Antibody specificities for protective immunity after Covid-19 vaccination (Antikroppsspecificitet för skyddande immunitet efter Covid-19 vaccinering)

It is not understood what type of response that will be needed for protection against SARS-CoV-2 after vaccination, but early evidence points to a key role for neutralizing antibodies targeting the spike protein. However, which epitopes on the spike protein that are critical are not known and neither the prospects of generating such antibodies with different vaccine types. In this proposal, we aim to perform an in-depth investigation of the antibodies elicited by two leading vaccine candidates (mRNA and nanoparticle vaccines) entering clinical trials this summer and ultimately determine the antibody specificities needed for protection. My lab is currently conducting preclinical testing of these vaccines in non-human primates prior to the phase I trial. While the costs for these studies including basic analyses are covered, I apply for funding here to be able to in-depth explore the antibody responses to define the intrinsic epitope hierarchy of the spike and link this to protection. The epitope specificities of the antibodies elicited by the two distinctly different vaccine platforms will be addressed. We will purify and evaluate the spike-specific B cells on a clonal level by sequencing the B cell receptors and by expression of monoclonal antibodies for characterization. Our work can ultimately provide critical information on correlates of protection and the immunological repertoires induced by the different vaccines to guide down-selection for clinical studies. Immunologi inom det medicinska området