UT Scientists Created an Effective Vaccine Candidate for a Dangerous Tropical Disease

An entomologist is observing an Aedes aegypti mosquito under a microscope. This mosquito species can spread dangerous diseases, such as Chikungunya, Zika, Dengue virus and yellow fever. Author: Flickr Creative Commons/Airman Magazine
An entomologist is observing an Aedes aegypti mosquito under a microscope. This mosquito species can spread dangerous diseases, such as Chikungunya, Zika, Dengue virus and yellow fever. Author: Flickr Creative Commons/Airman Magazine

The tropical Chikungunya fever, whose course is generally much more severe than that of viral Zika virus (ZIKV) infection, did not interest anyone until 2005. Then, however, massive outbreaks of Chikungunya virus (CHIKV) infection on islands in the Indian Ocean followed by extensive epidemics in India, Sri Lanka, Caribbean islands and Americas draw attention of scientist and the public to this mosquito-transmitted virus.

By now, relatively few pre-clinically evaluated vaccine candidates exist for preventing the CHIKV infection. One of these was developed by virologists from the Tartu University, who tested its effect in cooperation with scientists from Sweden, the United Kingdom, France, Germany, Spain, Australia and Singapore.

The preclinical trials with mice and monkeys have been completed. Monkey trials were led by French scientists and showed extraordinarily good results. The drug company is interested in moving the vaccine candidate into clinical (human) trials.

“The trouble is, we killed 28 monkeys to develop the Chikungunya vaccine candidate,” Andres Merits, Professor of Applied Virology at the University of Tartu, begins our conversation that was intended to reflect the success and productivity of his research. All animal studies represented inevitable part of research and were approved by the ethics committees. However, even monkey still remains a disease model. In this case, it represented certain trouble: none of the monkeys complained any joint pains or drowsiness during the trials. Merits chuckles, but it is a serious matter.

For many, including editors of scientific journals, it gives a good reason to question the effective vaccine candidate created in cooperation with the University of Tartu, “But how do we know your product is safe?” And correct they are – we don’t. At least not until it has not been clinically tested in humans.

Nevertheless, we are talking about the most recent and thorough research into a Chikungunya vaccine to date.

Whether this means that scientists have tied in the battle against Chikungunya which started a decade ago, or are they even in the lead, is to be shown by time and further development.

“We measured all possible molecular parameters associated with CHIKV symptoms including arthritis and other joint inflammations,” continues Merits to introduce research into the vaccine candidate against Chikungunya tested in monkeys.

The main body of the study was already completed in 2014, but was only published now, on 23 March, in the new prestigious American biomedicine journal JCI Insight.

“This scientific article is crammed with figures and diagrams that even I can’t make sense of any more to the finest detail (which is one of many reasons why international collaboration was critical), but these all confirm that none of the inflammation-related markers was increased in a vaccinated test animal.

This means that the vaccine candidate we developed, namely the rationally designed attenuated Chikungunya virus, does not cause inflammations in monkeys. However, we cannot guarantee that it won’t induce these – or any other side effects – in humans. Nobody knows!”

Will the candidate become a vaccine?

Now, Merits is hoping that their cooperation partner, an Austrian vaccine company Valneva, would take the vaccine candidate for Chikungunya, which was created in cooperation between eight laboratories, on to the clinical trials.

“Maybe such trials are already underway, but I cannot be certain. They have never reported it. This stage of vaccine development is very different form previous pre-clinical studies.”

The Austrians’ interest in the attenuated vaccine candidate that was originally designed and constructed at the University of Tartu and then analysed by an international team was a significant development, as the company invested tens of thousands of euros in completing the research, i.e., in testing the vaccine candidate in monkeys.

Professor Merits explains that preclinical trials are mainly used to check that the vaccine candidate does not cause severe side effects in animals and ensures permanent protection against the virus. Considering the unpredictable nature of CHIKV outbreaks, it is also highly preferable that permanent protection would be achieved after single administration, as it indeed was the case.

If the human trials start, a small group of 10–15 people will be involved in the first clinical stage. The aim of this stage is to estimate safety of the new vaccine. Though it is essential, it may not show much, because even very common side effects caused by modern vaccines typically occur only in one user in a hundred. Still, it is a big step forward and even if clinical trials have not been completed by the next epidemic outbreak, it can be helpful for suppressing a virus outbreak.

“A similar story happened with Ebola: at the time of the latest epidemic, the vaccine candidates that had reached nowhere were already there, sitting in the fridge. When used during an outbreak, they worked perfectly,” remembers Merits.

“WHO’s only big mistake was that vaccination wasn’t implemented immediately, when things took a bad turn. In the event of an epidemic like Ebola, complaints that the life-saving medicine has not passed all clinical trials are largely irrelevant. If you have faced the virus, you will unfortunately have to make big compromises on possible safety issues. If the technology works and you know that, at least, you won’t die of Ebola, you will use it.”

At this point, Merits refers to Bill Gates who has said that the world is not capable of discovering virus outbreaks quickly enough and responding to them fast enough.

Gates has said that scientists can be a lot faster and do no longer need to spend years or decades on creating a new vaccine: new DNA/RNA vaccines should be completed in less than a year, preferably in a few months. Regarding these comments, Merits argues that, actually, time spent on the development of an effective vaccine should indeed be shortened from 10 years to 90 days.

“For many viruses, it’s indeed not unreal, Gates knows what he is talking about. At least technology and science are ready to accept this challenge.”

The translation of this article from Estonian Public Broadcasting science news portal Novaator was funded by the European Regional Development Fund through Estonian Research Council.