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

Important results from the project

An intermediate goal was to produce subunit vaccines against SARS-CoV-2 based on recombinant spike protein linked to CpG-rich oligodeoxyribonucleotides using click chemistry, and to investigate whether carbohydrate structures on the spike protein regulate antibody binding. We produced a vaccine candidate and defined its ability to activate immune cells and antibody reactivity. Recombinant human surfactant protein D was evaluated for antiviral effect against SARS-CoV-2. Different concentrations were evaluated in neutralization tests and in binding experiments.

Expected long term effects

We were able to produce vaccine candidates based on the S1 domain of the spike protein directly linked to CpG-rich oligodeoxyribonucleotides. Furthermore, we showed that antibody reactivity to the spike protein is dependent on carbohydrate structures and that there is a potential to modulate the carbohydrates in order to enhance antibody reactivity. The results can form the basis for further development of subunit vaccines.

Approach and implementation

During the project, we encountered a number of difficulties. On the one hand, we had to shift the production of the recombinant S1 to an external party, which delayed the project. Furthermore, it proved more complicated to couple the recombinant protein to CpG-ON with sufficient efficiency and to establish which protein / oligo-conjugate was optimal for maintaining immunostimulatory effect. The problems were solved but with a delay of the project. In summary, the project plan was ambitious in relation to the stipulated schedule.