Two-month-old Mea Adele lies comfortably on her father’s lap at Tampere University’s Vaccine Research Center. Her family, who heard about the trial from a bulletin sent to their home by the Center, is participating in a study on a vaccine against infections caused by the pneumococcus bacteria.
“I am a nurse, so I know and understand that medicine cannot advance without research,” says Timo Murkka, Mea Adele’s father.
Murkka considers vaccinations a timely topic. His family has always taken vaccines for granted, but not everyone shares his positive attitude towards them.
“There have been measles epidemics in Finland, and every autumn many people still wonder whether it is worthwhile to get the influenza shot,” Murkka says.
Both Physician Coordinator Miia Virta, the principal investigator at the Tampere Vaccine Research Center, and Professor Timo Vesikari, the Director of the Center, are paediatricians. Virta began working in vaccine research because she saw that the field creates wide-ranging benefits.
“In addition to clean water, hygiene, nutrition and antibiotics, vaccines are one of the most significant things that make people live longer,” Virta points out.
When in the future Mea Adele brings her own children to be vaccinated, they may get shots against diabetes and the norovirus, among others.
Enteroviruses cause common ailments familiar to all families with children. There are several types of enteroviruses, which are highly contagious and often make all members of the family ill. Moreover, they may have serious consequences.
Heikki Hyöty is professor of virology at Tampere University. Over thirty years ago, his research group started to analyse how viruses and microbes affect the immune system and autoimmune diseases, such as type 1 diabetes. The researchers realised that certain enteroviruses, combined with predisposing hereditary factors, were associated with a heightened risk of type 1 diabetes. Other international studies have also produced similar findings.
The lengthy research process identified certain types of virus, and an experimental vaccine was developed against them; it proved to be effective in mice.
A vaccine for humans is currently being manufactured in the Netherlands according to the specifications of the medical authorities. The vaccine will begin human testing in Finland in 2020.
“It is hugely important that we prevent diabetes – either with this vaccine or in some other way. There is no cure or means of preventing type 1 diabetes, and despite daily insulin shots, it increases the risk of comorbidity and reduces life expectancy,” Hyöty says.
The researchers estimated that at least half of new diabetes cases could be prevented. The vaccine is also expected to have a significant impact on public health in another way. Curbing the most common enteroviruses would prevent numerous acute infections, reduce sick leave and put a stop to serious complications.
The researchers’ aim is to make the vaccine a part of the National Immunisation Programme. Wide-ranging genetic studies on new-borns have shown that the autoimmune process, which destroys the insulin-producing beta cells in the pancreas, starts as early as 12–18 months in a great number of diabetics. This means that children are exposed to an outside trigger that instigates the disease – such as an enterovirus – at an early age, which is why the vaccine should be administered to babies.
The development of the diabetes vaccine has already been aided by the fact that the National Immunisation Programme already includes a vaccine against an enterovirus.
“Polio is also an enterovirus. The polio vaccine is one of the safest and most efficient vaccines ever developed,” Hyöty points out.
The polio vaccine includes three strands of enteroviruses: polio 1, 2 and 3. The vaccine is administered in three different shots before the age of six months. The diabetes vaccine would be given in a similar manner.
“Such a strategy would help us prevent even the first infections and give children protection against the start of the diabetes process,” Hyöty says.
In addition to flu-like symptoms and fever, enteroviruses cause hand, mouth and foot disease, rashes and ear infections. The virus can also cause serious illnesses, such as meningitis, myocarditis and paralysis.
Certain enteroviral infections may trigger type 1 diabetes in children with a hereditary genetic mutation predisposing to the disease. During the infection, the enterovirus affects the pancreas and destroys its cells. While final conclusive evidence about the role of enteroviruses in the development of some cases of diabetes has yet to be found, the vaccine development is seeking to confirm this causation.
Every year in Finland, approximately 500 under 15-year-olds and 1,500 over 15-year-olds develop type 1 diabetes. A functioning vaccine is likely to reduce these figures by half.
At the moment, there is no way to prevent type 1 diabetes, and there is no cure. Those suffering from the disease require a daily dose of insulin for the rest of their lives.
Tampere University has also developed another promising vaccine that is now entering the clinical testing phase. Head of Laboratory Vesna Blazevic, Professor Vesikari, and their research group have developed a new-generation protein vaccine to combat noroviruses and rotaviruses that cause vomiting and diarrhoea.
Blazevic points out that their protein vaccine does not contain an actual virus, but instead particles that imitate the norovirus and the VP6 protein that is found in the rotavirus.
“Our vaccine has never been in contact with the virus, which makes it very safe and tolerable for all. Our findings also support the idea that the norovirus and rotavirus shots should be given to children at the same time,” Blazevic says.
There is already a vaccine against the rotavirus, which is given to children as a part of the National Immunisation Programme. However, there is no vaccine against noroviruses.
Noroviruses and rotaviruses occur across the world and cause acute gastroenteritis.
“Globally, as much as 35% of lethal stomach conditions and cases of acute diarrhoea in children under the age of five are caused by rotaviruses and noroviruses,” Blazevic points out.
In Finland, most acute gastroenteritis infections that require hospital treatment are caused by the norovirus.
