Controlled human infection models for influenza and chikungungya

‘Our controlled human infection models allow us to evaluate vaccines and treatments,’ says Ingrid de Visser-Kamerling, Research Director of Infectious Diseases. Both nationally and internationally, the Infectious Diseases group contributes to the development of vaccines and therapies, focusing on innovative approaches to combat various infectious diseases. In the Netherlands, these activities are part of the InFECT-NL consortium. Internationally, CHDR participates in the INNO4VAC consortium, for which De Visser and her team organised the stakeholders symposium in 2024.
Within another European consortium called FLUniversal, the team aims to contribute to the clinical development of a universal influenza vaccine. Influenza viruses mutate rapidly, requiring a new vaccine every year. These seasonal vaccines are aimed at the antigenic variants of the strains that are predicted to be common in the next influenza season. However, given the six-month production timeline, these vaccines often prove less effective against some circulating variants. The FLUniversal project is developing a vaccine effective against all influenza A and B variants. Additionally, this approach would enhance production efficiency, eliminating the need for the hundreds of millions of eggs currently used annually in vaccine production.

CHDR is currently establishing a controlled human infection model (CHIM) for influenza. De Visser explains that preparations for this initiative have been highly complex and labor-intensive. The plan is to import the H3N2 influenza virus from the US National Institutes of Health (NIH). The virus is a wild-type reconstructed by reverse genetics. De Visser: ‘The major advantage of this approach is that the exact same virus can consistently produced under GMP conditions. To complicate matters however, European Union regulations consider this virus to be a genetically modified organism, even though it is identical to wildtype virus. Over the past few months, ’ve gained even more insight into the regulatory landscape, and it looks like we’ll be able to conduct our first study in 2025.’ Similar to the rhinovirus model implemented this year, this first influenza study aims to just implement the CHIM without additional interventions. Once successfully implemented, the model will be used in vaccine development studies.

CHDR is also preparing to establish a controlled human infection model for chikungunya, a mosquito-borne arbovirus prevalent in Africa, Asia, and South America. Chikungunya can cause debilitating chronic symptoms, including arthritis, and in rare cases, can be life-threatening. De Visser: ‘The disabilities caused by the chikungungya virus can have major consequences for patients, as they may become significantly less productive. Chikungungya therefore has a major impact, and the virus is spreading around the world.'

Infecting study participants with a virus that causes a chronic disease is obviously unethical. The CHIM that is set up for this disease will therefore be based on an attenuated virus. This is a strain approved by the European Medicines Agency as a vaccine against chikungungya. De Visser: ‘It may seem paradoxical that we are essentially administering a vaccine to our study participants. However, our objective is to develop a model that demonstrates viraemia. This will allow us to test the effectiveness of treatments that prevent viraemia. The use of an attenuated virus provides a safe approach for establishing a CHIM for chikungunya. Fighting infections in both developed and developing countries remains a key priority for CHDR and for Prof Meta Roestenberg with whom we perfom all these studies.'