Development of an elastin-like peptide based theranostic platform technology to fight SARS-CoV-2
A protein-based nanoparticle with multivalent display of targeted nanobodies blocking SARS-CoV-2 infection effectively
During the outbreak of SARS-CoV-2 pandemic, an urgent need arose for effective virus-specific therapeutics. In this project we developed an immuno- nanoparticle-based platform using elastin-like polypeptides (ELPs) targeting spike proteins from SARS-CoV-2. The project combined the ELP nanoparticle engineering technology from Eindhoven University of Technology, targeting technologies from the Radboud university medical center and nanobodies from Talem Therapeutics.
SARS-CoV-2 is highly transmissible, leading to widespread global infections and causing millions of deaths. The course of a SARS-CoV-2 infection ranges from asymptomatic or mild symptoms to severe symptoms leading to lung and other organ complications that require hospitalization. Recently, several variants have emerged, some with increased transmissibility and/or the ability to escape from vaccines. There is a certain need for developing an efficient therapeutic platform to tackle this hurdle as well as for prevention in future pandemics.
Our solution is was to develop an immuno-nanoparticle using ELPs, which are based on proteins that can spontaneously form micelles upon thermal triggers. Targeted nanobodies of choice were genetically fused to ELPs and expressed easily from E.coli. Immuno-nanoparticles were prepared by mixing ELP with nanobody-ELPs at certain ratios to control the multivalency. Once encountering SARS-CoV-2 virus, targeted nanobodies bind effectively to spike proteins; furthermore, with multivalent display they co-form clusters and thus prevent viral infection. The clusters could be further taken up by macrophages, a first step towards a vaccination effect.
This plug and play immuno platforms allowed us to engineer (1) numbers of displayed nanobodies and (2) the choice of nanobodies for neutralizing effectively various SARS-CoV-2 variants. Compared to a single nanobody which failed to neutralize, the multivalent displays, by the ELP, showed significant improvement in neutralization with similar efficacy as commercial antibodies. The ELP platform could be further modified to meet the conditions of newer variants and/or new viruses in the future.
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