These viruses may also be dangerous for old people. Norovirus epidemics break out in elderly care facilities where they may be lethal, even in developed countries.
The norovirus-rotavirus vaccine developed by the Vaccine Research Center seems very promising. The Nature Medicine journal and the World Health Organization’s website mentions it as one of the three best vaccines being developed to combat noroviruses. At present, the Vaccine Research Center is looking to cooperate with a pharmaceutical company to start producing the vaccine.
According to Blazevic, the vaccine would be needed by children under two years old and people in care facilities, the army and schools – places where stomach bugs spread fast. Members of the public have also contacted the researchers.
“Many abhor vomiting and would be very happy to have a vaccine to protect against the norovirus,” Blazevic says.
The first vaccine was developed in 1796, when doctor and scientist Edward Jenner discovered that cowpox protected patients against the dangerous smallpox virus. His method was quickly adopted everywhere in the world. In Finland, immunisation against smallpox began in 1802. Vaccinations against smallpox ended in the 1980s when the World Health Organization declared the disease completely eradicated.
“The development of vaccines started from the more fatal illnesses. Vaccines have helped to get rid of many lethal contagious diseases that used to kill and maim people,” Hyöty says.
“As things are going, it looks likely that vaccines will be increasingly used to prevent more diseases,” Hyöty continues. In the past fifteen years, vaccine research has grown faster than any other field of medicine.
Vesikari agrees that the natural course of research is to concentrate on the prevention of diseases. Furthermore, better vaccines are also needed for diseases against which a vaccine already exists.
“For example, it would be important to curb influenza, but so far there has been no breakthrough discovery to find a ‘generally applicable’ vaccine that would prevent all influenza viruses,” Vesikari says.
According to Vesikari, there is one clear gap in the National Immunisation Programme in Finland.
“A vaccine against hepatitis B is not a part of the programme, even though the World Health Organization recommends everyone be immunised against the disease,” Vesikari points out.
At the moment, cutting-edge technology in vaccine development includes vaccines grown in plants. The Vaccine Research Center is currently working on a vegetable-based influenza vaccine that studies have shown to be as efficient as or even better than the egg-based influenza vaccines currently in use.
“A vegetable-based vaccine is also safer, because it can be given to people who are allergic to eggs,” Vesikari says.
In this case, the vaccine is grown in a plant of the tobacco family that does well in greenhouses.
The technology that makes the vegetable cell produce the virus may become a larger trend in vaccine research in the near future.
“It is likely that we can make other vaccines with this technique, too,” Vesikari adds.
In Finland, Tampere University’s Vaccine Research Center conducts the majority of Finnish clinical vaccine trials – i.e. trials involving human subjects. Trials are also conducted at several clinics across Finland.
In addition to engaging in research on new vaccines, the Vaccine Research Center develops its own vaccines, such as the norovirus-rotavirus vaccine.
The Center’s most recent major achievements include research into two meningococcus B vaccines that led to the registration of these vaccines and an extensive study on a herpes zoster vaccine that resulted in an EU sales licence.
The development of vaccine technologies has enabled the addition of several active ingredients to the same vaccine. In other words, one injection may protect against more than one disease. There may be as many as ten ingredients in a single vaccine.
Completely different viruses and microbes may be added; at present, a vaccine solution with six different viruses is being used.
In principle, there is no limit to how many vaccinations a person can take. For example, people take influenza shots annually. Hyöty believes that the limits come from the development costs.
“The development of vaccines is a very closely regulated branch of pharmaceutical development, which is time-consuming and technologically challenging. These aspects have an impact on the future of vaccine development,” Hyöty says.
Professor Vesikari also says that the business interests of the pharmaceutical industry have an impact on the development work.
“Even though medical research is concentrating on the prevention of diseases, does the pharmaceutical industry share this outlook?” Vesikari asks.
“It might take just one or two shots to prevent some disease, whereas treating the disease may require a lot of expensive medication,” Vesikari adds.
In some cases, business and medical interests are in direct conflict. According to Vesikari, the cost of a vaccine is picked up by wealthy western countries whereas vaccines delivered to low-income countries are cheaper and often supported by international sponsors. Both market niches are needed.
“It is clear that nothing will happen if the pharmaceutical companies do not recoup the money they have invested in the market,” Vesikari points out.
A virus is a parasite. In order for a virus to infect a host, it needs to attach itself to a receptor molecule of a cell in the host’s body. If it succeeds in doing this, the virus colonises the cell and harnesses the cell’s functions for its own purposes.
Within a day or two, the infected cell produces hundreds of thousands of new mini-viruses that spread throughout the body and seek out new cells to colonise.
Vaccines often contain an inactivated (i.e. dead) virus. The inactivated virus resembles the real virus, but it is unable to infect the patient. Structural parts of viruses and weakened viruses are also used in vaccines.
After the shot, the vaccine solution stays in the site of the injection. From there, it spreads to local lymph nodes and causes a strong reaction, which activates the production of antigens against the virus.
The vaccinated person develops an immune response, which stops the virus from attaching to the body. For example, in a vaccine against the enterovirus, the antigen molecules cover the cells, preventing the virus from attaching.