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Synthetic Biology Platform Designed for Vaccines

Imre Berger and Frédéric Garzoni

Imre Berger, right, and Frédéric Garzoni, founders of Imophoron (Unit DX)

26 Sept. 2019. Researchers in France and the U.K. developed a modular technology with synthetic and computational biology for designing vaccines against infectious diseases. A team from the French National Centre for Scientific Research (CNRS) in Grenoble and University of Bristol in the U.K. report their findings, including design of a vaccine against the virus Chikungunya, in yesterday’s issue of the journal Science Advances.

The researchers led by CNRS structural biologist and virologist Pascal Fender and Bristol biochemist and synthetic biologist Imre Berger are seeking tools for designing vaccines for infectious diseases that in recent years appear quickly, such as Zika and Ebola, leaving health authorities with few options for battling epidemics. In addition, many vaccines today need special shipping and handling, such as refrigeration from manufacture to administration to patients. The team is seeking solutions that make possible design of vaccines meeting special needs or with special properties.

Fender, Berger, and colleagues identified a set of vaccine properties that health authorities need today. Among those characteristics are an ability to provoke a strong immune response, safety for patients, produced with genetic engineering and still amenable to further engineering, available in large quantities, and without needing an adjuvant or supplement. The team also underscored the need for stability in fluctuating temperatures, meaning no need for refrigeration.

The researchers devised a platform for vaccine design around virus-like particles, which as the name implies, offer particles with elements similar enough to viruses to provoke an immune response, but not enough of the virus to cause disease. The particles in this case are derived from adenoviruses, benign viruses to most humans that are often used in gene therapies for their ability to penetrate cell nuclei and deliver genomic payloads.

The team calls this super virus-like particle an ADDomer. The ADDomer’s design is a result of intensive repeated calculations with large data sets using cloud computing facilities from IT/networking company Oracle. The result is a safe, virus-like particle structure down to near atomic resolution that acts as a delivery vehicle for vaccine proteins. The team designed the ADDomer with a modular plug-in structure, allowing insertion of various antigens to provoke specific immune responses.

But one feature of ADDomers stands out, their thermal stability. “We were working with a protein that forms a multimeric particle resembling a virus but is completely safe, because it has no genetic material inside,” says Fender in a University of Bristol statement. “Completely by chance, we discovered that this particle was incredibly stable even after months, without refrigeration.”

To prove the concept, the researchers designed a vaccine to prevent infections from Chikungunya viruses. Chikungunya is a disease from viruses carried by mosquitoes that results in symptoms similar to arthritis, such as joint pain and swelling, but also fever, headache, muscle pain, and rash that can persist for months or years. It’s prevalent in tropical regions, but in recent years spread to parts of North and South America.

The Chikungunya vaccine candidate adds a peptide, short chain of amino acids, called E2EP3 known to generate antibodies that reduce the viral load from the Chikungunya virus. Tests in lab cultures and mice show the ADDomer-based Chikungunya vaccine generates higher antibody concentrations in response in the vaccine.

Berger and co-author Frédéric Garzoni founded the company Imophoron Ltd. to develop and commercialize the ADDomer platform. The start-up company resides at Unit DX, a technology incubator in Bristol for new science-based enterprises.

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