In research shared by the University of Bristol in November 2023, a team demonstrates the validity of nature-inspired nanoparticle-based reagents using an approach that combined “synthetic, computational, and structural methods” with “in vitro antibdody selection and in vivo immunisation”. The paper, in Antibody Therapeutics, suggests that Imophoron’s Adenovirus-derived dodecamer (ADDomer)-based nanoparticles can be effectively used in active and passive immunisation. Furthermore, the team states that this research “provides a blueprint for crafting reagents to combat respiratory viral infections”.
ADDomer technology
The researchers recall that “shortly before” the start of the COVID-19 pandemic, they introduce Adenovirus-derived dodecamer (ADDomer); this is a “synthetic self-assembling protein nanoparticle platform for highly efficient vaccination by genetically encoded multiepitope display”. It “derives from a single protein component” of adenovirus, which “forms pentons at the vertices of the viral capsid” to provide a “base for the attachment of the adenoviral fibre”.
“When produced recombinantly in isolation, 60 copies of this penton-base protomer spontaneously self-assemble in the test-tube into a dodecahedron comprising 12 pentons.”
ADDomer can be stable over 50°C and stored at ambient temperature for prolonged periods; this suggests that ADDomer-based vaccines and therapeutics could be “potentially produced, stored, and transported” without requiring refrigeration.
Study goals
The study aim was to develop a thermostable ADDomer-based COVID-19 vaccine that could overcome “limitations associated with the cold-chain challenge” but maintain the advantages offered by the technology. The vaccine, ADDoCoV, was validated by near-atomic resolution electron cryo-microscopy (cryo-EM) and molecular dynamics (MD) in a “hybrid approach”.
To confirm “authenticity and accessibility of the displayed immunogenic epitopes” the team deployed Ribosome Display. Furthermore, the “prowess” of the ADDoCoV design was demonstrated by the immunisation of mice to elicit antigen-specific IgA and IgG antibody responses and the induction of mucosal immune responses.
Pandemic preparedness
Professor Imre Berge of the University of Bristol reflected that the COVID-19 pandemic “reminds us of the critical importance of being prepared” as well as the need for “innovative approaches” to accelerate and ameliorate vaccine development.
“Our study demonstrates the use of ADDomer-based nanoparticles in active and passive immunisation and provides a blueprint for developing reagents and vaccines to tackle respiratory infections.”
Chief Executive of Imophoron, Richard Bungay, commented that the “important” paper highlights the “significant” potential of the company’s “unique’ platforms in developing “novel, thermostable vaccines to combat infectious diseases”.
“The research represents a significant milestone for our team of world-class scientists, in collaboration with the excellent team at the University of Bristol, in our ongoing commitment to advancing global health.”
To understand the technology in greater detail, head to Imophoron’s website or check out the paper here. For more on vaccine technology and infectious diseases, why not subscribe to our weekly newsletters here?
