."
The particles are also relatively easy to purify. They are "nice big stable particles, which cannot do anything except provoke a response."
Like any vaccine developers, the team is far from their goal – and relatively comfortable with that.
Vaccines that attack the virus not the wallet
"The usual vaccine production pathway from initiation of research to production is about 10 years and there is a lot of reiteration because you have to discover how to do things better or even how to do things at all," said Rybicki. "We are still in the development phase. We have got candidates, we know that we can make them. We need to make them on a bigger scale, prove that we can make them economically and then stick them in a bottle. Only then will we begin animal testing, let alone human testing."
South Africa used to have the capacity to generate its own polio virus vaccine in the 1950s. Now it imports. In his office at the Department of Molecular and Cell Biology, Rybicki notes that simply working on a vaccine carries significant advantages for developing countries: "there are a lot of orphan diseases out there that nobody wants to make a vaccine for. Vaccines cost about one hundred million US dollars to take through from beginning to human testing, just through to human testing, and this is enormous money for big pharmaceutical companies. Drug development can cost even more than vaccine development but because the vaccine market is so much smaller than the drug market, the return is relatively low."
The number of vaccines being made today has dropped to its lowest in a quarter of a century. Some vaccines have become a victim of their own success: a one-off dose of polio drops generates considerably less money than say, anti-depressant pills which have to be taken every day for the rest of the patient’s life.
But there are major international efforts underway in countries such as India, Brazil, China and Argentina to make publicly funded vaccines. "Diseases that don't occur in Europe or the United States do not get vaccines made for them. Or they don’t get the right type of vaccine. In Africa, we won’t necessarily get the correct HIV subtype vaccine made for example."
Also, new vaccines made in Europe or the US are expensive. "The Hepatitis B vaccine when it first came out was around 40$ a dose and it is now about a dollar a dose but it took ten or 15 years to get to that point!" marvelled Rybicki. The current push by big pharmaceutical companies for a vaccine for cervical cancer – already well advanced, with the first human trials accomplished - doesn’t worry him. The vaccine will be too expensive for third world health budgets, he predicts. His aim is to find something that attacks the virus, not the wallet.
Dr Ed Rybicki: firstname.lastname@example.org