Steering of SARS-CoV-2 Spike to different APC receptors will polarize immune formation in mice to different types

The SARS-CoV-2 pandemic has to date resulted in almost 7 million deaths worldwide and a much higher number of hospitalizations. Thanks to a global collective dedication and understanding of the need, new and efficient vaccines were rapidly available on the market. However, two doses were needed for protective efficacy in large parts of the population, and we still have large uncertainties with respect to what type of immune responses would be the most relevant correlate of protection in different population groups. Here, we sought to characterize the immune responses elicited when steering the Spike antigen to selected receptors expressed on APCs. The aim was to describe the different types of immune responses associated with the selective APC steering. Further, we wanted to evaluate the induction of cross-reactive antibodies after vaccination of mice. We found that steering the antigen towards distinct APC receptors resulted in increased cellular and humoral responses. In addition, the elicited responses were polarized based on the specific APCs which was targeted and were readily characterized. Lastly, steering the different Spike variant antigens to MHCII expressing cells resulted in production of cross-reactive antibodies. Based on these findings, we conclude that the type of immune response initiated by APC targeted vaccination can be influenced by the choice of APC receptor ligand. This advantageous knowledge can be used to produce vaccines specifically tailored to match the immune response wanted in different population groups with different needs. In addition, APC targeted vaccines can also be used to induce production of cross-reactive antibodies.