Pascal Fender was working on developing a new nanoparticle-based vaccine platform when—fatefully—he forgot a sample in the pocket of his lab coat. When the French National Centre for Scientific Research virologist rediscovered the sample a few months later, electron microscopy revealed that the protein particles were still intact—a surprising result that may lead to a new class of shelf-stable synthetic vaccines. Now, a team of researchers including Fender has used these particles to make a vaccine against Chikungunya, and they’ve demonstrated that it is stable at temperatures up to 45 °C (Sci. Adv. 2019, DOI: 10.1126/sciadv.aaw2853). The new platform is a virus-like particle (VLP) derived from a strain of human adenovirus. Unlike a traditionally formulated vaccine, which contains a weakened form of a virus, a VLP contains no genetic material. Instead, viral proteins self-assemble around a hollow core; this means there are fewer safety concerns associated with VLP-based vaccines. “It kind of looks like a virus,” explains University of Bristol synthetic biologist Imre Berger, “but it’s not.” Berger, who directs the Bristol Synthetic Biology Research Centre, co-led the new work.
Berger’s team focused on developing the platform into a vaccine candidate for the Chikungunya virus, a mosquito-borne pathogen endemic to Africa and Asia that causes fevers and joint pain. Although symptoms generally improve within a week, Chikungunya is estimated to be fatal in 1 in 1,000 cases. There is no cure for the virus, which has spread to the Americas and Western Europe in recent years. There is also no approved vaccine against the virus, though there is another under development. French biotech firm Valneva received a US Food and Drug Administration fast-track designation for their Chikungunya vaccine candidate in late 2018.
The team inserted a Chikungunya epitope—the peptide that alerts the immune system to the virus’s presence—into their virus-like particles. In mice, the vaccine provoked a strong immune response. However, the vaccinated mice were not exposed to the virus, so it’s not yet clear whether it can prevent infection.
The VLP platform also has an unexpected benefit. The researchers were initially interested in its potential to make safe vaccines. But the team’s VLPs are unusually stable, even at high temperatures—as Fender discovered by accident. After they stumbled on this, they stored samples at room temperature for several weeks, froze and thawed the samples, then incubated them at 45 °C for an hour. Along the way, there was no loss of structural integrity. Other VLP-based vaccines, such as Gardasil, the human papilloma virus vaccine, require refrigeration. The need for an unbroken cold chain—from manufacture to transportation to storage—makes distributing vaccines to resource-poor areas particularly challenging.
The team is working on adapting the platform for more than 30 other vaccine candidates, including both human and livestock diseases. The platform can carry multiple epitopes; this functionality can be used to create vaccines that protect against several diseases often found in the same area. For example, the researchers could use it to develop a triple vaccine against Chikungunya, Zika, and Dengue, which are all carried by the same mosquito species. Co-infection of at least two of the three viruses has been found in sub-Saharan Africa, south and southeast Asia, and Latin America.
University of New Mexico vaccine researcher Kathryn Frietze says that the antibody responses of the mice to the vaccine candidate were “encouraging,” and that the multifunctionality and thermal stability of the VLP make it an attractive candidate. But she cautions that the work is still in early stages of development. Berger and his collaborators are excited to take it further, and have recently founded a start-up focused on taking the Chikungunya vaccine candidate through the regulatory process.
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