Purer vaccines grown in plants

The Vaccine Research Center directed by Professor Timo Vesikari is engaged in several clinical trials in addition to conducting its own scientific research. The Center’s latest breakthrough is a combination vaccine against the norovirus and the rotavirus, which cause diarrhoea in children.

The Vaccine Research Center directed by Professor Timo Vesikari is engaged in several clinical trials in addition to conducting its own scientific research. The Center’s latest breakthrough is a combination vaccine against the norovirus and the rotavirus, which cause diarrhoea in children.

The development of vaccines will increase in the future because antibiotic-resistant bacteria are making diseases harder to treat.

In the future, vaccines may be produced in plants, and vaccines grown in this manner may be purer and safer than current vaccines. Lower production costs present a further advantage of this technique.

“Plants can be used to produce large amounts of vaccine proteins, and the plant proteins can be filtered out reasonably well,” says Professor Timo Vesikari, director of the Vaccine Research Center at the University of Tampere.

However, even if some plant protein residues remained in a vaccine, they would cause no harm.

“Plants may be the way forward in vaccine production, and that will be the focus of our research,” Vesikari explains.

The cells of plants can be used to produce vaccine substances. The plants, which are cultivated in large greenhouses, are infected with various types of genetically modified viruses in order to produce the viruses’ proteins. Bacteria are added to facilitate the process, and at the final stage, the leaves of the plant are harvested and the virus protein is extracted and cleansed. Thus far, vaccines have been grown in a number of different species, including potato, corn and tobacco plants.

The purity of the plant-based vaccines is due to the fact that only one particular protein can be produced in the plant. For example, when an influenza vaccine is produced, the plants only produce a certain influenza protein. Thus, the vaccine does not contain the other potentially harmful parts of the virus.

The Vaccine Research Center recently developed a combination vaccine against the norovirus and the rotavirus, which cause diarrhoea in children. The researchers hope to produce the vaccine in plants in the future, and talks are currently underway with a Japanese partner. A successful outcome to the negotiations would mean that the vaccine would be produced in plants and the eventual clinical testing would be conducted at the Vaccine Research Center’s trial clinics in Finland.

Vaccines are increasingly being produced in cell cultures. For example, the influenza vaccine is produced in chicken eggs. Eggs are used to produce the whole virus, which is then broken down and purified. Vesikari mentions the Pandemrix vaccine against swine flu, which caused narcolepsy in some young Finnish patients. According to Vesikari, that vaccine was relatively impure.

“The new studies on Pandemrix, conducted by Outi Vaarala’s research group at the National Institute for Health and Welfare, are illuminating. The vaccine contained a relatively rough, broken virus with antigens other than those that were strictly necessary to prevent swine flu,” Vesikari says.

Furthermore, the vaccine contained a powerful adjuvant – an auxiliary substance. The combination of these two compounds seems to explain why some children and adolescents fell ill with narcolepsy. Such a side effect has never occurred before with any other vaccine.

A plant-based vaccine against seasonal influenza was presented at a scientific conference in Portugal this autumn.

The World Health Organization has also noted plant-based vaccines as the potential future of medicine, but the technical challenges of producing such vaccines must be solved first before they can be used on a larger scale.

As people become increasingly aware of antibiotic-resistant super bacteria, the demand to develop new vaccines will increase.

For example, a vaccine has been developed against the clostridium difficile bacterium, which causes a hospital-acquired infection. Trials of this vaccine are currently underway at the Vaccine Research Center’s ten trial clinics.

This life-threatening infection causes diarrhoea and inflammation of the colon, and it can generally be treated with antibiotics. However, while antibiotics work in most cases, difficult cases may prove lethal.

“It is an interesting new idea that efforts are made to prevent hospital-acquired bacteria with vaccines rather than antibiotics,” Vesikari notes.

The same treatment option is also being investigated and developed to fight other bacteria that cause hospital infections.

“I think more new vaccines against hospital-acquired infections will soon reach the trial phase,” Vesikari adds.

Vaccine development is also making other inroads in addition to battling infectious diseases. A vaccine against tobacco addiction is already under development.

“It is perfectly conceivable that one day we will immunise people against smoking at our clinics,” Vesikari says.

“We can also think about what other addictions could potentially be treated or prevented with vaccines, either by causing the patient to feel really ill or by preventing the euphoria induced by the abused substance.”

There is fierce global competition in the field of conducting clinical trials of new vaccines on people. All well-established universities capable of developing vaccines in the United States and Europe are participating in this race.

The Vaccine Research Center invests the money earned from such trials on scientific research, which has resulted in, among other things, the development of the norovirus-rotavirus combination vaccine.

“There used to be a time when people wrinkled their noses at the idea of a university or another academic institution engaged in commercial cooperation on clinical trials. The reality today is that everyone really wants to conduct such trials,” Vesikari says.

Some clinical vaccine trials have also generated scientific breakthroughs. Vesikari is especially happy because two vaccines against the meningococcus B bacterium, which causes meningitis, were registered and introduced worldwide this year. Preventing a disease that is very harmful to children and adolescents warms the heart of this former paediatrician.

“It is very important that we are now able to prevent the last remaining major cause of meningitis in children and adolescents,” he says.

At present, vaccine research is spreading to an ever-increasing number of countries. Vaccine manufacturers want to conduct research closer to their largest markets. Finland is a small market and cannot compete in terms of volume, but Vesikari is conscious of the Vaccine Research Center’s strengths.

“Our assets at the Vaccine Research Center are high quality, experience and the present network of ten trial clinics. This means we are always prepared to take on new projects.”

Text: Tiina Lankinen
Photograph: Jonne Renvall

Vaccine Research Center