Chikungunya model ready for testing vaccines and antivirals

The chikungunya virus is an RNA virus transmitted by mosquitoes. Originally from Africa, the virus is now also found in Asia, South and Central America and the United States. Its range is expected to increase further due to climate change. ‘Due to the increased focus on pandemic preparedness, there is growing interest in this virus,’ says Dr Ingrid de Visser-Kamerling, Research Director Infectious Diseases. ‘I’m very glad that we now have an effective controlled human infection model that we can use to investigate vaccines and therapeutics.’

De Visser and her collaborators in the research group of Prof. Meta Roestenberg at Leiden University Medical Center (LUMC) are working on controlled human infection models, CHIMs, in which healthy study participants are deliberately infected. ‘With some pathogens, such as the RS virus, we can do this safely because the symptoms are mild and self-limiting,’ says De Visser. ‘The problem with the chikungunya virus is that it causes chronic joint pains in a relatively large number of people. So, infection of healthy participants with the virus itself is not an option.’

Luckily, a vaccine against chikungunya came on the market in early 2025, which is a live-attenuated variant of the virus. ‘It has been approved as a vaccine, so was found to be safe. Additionally, we have thoroughly verified its safety profile,’ says De Visser. There were indications in the literature that the attenuated virus replicated in the body causing viremia, but this had not yet been systematically investigated.

Funded by the CHDR research fund, Clinical Scientist Victor Cnossen conducted the study, administering the chikungunya vaccine to 12 healthy study participants. The study could be conducted on an outpatient basis. After all, people who receive the chikungunya vaccine because of a trip to the tropics don’t have to take special safety measures either. Systematic follow-up in the days after administration showed that a significant proportion of the participants did indeed develop viremia, meaning that this vaccine could be used as a so-called challenge agent. Some participants also had transient mild symptoms such as joint and muscle pain. At the last follow-up moment 28 days after the moment of administering the vaccine, all participants were completely symptom-free.

The chikungunya CHIM can be used to test medicines or new vaccines. De Visser: ‘We would administer the new medicine or vaccine and then the registered live-attenuated chikungunya vaccine as challenge agent, to see whether the new intervention protects the participant against viremia and symptoms. At first, it seems a bit counterintuitive to use a vaccine as an infection model, but once we explain the concept, people become enthusiastic.’

Shortly after the results were processed, De Visser participated in an international panel of infectious disease experts in Oxford. ‘One of the other speakers philosophised about the possibility of setting up a CHIM for chikungunya, and he lamented the fact that there were no systematic data on the viremia caused by the attenuated virus. I immediately sent a text message to Victor, and minutes later he had sent me a slide with our results, showing the exact course of the viremia in the days after vaccination. This immediately attracted the interest of a start-up company that is developing a new chikungunya vaccine. So, it looks like we will soon be able to use our model in a sponsored study’.