Targeting the SARS-CoV-2 spike protein to achieve hyperimmunicity and reduce infectivity

Purpose and goal We intend to develop a new concept for producing vaccine candidates against SARS-CoV-2 based on the spike protein. By modulating the carbohydrate content of the spike protein and directly linking an adjuvant to the spike protein, we want to generate vaccine candidates with high immunogenicity. We will also evaluate the antiviral effect of surfactant protein D (SP-D). SP-D is a protein which is naturally occurring in the respiratory tract and has been shown to bind to the SARS-CoV-2 spike protein. We will evaluate whether SP-D prevents SARS-CoV-2 infection in cell culture. Expected results and effects A novel work flow for more rapid development of vaccines against emerging pathogens cannot be underestimated. The first project aim would add techniques to the existing toolbox for subunit vaccine invention which would benefit not only research but also the industry. The second aim has potentially direct impact on the ongoing SARS-CoV-2 outbreak where the needs for efficient antiviral drugs are acute, but since surfactant protein D (SP-D) is a natural component of the respiratory tract it is conceivable that it can have an impact on other respiratory pathogens as well. Planned approach and implementation Spike protein from SARS-CoV-2 will be produced in cell culture. CpG oligodeoxynucleotides will be linked directly to the Spike protein. The Spike protein will be mapped for carbohydrates and modulated for high immunogenicity. Vaccine candidates will be evaluated for immunogenicity in cell and mouse model. Recombinant SP-D will be produced in E. coli. Potential antiviral effect is evaluated by mixing SP-D with SARS-CoV-2 before inoculating the virus on cell cultures. The effect is measured with real-time PCR and plaque reduction experiments as well as viability experiments.